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  • 1995-1999  (957)
  • 1999  (957)
  • General Chemistry  (750)
  • breast cancer  (126)
  • chemotherapy  (86)
  • Engineering
  • Nuclear reactions
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Years
  • 1995-1999  (957)
Year
Keywords
  • 1
    Electronic Resource
    Electronic Resource
    Effects of experimental chemoendocrine therapy with a combination of a pure antiestrogen and 5-fluorouracil on human breast cancer cells implanted in nude mice (1999)
    Springer
    Surgery today 29 (1999), S. 149-156 
    Details
    ISSN: 1436-2813
    Keywords: chemoendocrine therapy ; pure antiestrogen ; 5-fluorouracil ; nude mouse ; breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The antitumor effects of an experimental chemoendocrine therapy combining a new pure antiestrogen ICI 182780 and 5-fluorouracil (5-FU) were studied on MCF-7 human breast cancer cells implanted in nude mice. ICI 182780 had a dose-dependent antitumor activity, which was potentiated by the concomitant use of 5-FU. When compared with the control group, the estrogen receptor (ER) level in the ICI 182780 group was lower and that in the combination group was markedly lower. Cell cycle analysis by flow cytometry (FCM) resulted in a lower percentage of S-phase cells (%S) in the treated mice. No significant difference was observed in the 5-FU concentrations in tumor cells, while the 5-FU content in RNA was significantly higher in the combination group. The changes in free thymidylate synthetase (TS) concentration indicated TS synthesis after the administration of 5-FU to be more greatly suppressed in the combination group than in the 5-FU group. These results suggest that ICI 182780 and 5-FU exert their combination effect mainly on ER-positive cells, and that the suppression of TS synthesis in tumor cells and the potentiation of the 5-FU-induced metabolic dysfunction of RNA are thus involved in the mode of action of this combination therapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02482240
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  • 2
    Electronic Resource
    Electronic Resource
    The effectiveness of chemotherapy with cisplatin and 5-fluorouracil for recurrent small cell neuroendocrine carcinoma of the rectum: Report of a case (1999)
    Springer
    Surgery today 29 (1999), S. 165-169 
    Details
    ISSN: 1436-2813
    Keywords: small cell neuroendocrine carcinoma ; colorectum ; chemotherapy ; cisplatin ; 5-fluorouracil
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We report herein the case of a 46-year-old-man with small cell neuroendocrine carcinoma (NEC) concomitant with large villous adenoma of the rectum, who underwent abdominaoperineal resection with regional lymphnode dissection. The resected specimen was histologically found to contain a small lesion of NEC confined to the submucosa in the large adenoma. A computed tomography scan done 4 months postoperatively revealed recurrences in the liver, lymph nodes, and bone. Therefore, two cycles of sequential intravenous combined chemotherapy with standard doses of cisplatin and 5-fluorouracil (5-FU) were administered, after which the size of each tumor decreased remarkably. Nevertheless, the patient died 8 months after the operation. As there was a fair response of this tumor to the combined chemotherapy of cisplatin and 5-FU, this regimen against NEC of the colon and rectum should be given consideration.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02482243
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  • 3
    Electronic Resource
    Electronic Resource
    Recent advances in the treatment of prostate cancer (1999)
    Springer
    Annals of oncology 10 (1999), S. 891-898 
    Details
    ISSN: 1569-8041
    Keywords: brachytherapy ; chemotherapy ; hormonal therapy ; prostate cancer ; recent advances
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract As new evidence for prostate cancer treatment has emerged in the last few years, longstanding controversies in the treatment of prostate cancer have resurfaced. A number of long-held tenets of prostate cancer therapy have been revisited, sometimes with surprising and challenging results. Although neoadjuvant hormonal therapy prior to radical prostatectomy decreases positive surgical margin rates, longer follow-up is needed to support survival improvement of this combined modality therapy. Androgen deprivation combined with radiation therapy appears to improve disease-free survival (and survival in one series) in patients with locally advanced cancer. Another approach to locally advanced prostate cancer using three-dimensional conformal radiation therapy may improve long term outcome. The data are currently insufficient to conclude that interstitial low dose rate brachytherapy is equivalent to conventional treatments: patients with small tumor volumes and low Gleason grade seem to obtain more benefit, whereas for large tumors with higher gleason grades this approach seems inferior to conventional treatments. In advanced prostate cancer recent data suggest that immediate hormonal therapy improves survival. In this group of patients the use of maximum androgen blockade remains controversial but may adversely affect quality of life compared to orchiectomy alone. Intermittent hormonal therapy may improve quality of life, although effect upon survival is unknown. Chemotherapy in combination with androgen deprivation is currently being studied as front-line therapy in advanced prostate cancer. Palliative benefit of chemotherapy for hormone refractory prostate cancer remains an important endpoint; survival advantage has not been seen in any randomized trials. Suramin may delay disease progression in hormone refractory prostate cancer. Many aspects of prostate cancer treatment will remain controversial until results of large, randomized trials with longer follow-up are available.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008385607847
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  • 4
    Electronic Resource
    Electronic Resource
    Daily times four vinorelbine plus cisplatin in advanced non-small-cell lung cancer: A phase II trial of a novel schedule (1999)
    Springer
    Annals of oncology 10 (1999), S. 989-991 
    Details
    ISSN: 1569-8041
    Keywords: chemotherapy ; multiday vinorelbine–cisplatin ; NSCLC
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: To evaluate the efficacy of a novel multiday schedule of vinorelbine and cisplatin in patients with advanced NSCLC. Patients and methods: Thirty patients were enrolled, including 27 patients with stage IV disease, and 11 patients with performance status of 2. They received a maximum of four chemotherapy cycles with cisplatin 20 mg/m2/day and vinorelbine 15 mg/m2/day intravenously (i.v.) for four consecutive days, every three weeks, with prophylactic filgrastim. Results: Sixteen patients responded (53%, 95% confidence interval (95% CI): 34%–72%), including two complete and fourteen partial confirmed responses. Median survival for all patients was 8.1 months, with actuarial one-year and two-year survival rates of 40% and 15%. Despite prophylactic filgrastim, the delivered vinorelbine dose intensity of 16.8 mg/m2/week caused febrile neutropenia in 48% of patients (16% of cycles), resulting in one treatment-related death. Common nonhematologic toxicities included delayed emesis, asthenia, and constipation. Conclusions: This multiday vinorelbine–cisplatin schedule is highly active against advanced NSCLC but results in frequent neutropenic complications. The myelotoxicity and antitumor efficacy of vinorelbine in NSCLC patients may be schedule-dependent.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008355504913
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  • 5
    Electronic Resource
    Electronic Resource
    Chop Versus Macop-b in Aggressive Lymphoma – a Nordic Lymphoma Group Randomised Trial (1999)
    Springer
    Annals of oncology 10 (1999), S. 1079-1086 
    Details
    ISSN: 1569-8041
    Keywords: aggressive lymphoma ; chemotherapy ; prognostic factors ; randomised trial
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: The long-term survival of patients with advanced stage aggressive lymphoma has not improved significantly during the last twenty years. In a randomised trial, the efficacy of MACOP-B, a six-drug weekly chemotherapy regimen, was compared to CHOP, the current standard regimen, in terms of overall and failure-free survival, toxicity and health related quality of life. Patients and methods: Four hundred five patients with aggressive lymphoma, stage II–IV, age 18–67, were randomised to receive either 12 weeks of MACOP-B or 8 courses of CHOP over 24 weeks. Special emphasis was put in the definition of Ann Arbor stage in extranodal disease. A subset of 95 patients also entered a quality of life study, based on the EORTC QLQ-C30. Results: Thirty-one patients were ineligible. Among the remaining 374 patients, the median age was 52 years. According to the age-adjusted International Prognostic Index, 37% were ‘high-intermediate’ or ‘high-risk’ patients. No difference could be demonstrated, either in overall survival (60% at five years in the MACOP-B group and 59% in the CHOP group) or in failure-free survival (47% at five years with MACOP-B and 44% with CHOP). In terms of quality of life, physical function and global quality of life were more impaired in patients receiving MACOP-B, who also exhibited more non-haematological toxicity. Conclusion: No superiority of MACOP-B compared to CHOP could be demonstrated. CHOP remains the treatment of choice in low-risk patients. At present, intensified or experimental treatment should be reserved for high-risk disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008392528248
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  • 6
    Electronic Resource
    Electronic Resource
    Paclitaxel, ifosfamide and cisplatin (TIP) chemotherapy for recurrent or persistent squamous-cell cervical cancer (1999)
    Springer
    Annals of oncology 10 (1999), S. 1171-1174 
    Details
    ISSN: 1569-8041
    Keywords: cervical cancer ; chemotherapy ; cisplatin ; ifosfamide ; paclitaxel ; survival
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: The results of salvage chemotherapy for recurrent or persistent squamous-cell cervical cancer are unsatisfactory. Cisplatin and Ifosfamide are effective compounds in cervical cancer. Paclitaxel has recently been tested with promising results. The aim of this study was to assess the efficacy of a combination of paclitaxel, ifosfamide and cisplatin (TIP) for persistent/recurrent squamous-cell cervical carcinoma in a phase II trial. Patients and methods: Forty-five women were treated with the TIP regimen. Thirty-one had received prior irradiation. Paclitaxel was given at a dose of 175 mg/m2, ifosfamide at a dose of 5 g/m2, and cisplatin at a dose of 75 mg/m2 (50 mg/m2 in irradiated patients) at three-week intervals. Results: We observed 15 clinical complete responses, 15 partial responses, 9 stable diseases and 6 progressions. The objective response rate was 67% (95% confidence interval: 51%–81%). Ten complete responders underwent subsequent surgery and seven had pathology-defined complete responses (two in irradiated areas). The response rate was 52% in irradiated and 75% in non-irradiated areas. The median survival for non-responders is 6 months, 9+ month for partial responders and 13+ for complete responders. The most relevant side effect was myelotoxicity, with 91% of patients experiencing grade 3–4. One woman had life-threatening toxic effects. Conclusions: This combination is highly effective for salvage treatment in non-irradiated patients. For irradiated women the response rate is higher than that observed with other regimens but further investigation is warranted. The toxicity is relevant but adequate hydration and prolonged infusion of ifosfamide make it acceptable.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008362814642
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  • 7
    Electronic Resource
    Electronic Resource
    Cytomegalovirus colitis after administration of docetaxel–5-fluorouracil–cisplatin chemotherapy for locally advanced hypopharyngeal cancer (1999)
    Springer
    Annals of oncology 10 (1999), S. 1369-1372 
    Details
    ISSN: 1569-8041
    Keywords: cancer ; chemotherapy ; colitis ; cytomegalovirus ; docetaxel ; hypopharynx
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We present the case of a patient with a locally advanced hypopharyngeal carcinoma who developed a severe cytomegalovirus (CMV) colitis after his first chemotherapy course with 5-fluorouracil (5-FU), docetaxel and cisplatin. The most probable cause of his CMV colitis is the impaired immunity during a phase of neutropenia after the chemotherapy. Although there was amelioration of the colitis and clinical status after treatment with ganciclovir, the patient later deteriorated and died due to recurrent bacterial infections. This is the third reported case of CMV colitis treated with ganciclovir in a patient with a solid tumour. It is the first report of CMV colitis after docetaxel containing chemotherapy. Although CMV colitis is most frequently observed in immunosuppressed patients such as those with acquired immune deficiency syndrome (AIDS), transplants and corticosteroid treatment, it has also been reported in less immunosuppressed (elderly, malnourished, ...) and even non-immunosuppressed patients. CMV infection should therefore be included in the differential diagnosis of GI disease in all patients, and when suspected, the clinician should pursue appropriate diagnostic and therapeutic interventions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008357619646
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  • 8
    Electronic Resource
    Electronic Resource
    Management of adenocarcinoma of unknown primary with a 5-fluorouracil–cisplatin chemotherapy regimen (CFTam) (1999)
    Springer
    Annals of oncology 10 (1999), S. 1389-1392 
    Details
    ISSN: 1569-8041
    Keywords: adenocarcinoma ; chemotherapy ; primary ; unknown
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Adenocarcinoma of unknown primary comprises up to 10% of metastatic malignant disease. With few exceptions this diagnosis carries a very poor prognosis of a few months with minimal survival advantage to chemotherapy. However there is the possibility that chemotherapy can improve symptom control and quality of life. Patients and methods: Forty-four patients with adenocarcinoma of unknown primary received CFTam chemotherapy regimen (5-FU 750 mg/m2/day by protracted infusion for five days, cisplatin 60 mg/m2 once and tamoxifen 20 mg daily on a 21-day cycle). Disease response and toxicity were collected and survival compared to patients who were not treated or who received different chemotherapy regimens. Results: Overall response to CFTam was 27% with a median duration of 10 months (range 4–26 months). The chemotherapy was well tolerated with no grade 4 non-haematological toxicity and only three patients (7%) grade 4 neutropaenia with only two (5%) patients developing sepsis. There were no toxic deaths. Performance status was maintained or improved in responders. Conclusions: CFTam is a well tolerated chemotherapy regimen with similar efficacy to other regimens described in the treatment of adenocarcinoma of unknown primary. In the absence of a significant survival advantage there is a need to conduct randomised trials of chemotherapy versus best supportive care to quantify any improvement in quality of life or symptom control.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008309204979
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  • 9
    Electronic Resource
    Electronic Resource
    Local relapse in primary breast cancer patients with unexcised positive surgical margins after lumpectomy, radiotherapy and chemoendocrine therapy (1999)
    Springer
    Annals of oncology 10 (1999), S. 1451-1455 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; chemotherapy ; margins ; radiotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Inadequate surgical excision with residual involvement of resection margins by tumour after breast conservation results in increased local recurrence rates. To reduce this risk positive margins are, therefore, usually excised. Systemic treatment with tamoxifen or chemotherapy reduces local recurrence, along with radiotherapy. However, no studies to date have examined the correlation between chemoendocrine treatment, together with radiotherapy, and local relapse in patients with unexcised involved resection margins, having had breast conservation treatment. Patients and methods: The histopathology reports were reviewed of 184 patients who were treated from June 1991 to August 1995 within our randomised study of neoadjuvant versus adjuvant chemoendocrine therapy with mitozantrone and methotrexate (2M) ± mitomycin-C (3M) and tamoxifen, used concurrently with radiation following conservation surgical treatment. Histological resection margin was considered positive if ductal carcinoma in situ (DCIS) or invasive carcinoma was present microscopically less than 1mm from the excision margin. Results: Although 38% of patients had unexcised microscopically involved margins, local relapse rate as first site of relapse was only 1.9% after a median follow up of 57 months. There was no difference in distant relapse (P = 0.2) and survival (P = 0.5) between the positive and negative margins groups. Conclusions: The presence of positive unexcised margins does not have a significant effect on outcome in patients who are treated with chemoendocrine therapy together with radiotherapy. Further clinical trials are required.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008371318784
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  • 10
    Electronic Resource
    Electronic Resource
    A randomized EPOCH vs. CHOP front-line therapy for aggressive non-Hodgkin's lymphoma patients: Long-term results (1999)
    Springer
    Annals of oncology 10 (1999), S. 1489-1492 
    Details
    ISSN: 1569-8041
    Keywords: aggressive NHL ; chemotherapy ; CHOP ; EPOCH ; phase III randomised trial
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: The value of continuous-infusion chemotherapy (EPOCH) vs. the standard CHOP combination was evaluated in 78 patients with previously untreated aggressive non-Hodgkin's lymphoma in a randomized phase III clinical trial. Patients and methods: The EPOCH regimen given to 38 patients consisted of the drugs etoposide (50 mg/m2), vincristine (0.4 mg/m2), and doxorubicin (10 mg/m2), all given in a continuous infusion on days 1–4. Cyclophosphamide (750 mg/m2) was administered on day 6 as i.v. bolus, while prednisone was given orally 60 mg/m2 on days 1–6. Courses were repeated every three weeks. CHOP was given to 40 patients as routinely prescribed. Results: Forty-eight patients were males and thirty were females. Their ages ranged from 19–75 years (median 45 years). Forty-three (55%) had grade 2 and thirty-five (45%) had grade 3 pathologic subtype. Nine patients (12%) presented with stage I, fourteen (18%) with stage II, forty (51%) with stage Ill, and fifteen (19%) with stage IV disease. The different clinico-pathologic characteristics, including international index categories, were comparable in the two groups. The number of courses given ranged between 3 and 9 (median 6) for both the EPOCH and CHOP regimens. Complete remission (CR) was achieved in 19 (50%), and 27 (67%) of the 38 and 40 patients for both the EPOCH and CHOP combinations, respectively. After a median observation time of 27 months, the four-year overall and failure-free survival rates were 42% and 30% for the EPOCH and 71% and 54% for the CHOP regimen (P = 0.006 and 0.1 for the overall and FFS rates, respectively). Toxicities were comparable and were mostly of grades 1 and 2, except for hair loss, hematologic toxicities, and infectious episodes which were more common in the EPOCH group. In the EPOCH group, overall survival rates were 55% vs. 22% (P 〈 0.04) at four years for the low-risk (2 prognostic factors) and high-risk (〉2 factors) groups, respectively. Conclusions: Thus, it may be concluded that continuous-infusion (EPOCH) chemotherapy did not improve treatment outcome over that of the CHOP regimen for aggressive non-Hodgkin's lymphoma patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008395014398
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  • 11
    Electronic Resource
    Electronic Resource
    Feasibility of tandem autologous stem-cell transplantation (ASCT) in induction failure or very unfavorable (UF) relapse from Hodgkin's disease (HD) (1999)
    Springer
    Annals of oncology 10 (1999), S. 1485-1488 
    Details
    ISSN: 1569-8041
    Keywords: autologous stem-cell transplantation ; chemotherapy ; Hodgkin's disease ; relapses
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Despite high-dose therapy and ASCT some patients with aggressive HD fail to achieve long-term survival. Patients and methods: Forty-three patients with induction failure (n = 19) or very unfavorable (UF) relapse (n = 24) from HD were included in a multicentric study of tandem ASCT. They planned to receive two courses of IVA75 with GCSF and blood stem-cell collection. ASCT1 was conditionned with CBV + mitoxantrone (30 mg/m2) and ASCT2 (cytarabine 6 g/m2, melphalan 140 mg/m2 and total body irradiation at 12 Gy or busulfan 16 (n = 4) than 12 mg/kg). After salvage therapy, response 〉50% was observed in 63% of the patients (six patients were included for refractory relapse). Four patients had no ASCT for disease progression; seven patients had only ASCT1 (disease progression, n = 3) and thirty-two patients (74%) received the two ASCT. Results: Hematologic recovery was normal after ASCT1 but delayed platelet recovery was observed after ASCT2 with busulfan in the conditioning regimen. Two VOD with one fatal occured with busulfan at 16 mg/kg and one hemorragic cystis, no further grade 4 toxicity was observed with the reduced doses of busulfan (12 mg/kg). After ASCT2, 83% of these UF patients were in remission and 20% relapsed within the first year. On an intent-to-treat analysis, 22 of 43 patients are in continuous CR (including 8 patients with induction failure). For the whole population (n = 43) and for patients receiving the two ASCT (n = 32), the two-year survival from the date of progression were respectively at 65% and at 74%. Conclusion: double ASCT is feasible in very UF relapse from HD and may lead to some prolonged remission.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008343823292
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  • 12
    Electronic Resource
    Electronic Resource
    Breast cancer screening by mammography in Norway. Is it cost- effective? (1999)
    Springer
    Annals of oncology 10 (1999), S. 197-203 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; cost-effectiveness ; mammography ; screening
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Mammography screening is a promising method for improving prognosis in breast cancer. Patients and methods: In this economic analysis, data from the Norwegian Mammography Project (NMP), the National Health Administration (NMA) and the Norwegian Medical Association (NMA) were employed in a model for cost-effectiveness analysis. According to the annual report of the NMP for 1996, 60,147 women aged 50–69 years had been invited to a two-yearly mammographic screening programme. 46,329 (77%) had been screened and 337 (0.7%) breast cancers had been revealed. The use of breast conserving surgery (BCS) was in this study estimated raised by 17% due to screening, the breast cancer mortality decreased by 30% and the number of life years saved per prevented breast cancer death was calculated 15 years. Results: The cost per woman screened was calculated £75.4, the cost per cancer detected £10,365 and the cost per life year (LY) saved £8,561. A raised frequency of BCS, diagnosis and adjuvant chemotherapy brought two years forward, follow-up costs and costs/savings due to prevented breast cancer deaths were all included in the analysis. A sensitivity analysis documented mammography screening cost-effective in Norway when four to nine years are gained per prevented breast cancer death. Conclusion: Mammography screening in Norway looks cost- effective. Time has come to encourage national screening programmes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008376608270
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  • 13
    Electronic Resource
    Electronic Resource
    p53-Oriented cancer therapies: Current progress (1999)
    Springer
    Annals of oncology 10 (1999), S. 139-150 
    Details
    ISSN: 1569-8041
    Keywords: apoptosis ; chemotherapy ; clinical trials ; gene therapy ; p53
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Nearly twenty years after the initial discovery of p53, we are now in an ideal position to exploit our vast knowledge of p53 biology in the creation of novel cancer therapies. Disruption of p53 function through mutation, or other means, occurs very frequently in human cancer. Loss of p53 function has been linked with unfavourable prognosis in a large number of tumour types, as indicated by more aggressive tumours, early metastasis and decreased survival rates. Many different avenues of research have converged upon p53 to highlight this protein as being one of the foremost cellular responders to stress, in particular to DNA damage. Huge advances have been made in understanding the complex role p53 plays in the regulation of apoptosis and cell cycle arrest. This review is not meant to be a comprehensive description of p53 biology, but rather serves to highlight current progress in the development of p53- oriented cancer therapies. These may be categorised into three basic strategies: gene replacement therapy using wild-type p53, restoration of p53 function by other means and, finally, targeting of the p53 dysfunction itself. Rapid progress is expected to be made regarding the identification of conventional pharmaceutical agents which either work in a p53-independent manner or act preferentially in p53 defective cells. Gene replacement therapy with wild-type p53 also holds considerable potential for obtaining clinically relevant results quickly. The other forms of cancer therapies based around p53 are much further behind in the developmental process, but may prove to more efficacious in the long run, especially in terms of specificity. As with many other fields, the innovation of successful p53-oriented cancer therapies is only limited by our understanding of p53 biology and the creative use of such knowledge.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008368500557
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  • 14
    Electronic Resource
    Electronic Resource
    Upregulation of basic fibroblast growth factor in breast carcinoma and its relationship to vascular density, oestrogen receptor, epidermal growth factor receptor and survival (1999)
    Springer
    Annals of oncology 10 (1999), S. 707-713 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; fibroblast growth factor ; microvasculature
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Angiogenesis, the process whereby endothelial cells divide and migrate to form new blood capillaries, has been assessed in tumours by measuring microvessel density. High microvessel density is a significant adverse prognostic factor in breast cancer. The angiogenic factor, basic fibroblast growth factor (bFGF), has been associated with tumourigenesis and metastasis in several human cancers. There are few quantitative studies of bFGF expression in normal tissues compared to cancer. Patients and methods: We have measured bFGF levels in 149 human primary breast carcinomas and assessed the findings in relation to microvessel density, oestrogen receptor (ER) and epidermal growth factor receptor (EGFR). Basic FGF levels were measured by ELISA. Western blotting and immunohistochemistry were carreid out to confirm the presence of bFGF. Results: Levels of bFGF were more than 10-fold higher in tumour cytosols compared to reduction mammoplasty tissue and 3-fold compared to non neoplastic cytosols from the same breast as the tumour (P 〈 0.0001). Immunohistochemistry showed bFGF protein was localised exclusively in the stroma whereas no bFGF staining was observed in the epithelial cells. High bFGF levels were significantly related to high ER (P = 0.01). Similarly, high bFGF levels were significantly related to low grade (P = 0.046) and to small tumour size (P = 0.04). No significant relationship was observed between bFGF and microvessel count, EGFR or age. In univariate analysis and in a Cox proportional hazard model bFGF did not reach significance for overall or relapse free survival. Conclusions: Our results show that although bFGF is elevated in breast carcinomas compared to normal breast tissue it is not related to microvessel density and it is not an independent predictor of survival in breast cancer patients. Basic FGF may be one of multiple factors that synergise with other growth factors such as VEGF to enhance angiogenesis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008303614441
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  • 15
    Electronic Resource
    Electronic Resource
    High-dose methotrexate and HELP [Holoxan (ifosfamide), Eldesine (vindesine), platinum] – doxorubicin in non-metastatic osteosarcoma of the extremity: A French multicentre pilot study (1999)
    Springer
    Annals of oncology 10 (1999), S. 1065-1071 
    Details
    ISSN: 1569-8041
    Keywords: chemotherapy ; non-metastatic osteosarcoma ; prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study evaluates histological response, long-term outcome, and toxicity in an intensive chemotherapy program given before surgery. Patients and methods: Sixty-two patients (39 males, 23 females; median age 14) with biopsy, chest computerised-tomography, technetium bone-scan and magnetic resonance imaging, were enrolled. Primary localisations were femur (44%) and tibia (26%). Induction chemotherapy involved seven courses of high-dose methotrexate and two courses of HELP (ifosfamide, eldesine (vindesine), cisplatin (platinum)–doxorubicin. After surgery, patients received six courses of high-dose methotrexate and two courses of HELP–doxorubicin. Results: Pre- and postoperative toxicities were similar. Fifty-nine patients underwent surgery: histological response was good in thirty-eight patients (64%) and poor in twenty-one (36%). Median follow-up is 57 months (range 30–80), with 77% overall survival and 59% progression-free survival. In a multivariate analysis, age under 10 years is the only prognostic factor that significantly correlates with outcome. Conclusions: This regimen appears to increase histological necrosis, but associates with severe toxicity. Results for patients with less necrosis at surgery are encouraging. Future trials should determine the minimum effective doses to reduce toxicity. New drugs should be added.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008395126800
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  • 16
    Electronic Resource
    Electronic Resource
    How Long Should First-line Chemotherapy Continue? (1999)
    Springer
    Annals of oncology 10 (1999), S. 17-20 
    Details
    ISSN: 1569-8041
    Keywords: advanced ovarian cancer ; chemotherapy ; duration ; treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Documentation for the optimal duration of first-line chemotherapy in advanced ovarian cancer is limited. Three randomised trials have compared 5-6 cycles with 8, 10 and 12 cycles respectively. None of the studies showed benefit of chemotherapy beyond 6 cycles. At the moment the standard number of cycles therefore must be 6 cycles. However, these data are based on platinum poly-chemotherapy regimens without taxanes. It may be that the optimal number of cycles is different when using taxanes regimens. It is not possible to tell from the literature if there is a relationship between the number of cycles and response or between the cumulative dose and response. At the moment no trial has shown any benefit of high-dose intensity chemotherapy administered over a short time compared with standard dose chemotherapy administered over a longer period.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008399132535
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  • 17
    Electronic Resource
    Electronic Resource
    Neuroendocrine gastrointestinal tumors – a condensed overview of diagnosis and treatment (1999)
    Springer
    Annals of oncology 10 (1999), S. 3-8 
    Details
    ISSN: 1569-8041
    Keywords: α-interferon ; chemotherapy ; chromogranin A ; octreotide ; receptor scintigraphy ; somatostatin ; surgery
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Neuroendocrine gut and pancreatic tumors are rather rare malignant diseases which has gained increased attraction through the last decennium, possibly through development of new diagnostic and therapeutic methods. Histopathology demonstrating the common neuroendocrine features of these tumors has been the diagnostic corner stone for long, but today it should be supplemented with information about the tumor biology. An excellent biochemical marker which is easy to analyze in serum or plasma is chromogranin A, which is a glycoprotein that is stored and released from neuroendocrine cells. This marker can be used for diagnosis and follow-up of the patients. Somatostatin receptor scintigraphy has been one of the most important diagnostic tools for staging of the disease and also indicating sensitivity to treatment with somatostatin analogues. It is a general agreement that almost every patient should be subjected to this procedure before or during the treatment course. From the therapeutic point of view, surgery is nowadays more extensive aiming at reducing the tumor mass in patients who could not be cured by surgery alone. Other means of tumor reduction is liver dearterialization by embolization with starch spheres. The medical treatment of neuroendocrine tumors has made a real break through with the introduction of somatostatin analogues, particularly octreotide, and today most of the hormonally related symptoms can be controlled by this kind of treatment. Somatostatin analogues have also shown to be inhibitors of tumor growth and the latest development is tumor targeted radioactive treatment with Ytrium or Indium labelled octreotide. Long-acting formulation of somatostatin analogues have come into clinical use and significantly improved quality of life for patients with neuroendocrine tumors. Other means of medical treatment are alpha interferons, which have shown particular effect in patients with midgut carcinoid tumors giving both biochemical and tumor responses. Chemotherapy such as streptozotocin plus 5-fluorouracil (5-FU) or doxorubicin is still considered as first-line treatment in malignant endocrine pancreatic tumors but is combined with concomitant somatostatin analogue treatment. In the future a multimodal treatment will further develop combining different agents and also somatostatin receptor subtype specific analogues will come into clinical use.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1027336026601
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  • 18
    Electronic Resource
    Electronic Resource
    Pancreatic Endocrine Tumours, Immunotherapy and Gene Therapy: Chemotherapy and Interferon Therapy of Endocrine Tumours (1999)
    Springer
    Annals of oncology 10 (1999), S. 185-187 
    Details
    ISSN: 1569-8041
    Keywords: chemotherapy ; endocrine tumours ; immunotherapy ; interferon
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The various pancreatic endocrine tumors (PETs) share histological features with each other and with the carcinoid. The aspects of chemotherapy and/or interferon concern the management of metastatic disease. The value of chemotherapy is difficult to evaluate from the literature because often no distinction is made between the various types of PETs and carcinoids are often also included. Moreover, it has been shown that not each tumor responds equally to chemotherapy, depending on a functioning or non-functioning state of the tumor. In general the response rate to any cytostatic drug, single agents or combinations, is low.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008358819805
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  • 19
    Electronic Resource
    Electronic Resource
    Screening Mammography for Early Detection of Breast Cancer (1999)
    Springer
    Annals of oncology 10 (1999), S. 121-127 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; mammography ; prevention ; screening
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract From numerous studies on breast cancer it can be concluded that no single measure can lessen the burden of this frequent cancer in women in all developed countries. Complex strategies including primary prevention by identification of risk factors and their modification, secondary prevention by earlier detection and tertiary prevention by improving treatment outcome are needed to control the disease. Besides age, the established breast cancer risk factors include certain benign breast diseases, family history, ionising radiation, some reproductive factors and obesity. Primary prevention includes general recommendation for healthy lifestyle, e.g., avoidance of obesity, proper diet, physical activity and moderate alcohol consumption. Randomised controlled trials conducted in the USA, Canada, Scotland and Sweden have shown that regular mammography, alone or in combination with clinical examination, is effective in reducing mortality for about 30% in women over the age of 50, and much less in younger population. However, mammography screening has several drawbacks, the major being its tendency towards false positive and false negative results with all their potential psychosocial consequences. High quality assurance and control, as well as effective and readily available treatment, all of which demand high investments, are indispensable for good results. Even in the absence of organised screening, the availability of effective treatment may contribute to reduction in breast cancer mortality.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008310503380
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  • 20
    Electronic Resource
    Electronic Resource
    Treatment of Small Cell Lung Cancer Patients (1999)
    Springer
    Annals of oncology 10 (1999), S. 83-91 
    Details
    ISSN: 1569-8041
    Keywords: chemotherapy ; new drugs ; radiotherapy ; small cell lung cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Small cell lung cancers, comprising approximately 20% of lung cancers, are rapidly growing and disseminating carcinomas which are initially chemosensitive but acquire drug resistance during the course of disease. Thus, outcome is poor with median survival of 10-16 months for patients with limited and 7-11 months for patients with extensive disease. Polychemotherapy with established drugs (platins, etoposide, anthracyclines, cyclophosphamide, ifosfamide and Vinca alkaloids) plays the major role in the treatment of this disease and results in overall response rates between 80%-95% for limited disease and 60%-80% for extensive disease. Dose-intensified chemotherapy and high-dose chemotherapy with peripheral blood progenitor cell support were tested in several trials but their exact impact on outcome remains to be determined. New drugs including the taxanes (paclitaxel, docetaxel), the topoisomerase I inhibitors (topotecan, irinotecan), vinorelbine and gemcitabine are currently evaluated in clinical trials. In limited disease, thoracic radiotherapy improves survival and prophylactic cranial irradiation should be administered to those with a reasonable chance of cure.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008333713858
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  • 21
    Electronic Resource
    Electronic Resource
    Chemotherapy of Chagas’ disease: the how and the why (1999)
    Springer
    Journal of molecular medicine 77 (1999), S. 332-338 
    Details
    ISSN: 1432-1440
    Keywords: Key words Chagas" disease ; Trypanosoma cruzi ; chemotherapy ; sterol biosynthesis inhibitors ; nitrofurans ; nitroimidazoles ; autoimmunity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Current developments in experimental chemotherapy of Chagas’ disease are reviewed, in particular the demonstration that fourth-generation azole derivatives (inhibitors of sterol C14α demethylase), with particular selectivity against Trypanosoma cruzi and special pharmacokinetic properties, are capable of inducing radical parasitological cures in murine models of both acute and chronic disease. These are the first reports of parasitological cure of this disease in its chronic phase. We also discuss the relevance of etiological treatment in the clinical outcome of patients with chronic Chagas’ disease. Although previous studies have suggested an important autoimmune component in the pathogenesis of this disease, recent results obtained using highly sensitive polymerase chain reaction based detection methods and detailed immunological characterization of the inflammatory process associated with chagasic cardiomyopathy indicate a positive correlation between tissue parasitism and the severity of cardiac pathological findings. Effective antiparasitic treatment can lead to regression of the inflammatory heart lesions and fibrosis in experimental animals and to stop the progression of the disease in humans. Taken together, these findings support the notion that the presence of the parasite is a necessary and sufficient condition for chagasic cardiomyopathy and confirm the importance of specific etiological treatment in the management of chronic chagasic patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001090050359
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  • 22
    Electronic Resource
    Electronic Resource
    Essential drugs for cancer therapy: A World Health Organization consultation (1999)
    Springer
    Annals of oncology 10 (1999), S. 385-390 
    Details
    ISSN: 1569-8041
    Keywords: chemotherapy ; drugs ; generics ; prioritization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The WHO has previously produced recommendations on the essential drugs required for cancer therapy. Over the last five years several new anti cancer drugs have been aggressively marketed. Most of these are costly and produce only limited benefits. We have divided currently available anti-cancer drugs into three priority groups. Curable cancers and those cancers where the cost-benefit ratio clearly favours drug treatment can be managed appropriately with regimens based on only 17 drugs. All of these are available, at relatively low cost, as generic preparations. The wide availability of these drugs should be the first priority. The second group of drugs may have some advantages in certain clinical situations. Based on current evidence, drugs in the third group are judged as currently not essential for the effective delivery of cancer care. Adequate supportive care programmes with the widespread availability of effective drugs for pain control are of considerably greater importance. The adoption of these priorities will help to optimise the effectiveness and efficiency of chemotherapy and ensure equitable access to essential drugs especially in low resource environments. Clearly this paper represents the views of its contributors. The WHO welcomes feedback from all oncologists so that the advice it gives to governments in prioritising the procurement of anti cancer drugs can be as comprehensive as possible.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008367822016
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  • 23
    Electronic Resource
    Electronic Resource
    Cytomegalovirus pneumonia in a patient with breast cancer on chemotherapy: Case report and review of the literature (1999)
    Springer
    Annals of oncology 10 (1999), S. 461-465 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; cytomegalovirus pneumonia ; dexamethasone ; ganciclovir ; standard dose chemotherapy regimen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Cytomegalovirus (CMV) pneumonia in the setting of non-transplantation patients is a rarity. We present a case of CMV pneumonitis in a woman with stage IV breast cancer, with brain metastases, receiving both chemotherapy and systemic corticosteroids. A review of the literature reveals this as a unique case. Potential viral etiologies should therefore be considered in cancer patients with pneumonia receiving non-transplantation chemotherapy-regimens, particularly if steroids are a component of their therapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008360927507
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  • 24
    Electronic Resource
    Electronic Resource
    Paclitaxel by 24-hour infusion with doxorubicin by 48-hour infusion as initial therapy for metastatic breast cancer: Phase I results (1999)
    Springer
    Annals of oncology 10 (1999), S. 403-411 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; doxorubicin ; paclitaxel-anthracycline combination ; schedule
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: We and others have demonstrated the antineoplastic efficacy of paclitaxel as a single agent in metastatic breast cancer. We performed this phase I trial to evaluate the combination of paclitaxel with doxorubicin. Patients and methods: Eligible patients had measurable or evaluable metastatic breast cancer for which this was the initial cytotoxic treatment. They may have received adjuvant chemotherapy with other drugs. The study had four parts. In part 1, the patients received paclitaxel by 24-hour infusion followed by doxorubicin by 48-hour infusion. The paclitaxel dose was to be escalated from a starting dose of 125 mg/m2, and the doxorubicin dose was to remain constant at 60 mg/m2 with treatment repeated every three weeks. The results of part 1 prompted part 2 which was a study of the reverse sequence. Part 3 was a formal study of pharmacology and has been reported (J Clin Oncol 14: 2713–21, 1996). In part 4, patients received doxorubicin 50 mg/m2 by bolus followed by paclitaxel 150 mg/m2 by 24-hour infusion for courses 1 and 2. In all subsequent courses doxorubicin was administered by 48-hour infusion. All patients in all four parts of the study had baseline cardiac scans. All patients received standard premedication for paclitaxel. Results: Forty-eight patients were treated in all four parts of the study. In part 1 (10 patients), the maximum tolerated dose (MTD) was paclitaxel 125 mg/m2/24 hours followed by doxorubicin 48 mg/m2/48 hours as defined by dose-limiting mucositis and neutropenic fever which occurred at the starting dose. For part 2 (21 patients), the MTD was doxorubicin 60 mg/m2/48 hours followed by paclitaxel 160 mg/m2/24 hours. In part 4 (seven patients), the MTD was doxorubicin 50 mg/m2/bolus followed by paclitaxel 135 mg/m2/24 hours. In parts 2 and 4, the dose-limiting toxic effect was neutropenia. Of the entire cohort of 48 patients, seven (15%) had a complete response (one persists at five years without intervening therapy), 26 (54%) had a partial response for an objective response rate of 69% (95% confidence interval (95% CI): 54%–81%). The median follow-up of all living patients is 38+ months (range 20+ to 62+); the median response duration is seven months (range 2–33.7+); the median overall survival is 20.5 months (range 5–54+). The median time to progression is 9.6 months (range 1–33.7+ months). Two patients developed congestive heart failure, one at 24 months after her final dose of doxorubicin which amounted to a cumulative lifetime total doxorubicin dose of 870 mg/m2, one after a total of 660 mg/m2. In both, cardiac symptoms were controlled with medications. Conclusions: The combination of paclitaxel/24 hours with doxorubicin/48 hours is an effective antineoplastic treatment for metastatic breast cancer. However, the incidence of complete response, the median overall survival, and time to progression were not greater than for standard doxorubicin-based combinations. Additionally, a sequence-dependent interaction between paclitaxel and doxorubicin, given in the schedule described here, was defined. Other strategies and schedules should be evaluated to maximize the antineoplastic efficacy of these two potent agents.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008360406322
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  • 25
    Electronic Resource
    Electronic Resource
    Standard- and high-dose etoposide, ifosfamide, carboplatin, and epirubicin in 100 patients with small-cell lung cancer: A mature follow-up report (1999)
    Springer
    Annals of oncology 10 (1999), S. 561-567 
    Details
    ISSN: 1569-8041
    Keywords: chemotherapy ; hematopoietic growth-factor support ; high-dose chemotherapy ; peripheral blood stem-cell transplantation ; small-cell lung cancer ; treatment toxicity and mortality
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: We conducted a phase I–II trial to assess the feasibility and activity of a combination chemotherapy regimen with etoposide, ifosfamide, cisplatin or carboplatin, and epirubicin in limited-disease (LD, stages I–IIIB) and extensive-stage (ED, stage IV) small-cell lung cancer (SCLC). Patients and methods: Standard-dose chemotherapy (SDC) consisting of etoposide (500 mg/m2), ifosfamide (4000 mg/m2), cisplatin (50 mg/m2) and epirubicin (50 mg/m2) (VIP-E), followed by granulocyte colony-stimulating factor (G-CSF), was given to 100 patients with SCLC. Thirty patients with qualifying responses to VIP-E proceeded to high-dose chemotherapy (HDC) with autologous peripheral blood stem-cell transplantation (PBSCT) after etoposide (1,500 mg/m2), ifosfamide (12,000 mg/m2), carboplatin (750 mg/m2) and epirubicin (150 mg/m2) (VIC-E) conditioning. Results of standard-dose VIP-E: Ninety-seven patients were evaluable for response. The objective response rate was 81% in LD SCLC (33% CR, 48% PR; excluding patients in surgical CR) and 77% in ED SCLC (18% CR, 58% PR). The treatment-related mortality (TRM) of SDC was 2%. Two additional patients in CR from their SCLC developed secondary non-small-cell lung cancers (NSCLC), and both were cured by surgery. The median survival was 19 months in LD SCLC and 6 months in ED SCLC. The five-year survivals were 36% in LD and 0% in ED SCLC. Results of high-dose VIC-E: HDC was feasible in 16% of ED-, and 58% of LD-patients. All HDC patients (n = 30) improved or maintained prior responses. Four patients died of early treatment-related complications (TRM 13%). Two additional patients in CR from their SCLC developed secondary malignancies (esophageal cancer, secondary chronic myelogenous leukemia). The median survivals were 26 months in LD SCLC, and 8 months in ED SCLC. The five-year survival was 50% in LD and 0% in ED SCLC. Conclusions: Despite high response rates, survival after VIP-E SDC and VIC-E HDC in patients with ED SCLC is not superior to that achieved with less toxic traditional regimens. The high five-year survival rates achieved with these protocols in LD SCLC probably reflect both patient selection (high proportion of patients with prior surgical resection) and the high activity of our chemotherapy regimen in combination with radiotherapy. A study comparing protocols using simultaneous radiation therapy and chemotherapy, and other dose-escalated forms of SDC with HDC is needed to further define the role of this treatment modality in SCLC. Given the high rate of secondary malignancies observed in patients in CR 〉2 years in our study, close follow-up and early treatment of these neoplasms may contribute to maintaining overall survival in patients with SCLC.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1026453922931
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  • 26
    Electronic Resource
    Electronic Resource
    Front-line treatment of metastatic breast cancer with docetaxel and epirubicin: A multicenter dose-escalation study (1999)
    Springer
    Annals of oncology 10 (1999), S. 547-552 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; docetaxel ; epirubicin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: To determine the maximum tolerable dose (MTD) and the dose-limiting toxicity (DLT) of docetaxel (D) in combination with epirubicin (Epi) in patients with advanced breast cancer. Patients and methods: Forty-seven chemotherapy-naïve metastatic breast cancer patients aged 〈75 years with PS (WHO) 0–2 and adequate bone marrow, renal, liver and cardiac function, were enrolled in the study. Epi was given as a five-min bolus i.v. infusion on day 1 (d1) in escalated doses with increments of 10 mg/m2; D was given in a one-hour infusion after appropriate premedication on either day 1 or on day 2 in escalated doses with increments of 10 mg/m2. The patients' median age was 60 years, 42 (89%) had a PS (WHO) 0–1, 16 (34%) were premenopausal and 25 (53%) had visceral disease. Results: When the two drugs were given on the same day, the MTD1 was reached at the doses of Epi 60 mg/m2 and D 80 mg/m2; administration of G-CSF could not result in a dose intensification. When the drugs were given on two consecutive days, the MTD2 was reached at the doses of Epi 80 mg/m2 (d1) and D 90 mg/m2 (d2). The dose-limiting events were febrile neutropenia and grade 4 neutropenia, which developed in 30 (64%) patients during the study; among 227 delivered cycles grade 3–4 neutropenia occurred in 64 (28%) cycles but only 22 (10%) of them were complicated by fever. There were no septic deaths. Grade 1–2 neurosensory toxicity occurred in nine (19%) patients, mild edema in eight (17%) and allergic reactions in five (11%). Four (9%) patients presented a greater than 10% decrease of LVEF and treatment discontinuation was required in two of them; none of the patients developed congestive heart failure. Nevertheless, one patient suddenly died 10 days after treatment initiation of myocardial ischemia, and this death is considered treatment-related. Five (14.7%) complete and thirteen (38.2%) partial responses (ORR: 53.9%; 95% confidence interval: 36.1%–69.7%) were observed in 34 evaluable patients. Ten (29.4%) and six (17.6%) patients had stable and progressive disease, respectively. The median duration of response and time to tumor progression were five and seven months, respectively. The median survival has not yet been reached. Conclusions: The combination of epirubicin and docetaxel is a feasible and well tolerated regimen, but the MTD depends on the administration schedule of the drugs.
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    URL: http://dx.doi.org/10.1023/A:1026441804889
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  • 27
    Electronic Resource
    Electronic Resource
    Depression in breast cancer patients: The need for treatment (1999)
    Springer
    Annals of oncology 10 (1999), S. 627-636 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; depression ; diagnosis ; treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008328005050
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  • 28
    Electronic Resource
    Electronic Resource
    Primary chemotherapy in operable breast cancer with favorable prognostic factors: A pilot study evaluating the efficacy of a regimen with a low subjective toxic burden containing vinorelbine, 5-fluorouracil and folinic acid (FLN) (1999)
    Springer
    Annals of oncology 10 (1999), S. 993-996 
    Details
    ISSN: 1569-8041
    Keywords: 5-fluorouracil ; breast cancer ; neoadjuvant ; primary chemotherapy ; vinorelbine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Biological considerations support the use of primary chemotherapy in operable breast cancer; and despite wide variations of used regimens, clinical studies consistently show a significant tumor response allowing breast conservation in many patients otherwise canditates for mastectomy. We investigated the efficacy and the acceptance of a combination chemotherapy with vinorelbine, 5-fluorouracil and high-dose folinic acid in operable breast cancer with favorable prognostic factors and tested the relationship of hormone receptor status, Ki67, p53, c-erbB2 and bcl-2 with treatment response. Patients and methods: Thirty-nine patients (median age 51 years, range 36–71 years), eight with T1, twenty-eight with T2 and two with T3 lesions, were treated with 5-fluorouracil (350 mg/m2, i.v. on day 1 to 3) preceded by folinic acid (100 mg/m2 i.v. on day 1 to 3) and vinorelbine, given on days 1 and 3 at the dose of 20 mg/m2 (FLN regimen). Therapy was administered on an outpatient basis every three weeks. Non responders had surgery after three courses, while complete or partial responders underwent surgery after six courses. All but one were evaluable for response and toxicity. Results: Objective responses were observed in 23 of the 38 evaluable patients (61%; 95% CI: 46%–76%): three complete responses (8%) and 20 partial responses (53%). Fifteen patients (39%) had stable disease, of whom nine (23%) had minor response. None of the patients had disease progression during treatment. Objective responses were significantly associated with no expression of estrogen and/or progesteron receptors and 〉50% decrease in Ki67 after induction chemotherapy. Tolerance was excellent and none of the patients experienced grade 2 alopecia. Conclusions: The ‘moderate’ efficacy of this regimen might be partially due to the selection of patients with high expression of steroid hormone receptors and low proliferation rate, which have an unfavorable impact on response to this chemotherapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008389106575
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  • 29
    Electronic Resource
    Electronic Resource
    Chemoradiation for Pancreatic and Biliary Cancer: Current Status of RTOG Studies (1999)
    Springer
    Annals of oncology 10 (1999), S. 231-233 
    Details
    ISSN: 1569-8041
    Keywords: chemoradiation ; chemotherapy ; 5FU ; gemcitabine ; radiotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Chemoradiation for gastrointestinal cancers is actively under study in the Radiation Therapy Oncology Group (RTOG) and consists of external irradiation combined with simultaneously administered chemotherapy given to provide radiation sensitization and to attack micro metastatic disease. Two national protocols for the treatment of patients with pancreatic and biliary cancers are now active. RTOG 97-04 is a phase III post-operative combined modality program for patients with resected pancreatic cancer. All patients receive protracted infusional 5-fluorouracil (5-FU) combined with 50.4 Gy given in 28 fractions. Prior to and after chemoradiation all patients are randomized to receive multiple cycles of either infusional 5-FU or Gemcitabine to determine the effect on survival. In the other study (RTOG 98-12) patients with unresectable pancreatic cancer are given 50.4 Gy combined with weekly Paclitaxel (50 mg/m2) to examine the efficacy of this active combination in a phase II trial in a multi-institutional setting. Both of these trials have recently been opened to accrual. A third RTOG study for patients with biliary cancer will examine the efficacy of giving pre-operative chronomodulated infusional 5-FU chemoradiation. The background and the rationale for these studies is based on the long history of 5-FU radiation sensitization in the treatment of cancers of these anatomic sites and will be summarized. A brief review of recently published trials using chemoradiation in conjunction with new irradiation treatment techniques with "3D" conformal therapy for these diseases will be discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008347911144
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  • 30
    Electronic Resource
    Electronic Resource
    The combination of etoposide and cisplatin in non-small-cell lung cancer (NSCLC) (1999)
    Springer
    Annals of oncology 10 (1999), S. 13-17 
    Details
    ISSN: 1569-8041
    Keywords: advanced disease ; chemotherapy ; cisplatin ; etoposide ; non-small-cell lung cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The role of chemotherapy in the treatment of advanced non-small-cell lung cancer (NSCLC) has been a subject of debate for many years. Only recently, cisplatin-based combination chemotherapy has been demonstrated to yield a small but definite survival benefit and to improve symptoms, performance status and quality of life in a substantial proportion of advanced NSCLC patients. The cisplatin–etoposide (PE) regimen was developed in the early 1980s and has been one of the standard chemotherapy programs most extensively used in the clinical practice until a few years ago. More recently, several randomized trials have compared the efficacy of new cisplatin-containing combination chemotherapies including Paclitaxel or Gemcitabine with that of PE or PE-like regimens. Preliminary results are encouraging, indicating a small benefit in favor of the last generation of regimens which might therefore replace PE as 'gold standards' in the treatment of advanced NSCLC. However, the costs of these last generation regimens is higher and the entity of the benefit small. Therefore, PE chemotherapy can still be an option in selected situations.
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    URL: http://dx.doi.org/10.1023/A:1008383600448
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  • 31
    Electronic Resource
    Electronic Resource
    Chemotherapy of non-small-cell lung cancer: Role of erythropoietin in the management of anemia (1999)
    Springer
    Annals of oncology 10 (1999), S. 89-92 
    Details
    ISSN: 1569-8041
    Keywords: anemia ; chemotherapy ; erythropoietin ; lung cancer ; review ; toxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Main mechanisms involved in the development of chemotherapy-induced anemia are the direct bone marrow damage and the renal impairment with a secondary deficient production of erythropoietin. The first mechanism is induced by almost all cytotoxic drugs whilst the second one has been demonstrated with cisplatin treatment. NSCLC patients are generally treated with platinum-based chemotherapy and then both mechanisms are involved in the development of anemia which can be, as a consequence, more frequent and more severe compared to other cancer patients. Chemotherapy regimens such as MVP (mitomycin, vindesine, platin), cisplatin–etoposide and cisplatin–teniposide induce grade ≥2 anemia in 64%, 46% and 83% of patients, respectively, with grade 3–4 anemia occurring in 29%, 15% and 24% of patients. New chemotherapy regimens are also associated with a high incidence of anemia. Carboplatin–paclitaxel induces grade 3–4 anemia in 34% of patients and 30% of patients need blood transfusions. Similarly, 33% of patients treated with cisplatin-gemcitabine require blood transfusions. Erythropoietin is able to correct anemia in nearly 60%–80% of patients receiving platinum-based chemotherapy and in nearly 40% of patients treated with regimens without platinum compounds, leading to a reduction in blood transfusion requirement. Moreover, erythropoietin is able to prevent anemia development in cancer patients. Due to the high incidence of anemia, erythropoietin may represent an important tool in the supportive care of NSCLC patients. Erythropoietin use is mainly limited by the economic cost and then efforts should be made to identify the subset of patients in whom this supportive therapy is cost-effective. Patient and disease characteristics, factors predicting the probability to be transfused as well as factors predicting the response to erythropoietin can be useful in selecting patients likely to benefit from erythropoietin therapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008333111351
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  • 32
    Electronic Resource
    Electronic Resource
    Adjuvant Therapy of Breast Cancer: Update (1999)
    Springer
    Annals of oncology 10 (1999), S. 129-137 
    Details
    ISSN: 1569-8041
    Keywords: adjuvant treatment ; breast cancer ; systemic therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The theoretical prediction that breast cancer is a systemic disease, and that patients may benefit from addition of systemic therapy to local treatment, has now been confirmed by three decades of clinical investigations. A long-term follow up of individual trials and the International Overview based on meta-analyses clearly showed the potential of both hormonal therapies and chemotherapy to prolong disease-free and overall survival in nearly all groups of patients. The benefits have been demonstrated for both premenopausal and postmenopausal patients, with both node-negative and node-positive disease. However, there is still considerable uncertainty regarding the most appropriate treatment for each individual patient. In the present review, the results of meta-analysis are highlighted in the context of the new trials supporting the value of chemoendocrine therapy and anthracycline-based therapy. The results of prospective randomised trials evaluating the role of dose intensification, drug sequencing and dose density are discussed. Also presented are new treatment strategies, such as preoperative chemotherapy and high-dose chemotherapy with stem cell support, the value of which remains to be confirmed. Future possibilities opened by inclusion of biologics into adjuvant therapy are discussed.
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    URL: http://dx.doi.org/10.1023/A:1008362521127
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  • 33
    Electronic Resource
    Electronic Resource
    New Developments in Chemotherapy of Advanced Breast Cancer (1999)
    Springer
    Annals of oncology 10 (1999), S. 139-146 
    Details
    ISSN: 1569-8041
    Keywords: anthracycline ; breast cancer ; chemotherapy ; HER-2 antibody ; N,N-diethyl-2[4-(phenylmethyl)-phenoxy] ethanamine.HCl (DPPE, BMS-217380-01) ; paclitaxel
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Anthracyclines and taxanes are the two most active classes of chemotherapy for the treatment of advanced breast cancer. Recent studies have investigated combination therapy including doxorubicin (Dox) and paclitaxel. The efficacy of this combination has been established in a phase III study conducted by ECOG, comparing Dox/paclitaxel versus Dox versus paclitaxel. The combination is superior to Dox or paclitaxel with respect to response rate and time to disease progression, indicating that the combination provides a new standard for the first line treatment of metastatic breast cancer [1]. Phase II studies using higher doses of Dox and using shorter infusions of paclitaxel have suggested the combination can be further optimised; Gianni reported a 94% objective response rate using Dox 60 mg/m2 followed by paclitaxel 175 mg/m2 given over three hours [2]. The more active regimens are associated with enhanced cardiotoxicity; this toxicity can be avoided, however, by limiting the exposure to doxorubicin. The newer regimens have now been moved into phase III studies. Future progress for this disease will depend on the introduction of new agents. Two novel drugs are currently being investigated in randomised phase III trials as potentiators of Dox and/or paclitaxel. One is a monoclonal antibody from Genentech (Herceptin, trastuzumab) directed at the HER-2/neu oncogene, which is overexpressed in 〉25% of breast cancers [3]. Recent results indicate that Herceptin in combination with paclitaxel (or with a Dox plus cyclophosphamide regimen) induces a higher response rate (RR) and prolongs the time to disease progression when compared to chemotherapy alone. The second agent N,N-diethyl-2[4-(phenylmethyl)-phenoxyl] ethanamine.HCl (DPPE, BMS-217380-01), when combined with Dox, was associated with a higher RR than previously observed with Dox alone [4]. A randomised trial of Dox versus Dox plus DPPE is ongoing. The possible mechanisms underlying chemo-potentiation by these agents are discussed. As new anthracycline/taxane combinations establish themselves in earlier stages of the disease, the need for effective, non-cross resistant salvage regimens will emerge.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008318725670
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  • 34
    Electronic Resource
    Electronic Resource
    Oral Mucosal Permeability and Stability of Transforming Growth Factor Beta-3 In Vitro (1999)
    Springer
    Pharmaceutical research 16 (1999), S. 1557-1563 
    Details
    ISSN: 1573-904X
    Keywords: transforming growth factor ; permeability ; chemotherapy ; oral mucosa ; mucositis and pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To investigate the permeability and localization of topically applied 125I-TGF-β3 in porcine floor-of-mouth mucosa as a function of concentration and exposure. Methods. The 125I-TGF-β3 diluted in three different vehicles was applied to the tissue samples mounted in perfusion cells maintained at 37°C. Flux and Kp values were calculated from the perfusate collected over a 24 hour period. The quantity of 125I-TGF-β3 present in the tissue was determined by horizontal sectioning and subsequent counting. The stability of 125I-TGF-β3 in saliva and in the tissue was analyzed by SDS polyacrylamide gradient gel electrophoresis. Results. 125I-TGF-β3 was relatively stable in saliva and in the epithelium; approximately 50% of the total counts in the deeper epithelium were resident in the 25kDa TGF-β3 homodimer. A steady-state flux was reached ∼6 hours post application and Kp value was 4.0 ± 0.6 × 10-6 (mean ± sem). Penetration of 125I-TGF-β3 to the basal cell layer was concentration dependent but reached nanomolar concentrations even after extensive surface rinsing, representing over one-thousand fold the IC50 for epithelial cell cycle arrest. Conclusions. The data suggest that topical application of TGF-β3 to the oral mucosa in an appropriate vehicle can provide effective therapeutic delivery to the tissue.
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    URL: http://dx.doi.org/10.1023/A:1015052520467
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  • 35
    Electronic Resource
    Electronic Resource
    A phase II study of cisplatin, ifosfamide and doxorubicin in operable primary, axial skeletal and metastatic osteosarcoma (1999)
    Springer
    Annals of oncology 10 (1999), S. 1211-1218 
    Details
    ISSN: 1569-8041
    Keywords: chemotherapy ; osteosarcoma ; relative dose intensity ; survival ; tumour response
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Despite advances in the treatment of primary limb osteosarcoma, the outcome of patients with primary metastatic and axial skeletal disease remains poor. The European Osteosarcoma Intergroup have assessed a combination chemotherapy regimen consisting of ifosfamide (IFOS) 3 g/m2/d1–2, doxorubicin (DOX) 25 mg/m2/d1–3 i.v. bolus and cisplatin (CDDP) 100 mg/m2/d1. Patients and methods: One hundred nine previously untreated patients with primary osteosarcoma were registered. Eligibility was confirmed in 103. At presentation, 45 eligible patients had metastatic disease, 15 axial skeletal primary tumours and 43 non-metastatic limb tumours. Results: The major toxicities were myelosuppression (90%, grade 3 or 4) and nausea and vomiting (74%, grade 3 or 4). Overall mean relative dose intensity (RDI) was 80% (88% CDDP, 75% IFOS, 81% DOX). Clinical response as measured by reduction in tumour volume occurred in 36% (95% confidence interval (95% CI): 27%–47%) of primary tumours. Response of pulmonary metastases to chemotherapy was seen in 33% (95% CI: 19%–49%). Good histological response (≥90% necrosis of the tumour) occurred in 33% (95% CI: 22%–45%) of resected tumours. Five-year survival was 62% in limb-non-metastatic, 41% in axial skeletal and 16% in limb metastatic patients. Conclusions: This regimen is active in osteosarcoma but does not appear to be more active than the two-drug CDDP–DOX regimen currently recommended by EOI.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008361612767
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  • 36
    Electronic Resource
    Electronic Resource
    Cardiac effects of high-dose epirubicin and cyclophosphamide in women with poor prognosis breast cancer (1999)
    Springer
    Annals of oncology 10 (1999), S. 53-58 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; cardiotoxicity ; cyclophosphamide ; epirubicin ; high dose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: To prospectively evaluate the long term cardiac effects of high-dose epirubicin and cyclophosphamide given to women with early stage, poor prognosis breast cancer. Patients and methods: Women with stage 2 breast cancer and 10+ nodes or 4+ nodes and estrogen receptor negative tumor, or stage 3 breast cancer received three cycles of epirubicin 200 mg/m2 and cyclophosphamide 4 gm/m2 with peripheral blood progenitor cell and filgrastim support. Treatment was given every 28 days (n = 79) or 21 days (n = 20). Fifty patients received radiotherapy to the chest wall or breast, 25 of to the left side. Patients were assessed clinically regularly during chemotherapy and at least three times yearly after completion of treatment. Cardiac left ventricular ejection fraction (LVEF) was assessed by radionuclide scan before therapy, after each cycle of chemotherapy, three months and six months after completion of chemotherapy, and yearly thereafter until relapse. Results: Ninety-nine women were treated, and 92 completed all three cycles of chemotherapy. The median age was 43 years (range 24 to 60 years). All patients were included in this analysis. The median relapse-free survival was 39 months (11 to 68 months). There was a significant fall in LVEF during chemotherapy. In general, there was no further deterioration in cardiac function from the third month after cessation of treatment, however there was substantial variation between individuals. 35 patients had at least one LVEF measure less than normal (〈50%), but the LVEF returned to normal in 20 of these with further follow-up. Cardiac dysfunction was not increased in women who received radiotherapy and was not different between cohorts given chemotherapy every three or every four weeks. One patient died of acute myocardial necrosis following the third cycle of chemotherapy. Two patients developed clinical evidence of cardiac failure, and another had radiological signs but was asymptomatic. One woman died of progressive cardiac failure, one recovered clinically but also developed recurrent breast cancer, while the third recovered after commencement of medical therapy. Conclusions: During follow-up after high-dose epirubicin and cyclophosphamide as delivered in this study, the LVEF fell to below normal in approximately one third of patients. However, in over half of these patients the LVEF subsequently recovered to the normal range, and the incidence of clinically evident chronic cardiac failure was low. Further follow-up is required to assess the long- term safety. A randomized comparison with standard-dose anthracycline-based chemotherapy is needed to determine whether this regimen is associated with an increased risk of clinical cardiac toxicity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008390203340
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  • 37
    Electronic Resource
    Electronic Resource
    Cowden disease and Lhermitte Duclos disease, markers of breast carcinoma: Report of two patients (1999)
    Springer
    Annals of oncology 10 (1999), S. 1241-1243 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; Cowden disease ; Lhermitte Duclos
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008317923860
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  • 38
    Electronic Resource
    Electronic Resource
    A randomized, open, parallel-group trial to compare the endocrine effects of oral anastrozole (Arimidex®) with intramuscular formestane in postmenopausal women with advanced breast cancer (1999)
    Springer
    Annals of oncology 10 (1999), S. 1219-1225 
    Details
    ISSN: 1569-8041
    Keywords: anastrozole ; Arimidex® ; aromatase inhibitor ; breast cancer ; formestane ; oestradiol ; tolerability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: This study provides a direct randomized comparison of a new-generation, non-steroidal aromatase inhibitor, anastrozole (Arimidex®), with a steroidal aromatase inhibitor (formestane) with respect to oestrogen (oestradiol, oestrone, and oestrone sulphate) suppression and tolerability. Patients and methods: Sixty postmenopausal women with advanced breast cancer were randomized to receive either anastrozole 1 mg once daily orally (n = 29), or formestane 250 mg once every two weeks by intramuscular injection (n = 31). Treatment was continued until progression of disease or withdrawal from the study. The primary endpoints of this study were oestradiol suppression and tolerability. The secondary endpoints included oestrone and oestrone sulphate suppression. All laboratory analyses were conducted ‘blind’ of the randomized drug treatment. Results: Anastrozole produced a greater and more consistent suppression of oestradiol levels compared with formestane. Based on two- and four-week measurements, the mean fall from baseline (pre-dose) in oestradiol level was 79% and 58% in the anastrozole and formestane groups, respectively (P = 0.0001). After four weeks of treatment, oestrone and oestrone sulphate levels were also suppressed to a greater extent by anastrozole compared with formestane (oestrone: 85% versus67%, respectively, P = 0.0043; oestrone sulphate: 92% versus 67%, respectively, P = 0.0007). No statistical differences were seen between the two drugs in the incidence of adverse events. Conclusions: Anastrozole provides a more consistent and significantly more effective suppression of oestradiol compared with formestane. Similar results were observed for oestrone and oestrone sulphate. The clinical significance of these differences in total oestrogen suppression remains to be established.
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    URL: http://dx.doi.org/10.1023/A:1008308609325
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  • 39
    Electronic Resource
    Electronic Resource
    Survival impact of chemotherapy in patients with colorectal metastases confined to the liver: A re-analysis of 1458 non-operable patients randomised in 22 trials and 4 meta-analyses (1999)
    Springer
    Annals of oncology 10 (1999), S. 1317-1320 
    Details
    ISSN: 1569-8041
    Keywords: advanced colorectal cancer ; chemotherapy ; meta-analysis ; non-operable metastases confined to the liver
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Metastases confined to the liver is a frequent situation in patients with advanced colorectal cancer. For non-operable patients, 5-FU-based chemotherapy is often proposed but the importance of the choice of first line 5-FU regimen remains debatable. Design: In four previously performed meta-analyses, our group had compared bolus intravenous fluoropyrimidines (bolus FU group) with experimental fluoropyrimidines (experimental FU group), consisting of 5-FU plus leucovorin, 5-FU plus methotrexate, continuous infusion 5-FU, or hepatic-artery infusion FUDR. We re-analysed this data set to focus on 1458 patients with non-operable colorectal metastases confined to the liver, randomised in 22 trials. All analyses were stratified by trial and used individual patient data. Results: Median survival times were 11.3 months in the bolus FU group (95% CI: 10.5–12.0 months) compared to 12.7 months in the experimental FU group (95% CI: 12.0–13.1 months). This difference, although clinically small, was statistically significant, with an overall survival hazard ratio of 0.88 (95% CI: 0.79–0.99, P = 0.037). In a multivariate analysis, performance status was the only significant predictor of survival (P 〈 10−4), whereas the statistical significance of allocated treatment was borderline (P = 0.058). Conclusions: The outcome of patient with non-operable colorectal metastases confined to the liver is poor, and mainly driven by their initial performance status. Experimental chemotherapy schedules yield a small improvement in their overall survival, indicating the importance of the choice of first-line chemotherapy.
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    URL: http://dx.doi.org/10.1023/A:1008365511961
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  • 40
    Electronic Resource
    Electronic Resource
    The course of long-term toxicity in patients treated with cisplatin-based chemotherapy for non-seminomatous germ-cell cancer (1999)
    Springer
    Annals of oncology 10 (1999), S. 1475-1483 
    Details
    ISSN: 1569-8041
    Keywords: chemotherapy ; cisplatin ; long-term toxicity ; testicular cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: The prognosis of advanced testicular cancer has improved considerably after the introduction of cisplatin-based combination chemotherapy. The improved prognosis of testicular cancer has brought the long-term toxicity of the treatment into focus. Patients and methods: Long-term toxicity was investigated prospectively intil more than 10 years after after treatment in a group of 22 patients treated with six series of cisplatin based chemotherapy (PVB) for testicular cancer. We have focused on nephro-, neuro-, pulmonary-, and gonadal toxicity. Results: Glomerular filtration rate (GFR) decreased significantly during treatment but increased during follow-up and all the patients had normal values of GFR 10–15 years after treatment. Carbon monoxide diffusion capacity (TLco) decreased during PVB treatment in smokers. TLco remained unchanged during the first years after PVB treatment, but improvement of TLco was seen in some patients more than 43 months after treatment. Paresthesia was reported by 83% of the patients immidiately after treatment, 50% at follow-up 4–9 years after chemotherapy and 14% prevalence 11–15 hears after treatment. The reported decline in neurotoxicity was verified by normalisation of vibration perception. Gonadal toxicity was severe and persistent although improvement was seen in a few patients even many years after treatment. Conclusions: The patients treated with PVB were physically and socially well-being at follow-up investigation 11–15 years after treatment. Improvements in pulmonary- and renal function, and recovery from neurotoxicity was seen during the long-term follow-up periode. Gonadal toxicity was severe and persistent.
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    URL: http://dx.doi.org/10.1023/A:1008322909836
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  • 41
    Electronic Resource
    Electronic Resource
    Paclitaxel and gemcitabine in advanced non-nasopharyngeal head and neck cancer: A phase II study conducted by the Hellenic Cooperative Oncology Group (1999)
    Springer
    Annals of oncology 10 (1999), S. 475-478 
    Details
    ISSN: 1569-8041
    Keywords: chemotherapy ; gemcitabine ; head and neck tumors ; paclitaxel
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Paclitaxel as monotherapy or in combination with other drugs has demonstrated significant activity in patients with squamous cell carcinoma of the head and neck region (SCCHN). Preclinical studies have shown gemcitabine to be highly active in SCCHN cell lines. Purpose of the study: To evaluate the activity and toxicity of the combination of paclitaxel by three-hour infusion and gemcitabine as first-line chemotherapy in patients with recurrent and/or metastatic head and neck cancer (HNC). Patients and methods: From September 1996 until May 1998, 44 patients with non-nasopharyngeal recurrent and/or metastatic HNC entered the study. There were 37 men and seven women with a median age of 61 years (range 35–79) and a median performance status of 1 (range 0–2). The location of the primary tumor in the majority of them was either the larynx or the oral cavity. Treatment consisted of six cycles of gemcitabine 1100 mg/m2 over 30 min on days 1 and 8 immediately followed on day 1 by paclitaxel 200 mg/m2 by three-hour infusion. The treatment was repeated every three weeks. Results: Twenty-four (55%) patients completed all six cycles of treatment. A total of 205 cycles were administered, 165 (81%) of them at full dose. The median relative dose intensity (DI) of gemcitabine was 0.93 and of paclitaxel 0.95. Except for alopecia, which was universal, grade 3–4 toxicities included neutropenia (21%), thrombocytopenia (5%), anemia (5%), infection (5%), flu-like syndrome (5%) and peripheral neuropathy (2%). Five (11%) patients achieved complete and 13 (30%) partial responses, for an overall response rate of 41%. After a median follow-up of 13 months, the median time to progression was four months and median survival nine months. Conclusions: The combination of paclitaxel and gemcitabine is active and well tolerated in patients with recurrent and/or metastatic HNC – randomized studies comparing this combination with other regimens are warranted.
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    URL: http://dx.doi.org/10.1023/A:1008397424359
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  • 42
    Electronic Resource
    Electronic Resource
    Vinorelbine as first-line chemotherapy for advanced breast cancer in women 60 years of age or older (1999)
    Springer
    Annals of oncology 10 (1999), S. 397-402 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; old age ; vinorelbine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Older patients with advanced breast cancer are less likely to receive chemotherapy than younger patients. Vinorelbine is an attractive alternative in this setting because of its clinical activity and low frequency of side effects. This multicenter, phase II trial was designed to assess the safety and efficacy of intravenous vinorelbine as first-line therapy in women ≥60 years old. Patients and methods: Fifty-six women (median age, 72 years; range 60–84 years), with measurable advanced breast cancer and no prior chemotherapy for metastatic disease, were enrolled and included in the analysis. Vinorelbine 30 mg/m2 was administered weekly for 13 weeks and then every two weeks until development of progressive disease; doses were reduced or delayed to manage toxicity. Results: The objective response rate was 38% (95% confidence interval (95% CI): 24%–51%); median duration of response, nine months; median time to disease progression in all patients, six months. The major dose-limiting toxicity was hematologic, which led to a median dose intensity of 20.6 mg/m2/week. Grade 3–4 nonhematologic toxicity consisted of asthenia (7%); nausea and generalized pain (5%); vomiting, chest pain, abdominal pain, and elevated AST (4%); fever, diarrhea, constipation, and injection site reaction (2%). Neurotoxicity and alopecia were grade 1–2 and relatively infrequent. Conclusions: Vinorelbine offers a promising alternative for the management of advanced breast cancer in elderly patients who are concerned about the subjective side effects of cytotoxic chemotherapy. The dose-limiting toxicity is neutropenia, which is readily managed with dose adjustment. Nonhematologic toxicity, including gastrointestinal side effects, is minimal. Randomized studies are warranted to compare the activity of vinorelbine with that of other regimens in elderly patients.
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    URL: http://dx.doi.org/10.1023/A:1008364222793
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  • 43
    Electronic Resource
    Electronic Resource
    Phase II trial combining mitomycin with 5-fluorouracil, epirubicin, and cisplatin in recurrent and metastatic undifferentiated carcinoma of nasopharyngeal type (1999)
    Springer
    Annals of oncology 10 (1999), S. 421-425 
    Details
    ISSN: 1569-8041
    Keywords: chemotherapy ; mitomycin ; recurrent ; undifferentiated carcinoma of nasopharyngeal type
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: This phase-II study was conducted to investigate the potential benefit from the addition of mitomycin to a conventional anthracycline-cisplatin- and 5-fluorouracil-based chemotherapy for recurrent and metastatic undifferentiated carcinoma of nasopharyngeal type (UCNT). Patients and methods: Between July 1989 and December 1991, 44 consecutive patients (M/F 36/8; median age: 45, range 20–72; performance status (PS) 0: 20 patients, PS 1: 14 patients, PS 2: 10 patients) with recurrent or metastatic UCNT were entered in this study after complete clinical, biological, and radiological pre-therapeutic work-ups. Chemotherapy (FMEP regimen) consisted of 800 mg/m2/day 5-fluorouracil in continuous infusion from day 1 to day 4 combined with 70 mg/m2 epirubicin, 10 mg/m2 mitomycin, and 100 mg/m2 cisplatin on day 1, every four weeks for six cycles. Mitomycin was delivered in cycles 1, 3, and 5 only. Eleven patients had isolated loco-regional recurrences, 12 patients had local recurrences associated with distant metastasis, and 21 patients had metastasis only. Toxicity and response were evaluated according to WHO criteria. Toxicity: Grade 3–4 neutropenia was observed in 122 of 212 evaluable cycles (57%) and 39 of 44 patients (89%); febrile neutropenia occurred in 16 patients (36%) and 24 cycles (11.3%). Grade 3–4 thrombocytopenia was observed in 27 patients (61%) and 45 cycles (21%), including 27 of 45 cycles (60%) with mitomycin. Grade 3 anemia was noted in 18 patients (40%) and 23 cycles (11%), including 18 of 23 cycles (78%) with mitomycin. Grade 3–4 mucositis occurred in 25 cycles (11%) and 14 patients (32%), mainly in those previously treated with radiation therapy in the head and neck area. There were four treatment-related deaths (9%); three of them neutropenia-related, and one of cardiac toxicity. Response: Forty-four patients were evaluable for response: There were 23 of 44 objective responses (52%), including six complete responses (13%), and 17 partial responses (38%). Additional radiotherapy was given to 13 patients after documentation of response: Nasopharyngeal tumor + cervical nodes (eight patients) and/or on bone metastasis sites (five patients); mediastinal lymph nodes (one patient). At a median follow-up of 87 months (range 71–100), five patients are alive and in continuous complete remission. The median survival time was 14 months and the median time to progression nine months. Conclusion: The regimen under study is active in recurrent/metastatic UCNT, but associated with excessive toxicity.
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    URL: http://dx.doi.org/10.1023/A:1008342828496
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  • 44
    Electronic Resource
    Electronic Resource
    Phase I study of the sequential administration of edatrexate and paclitaxel in patients with advanced solid tumors (1999)
    Springer
    Annals of oncology 10 (1999), S. 601-603 
    Details
    ISSN: 1569-8041
    Keywords: chemotherapy ; edatrexate ; paclitaxel ; synergism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: The antifolate edatrexate and the microtubule-stabilizing agent paclitaxel have both demonstrated single-agent activity in lung and breast cancer. In vitro, the sequential combination of edatrexate followed by paclitaxel produced synergistic antitumor effects. This trial was designed to find the maximum tolerated doses of edatrexate and paclitaxel when given every two weeks utilizing this sequential schedule. Patients and methods: Thirty-four patients with solid tumors received edatrexate intravenously on days 1 and 15 and paclitaxel intravenously as a three-hour infusion on days 2 and 16 of each 28-day cycle. Edatrexate was escalated from 40 to 120 mg/m2 and the paclitaxel dose fixed at 135 mg/m2. When the maximum-tolerated dose was not reached, edatrexate was fixed at 120 mg/m2 and paclitaxel escalated to 175 and 210 mg/m2. Results: All 34 patients were assessable. The maximum tolerated doses were 120 mg/m2 of edatrexate and 210 mg/m2 of paclitaxel. Grade 3 myalgia, peripheral neuropathy, leukopenia, and an infusion-related reaction occurred. Eight patients with non-small-cell lung cancer and one with bladder cancer achieved major objective responses. Conclusions: The recommended phase II doses are 120 mg/m2 of edatrexate days 1 and 15 and 175 mg/m2 of paclitaxel as a three-hour infusion days 2 and 16 of a 28 day cycle. These results warrant phase II trials of the combination leading to phase III studies comparing the two drugs to a single agent to confirm the preclinical evidence of synergy.
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    URL: http://dx.doi.org/10.1023/A:1026404812699
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  • 45
    Electronic Resource
    Electronic Resource
    Chemotherapy for brain metastases of lung cancer: A review (1999)
    Springer
    Annals of oncology 10 (1999), S. 753-759 
    Details
    ISSN: 1569-8041
    Keywords: chemotherapy ; brain metastases ; lung cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In lung cancer patients brain metastases develop with a high frequency. For years radiotherapy has been the standard treatment for these patients. Here we review the experience with chemotherapy for brain metastases in lung cancer patients. The concept of the brain as pharmacological sanctuary site when brain metastases are present is challenged and it is argued that chemotherapy does play a role in this situation. Recent clinical trials indicate that the combination of chemotherapy and radiotherapy may become the standard treatment for lung cancer patients with brain metastases. It is unclear whether for micrometastatic disease to the brain, blood brain barrier function is of importance for the outcome of chemotherapy in lung cancer patients with respect to the development of overt brain metastases. Areas of improvement of delivery of cytotoxic agents to the brain when brain metastases have not yet developed are discussed.
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    URL: http://dx.doi.org/10.1023/A:1008318515795
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  • 46
    Electronic Resource
    Electronic Resource
    A phase I study of sequential vinorelbine followed by paclitaxel (1999)
    Springer
    Annals of oncology 10 (1999), S. 861-863 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; paclitaxel ; phase I ; vinorelbine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: In vitro experiments suggest that administration of vinorelbine preceding paclitaxel results in synergistic cytotoxic effects. A phase I dose escalation trial of vinorelbine daily × 3 with paclitaxel on day 3 repeated every 28 days in metastatic breast cancer patients was completed. Patients and methods: Female patients, PS 0–2, without evidence of CNS disease or prior neuropathies were treated with vinorelbine at dose levels 7, 10, 13 mg/m2 per day and paclitaxel over three hours at dose levels of 135, 175, and 200 mg/m2. Results: Twenty-eight patients with six dose levels were studied. At dose level 1, patients developed intolerable but reversible neutropenia. Subsequent dose levels required filgrastim. Dose limiting toxicities were myalgia and fatigue at vinorelbine 13 mg/m2 /day and paclitaxel 200 mg/m2. Neuropathy was minor. Twelve of twenty-five patients with measurable disease had a rapid response which did not correlate with dose level. Conclusions: Sequential administration of these two agents demonstrates activity in breast cancer patients. Phase II dosing on this schedule should be vinorelbine 13 mg/m2/day × 3 and paclitaxel 175 mg/m2. With proper selection of patients, concern about neurologic toxicity should not impede future trials of vinorelbine with paclitaxel.
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    URL: http://dx.doi.org/10.1023/A:1008351915582
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  • 47
    Electronic Resource
    Electronic Resource
    Docetaxel and cisplatin: An active regimen in patients with locally advanced, recurrent or metastatic squamous cell carcinoma of the head and neck (1999)
    Springer
    Annals of oncology 10 (1999), S. 119-122 
    Details
    ISSN: 1569-8041
    Keywords: chemotherapy ; cisplatin ; docetaxel ; head and neck cancer ; phase II
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Docetaxel and cisplatin are among the most active antitumor agents in head and neck cancer, and phase I studies found the combination of the two drugs to be feasible. The EORTC ECSG performed a multicenter phase II study in patients with locally advanced, recurrent or metastatic squamous cell carcinoma of the head and neck to evaluate the antitumor efficacy and toxicity of this combination. Patients and methods: Eligibility criteria included written informed consent, a WHO performance status 〈2, life expectancy of 〉12 weeks, and adequate bone marrow, liver and renal function. Neoadjuvant pretreatment with cisplatin-based chemotherapy or prior radiotherapy were allowed. Patients were ineligible if pretreated with taxoids, had CNS involvement, concurrent malignancy, peripheral neuropathy, or no measurable disease. Treatment consisted of docetaxel 100 mg/m2 (one-hour i.v. infusion), followed by cisplatin 75 mg/m2 (three-hour i.v. infusion), repeated every three weeks. Supportive care included hydration, 5HT3- antagonists, and corticosteroids. Results: Forty-four patients (median age 55 years, range 35–76) entered the trial; 41 patients were eligible, 164 cycles of treatment were evaluable for toxicity, and 31 patients for response. Fourteen patients had undergone prior surgery, 15 had received radiotherapy, and five had had chemotherapy. A median number of four treatment cycles (range 1–6) was given. Hematologic and non-hematologic toxicities were common, but hypersensitivity reactions and fluid retention were very infrequent due to corticosteroid prophylaxis. Four patients were taken off the study due to toxicity, and one toxic death occurred due to pneumonia. Among 41 eligible patients, objective responses as confirmed by independent review included six complete remissions and 16 partial remissions, resulting in an overall response rate of 53.7% (95% confidence interval: 37.4%–69.3%). Responses occurred in locally advanced, recurrent and metastatic disease, both in pre- and non-pretreated patients. Of 22 evaluable, non-pretreated patients with locally advanced or metastatic disease, five achieved complete responses, and 14 partial responses. Observed among nine evaluable pretreated patients with locally advanced or metastatic head and neck cancer were one complete response and two partial responses. Conclusion: The combination of docetaxel and cisplatin is feasible and active in locally advanced, recurrent, and metastatic squamous cell carcinoma of the head and neck.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008360323986
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  • 48
    Electronic Resource
    Electronic Resource
    The influence of familial and hereditary factors on the prognosis of breast cancer (1999)
    Springer
    Annals of oncology 10 (1999), S. 1163-1170 
    Details
    ISSN: 1569-8041
    Keywords: BRCA1 ; BRCA2 ; breast cancer ; family history ; survival
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Family history is a well recognized risk factor for breast cancer, but its impact in terms of breast cancer survival is uncertain. The recent identification of breast cancer predisposing genes has provided new clinical insights in this field. Design: English literature identified through Medline between 1976 and February 1999 was reviewed including search terms: breast cancer, survival, prognosis, family history, genetics, BRCA1, BRCA2, and related articles. Results: Publications were divided into three categories.Family history-based studies: eighteen articles were reviewed. Four studies showed a statistically significant better survival in patients with a family history of breast cancer, and two studies demonstrated a significantly worse prognosis in this context. The remaining articles showed no significant difference. Linkage studies: Two studies based on linkage to BRCA1 found that overall survival was better in linked families. A third one concluded to a worse outcome in BRCA2-linked tumors. Mutation-based studies: 10 studies looking at the association between germ-line mutations in BRCA1/BRCA2 and clinical outcomes were reviewed. Eight articles reported no significant difference in outcome, whereas two studies showed a worse outcome in patients with mutations. Conclusions: Conflicting data exist as to whether the prognosis of familial or hereditary breast cancer differs from that of sporadic cases. Some of the discrepancies may be explained by methodological differences or biases. However, no studies showed a survival advantage for BRCA1mutation carriers. This seems to indicate that BRCA1-related breast cancer is not associated with a survival advantage, and that in fact, certain BRCA1 germline mutations confer a worse prognosis. However, to adequately answer this question, more efficient molecular tools to identify all the genetic changes responsible for breast cancer predisposition, and large cohort studies to evaluate their clinical consequences, are needed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008301314812
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  • 49
    Electronic Resource
    Electronic Resource
    A phase II study of the modulation of 5-fluorouracil and folinic acid with high-dose infusional hydroxyurea in metastatic colorectal carcinoma (1999)
    Springer
    Annals of oncology 10 (1999), S. 981-983 
    Details
    ISSN: 1569-8041
    Keywords: chemotherapy ; colorectal cancer ; 5-fluorouracil ; folinic acid ; hydroxyurea ; modulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Hydroxyurea (HU), an inhibitor of ribonucleotide reductase, may potentiate the activity of 5-fluorouracil (5-FU) and folinic acid (FA) by reducing the deoxyribonucleotide pool available for DNA synthesis and repair. However as HU may inhibit the formation of 5-fluoro-2′-deoxyuridine-5′-monophosphate (FdUMP), one of the principal active metabolites of 5-FU, the scheduling of HU may be critical. In vitro experiments suggest that administration of HU following 5-FU, maintaining the concentration in the region of 1 mM for six or more hours, significantly enhances the efficacy of 5-FU. Patients and methods: 5-FU/FA was given as follows: days 1 and 2 – FA 250 mg/m2 (max. 350 mg) over two hours followed by 5-FU 400 mg/m2 by intravenous bolus (ivb) over 15 minutes and subsequently 5-FU 400 mg/m2 infusion (ivi) over 22 hours. HU was administered on day 3 immediately after the 5-FU with 3 g ivb over 15 minutes followed by 12 g ivi over 12 hours. Results: Thirty patients were entered into the study. Median survival was nine months (range 1–51+ months). There were eight partial responses (28%, 95% CI: 13%–47%). The median duration of response was 6.5 (range 4–9 months). Grade 3–4 toxicities included neutropenia (grade 3 in eight patients and grade 4 in five), anaemia (grade 3 in one patient) and diarrhoea (grade 3 in two patients). Neutropenia was associated with pyrexia in two patients. Phlebitis at the infusion site occurred in five patients. The treatment was complicated by pulmonary embolism in one patient and deep venous thrombosis in another. Conclusion: HU administered in this schedule is well tolerated. Based on these results and those of other phase II studies, a randomised phase III study of 5-FU, FA and HU versus 5-FU and FA using the standard de Gramont schedule is recommended.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008330302535
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  • 50
    Electronic Resource
    Electronic Resource
    ESTIC position paper: High-dose chemotherapy for breast cancer, investigation should continue (1999)
    Springer
    Annals of oncology 10 (1999), S. 903-905 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; high-dose chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008396811371
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  • 51
    Electronic Resource
    Electronic Resource
    Paclitaxel, gemcitabine, and cisplatin in non-resectable non-small-cell lung cancer (1999)
    Springer
    Annals of oncology 10 (1999), S. 1043-1049 
    Details
    ISSN: 1569-8041
    Keywords: chemotherapy ; non-small cell lung cancer ; NSCLC ; three-drugs combination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Paclitaxel, gemcitabine, and cisplatin are each active in non-small-cell lung cancer (NSCLC), and with different modes of action. Hence, a phase II study combining these drugs were conducted. Patients and methods: Treatment was paclitaxel 110 mg/m2 and cisplatin 60 mg/m2 day 1 and 15, with gemcitabine 800 mg/m2 day 1, 8, and 15, every four weeks. Patients had previously untreated NSCLC, measurable disease, age 18–70 years, performance status ≤2, and no brain metastases. Results: Among 49 patients, 6 (group 1) received chemotherapy as described above, while 43 patients (group 2) did not receive gemcitabine day 8. In group 1, all experienced grade 4 neutropenia and four achieved a partial response (67%). In group 2, neutropenia grade 4 occured in 58%, with one episode of febrile neutropenia and no toxic death. No other grade 4 toxicities occured, while grade 3 toxicity occured with respect to thrombocytopenia (9%), nausea/vomiting (12%), neurotoxicity (12%), and nephrotoxicity (7%). There were 3 complete and 20 partial responses (response rate 54%, 95% confidence limits 38%–69%), median response duration 29 weeks (range 10–66+), median time to progression 28 weeks (range 4–66+), median survival 46 weeks (4–89+) and one-year survival rate 42%. Conclusion: This regimen of paclitaxel, gemcitabine, and cisplatin has neutropenia as dose limiting toxicity, but septicemic episodes were rare and toxic death did not occur. Other grade 4 toxicities than neutropenia did not occur. The regimen appears safe and with a noteworthy activity both in terms of response rate, time to progression, and survival.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008352900990
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  • 52
    Electronic Resource
    Electronic Resource
    Current Chemotherapeutic Possibilities in Pancreaticobiliary Cancer (1999)
    Springer
    Annals of oncology 10 (1999), S. 157-161 
    Details
    ISSN: 1569-8041
    Keywords: chemotherapy ; 5-fluorouracil ; gemcitabine ; pancreatic cancer ; pancreaticobiliary cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract At time of presentation the majority of patients with pancreaticobiliary cancer have locally advanced or metastatic disease which makes them unamenable for curative surgery. In these patients chemotherapy is an option which has gained more support over the past few years. Special problems faced in chemotherapeutic treatment are the patient's poor condition and the difficulties faced in evaluating response. 5-FU has been the only drug with some efficacy for a long time, but more recently gemcitabine appeared to be more efficient. In locally advanced pancreatic cancer the combination of chemotherapy with radiotherapy has not gained much support. However, studies are implicating better local control with combined treatment and recurrences appear more often at distant sides. In some cases irresectable tumors became resectable. Because of the poor survival after surgery with curative intent, adjuvant and neoadjuvant therapy are becoming important issues. Although studies of adjuvant therapy suggest benefit, research is seriously hampered by poor patient accrual due to the morbidity of pancreaticoduodenectomy. Neoadjuvant treatment may overcome this problem. Until now there has been only modest improvement in the treatment of pancreatic cancer. Hopefully, new treatment modalities such as immunotherapy, gene therapy and antiangiogenic therapy will alter this dismal picture. In biliary cancer the role of chemotherapy is less well defined, since only few studies with low patients numbers have been performed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008342315262
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  • 53
    Electronic Resource
    Electronic Resource
    Experimental Drugs and Drug Combinations in Pancreatic Cancer (1999)
    Springer
    Annals of oncology 10 (1999), S. 234-238 
    Details
    ISSN: 1569-8041
    Keywords: chemotherapy ; 5-fluorouracil ; gemcitabine ; pancreatic carcinoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The current role of chemotherapy in pancreatic cancer is limited. Chemotherapy usually consists of 5-fluorouracil (5FU) and gemcitabine either as a single agent or in combinations. However, response rates are below 15% with minor effects on overall survival. Due to the aggressive behavior of the disease, current emphasis of new experimental chemotherapy is also focusing on clinical benefit: improvement of pain, performance status or weight. The results with gemcitabine indicated that evaluation of new chemotherapeutic agents in pancreatic cancer should not be limited to the evaluation of response rates; single agent gemcitabine not only showed higher response rates than 5FU, but also resulted in clinical benefit for the patients. Several new agents have been introduced into the clinic for treatment of various gastro-intestinal malignancies, whereas novel agents with different types of targets, such as marimastat deserve further attention. Several oral formulations of 5FU, such as capecitabine, UFT, and eniluracil with 5FU, aim to simulate long-term continuous infusion. Response rates of these formulations are comparable to those of 5FU continuous infusion and 5FU bolus injections. However, the convenience of oral administration with reliable plasma drug concentrations makes these agents very attractive as a replacement of traditional 5FU administration. Since 5FU acts by inhibition of thymidylate synthase (TS), resulting in inhibition of DNA synthesis, several new antifolates, directed towards TS, have been developed. However, these agents, such as ZD1694 (Tomudex, Raltitrexed) and LY231514 (MTA, multitargetted antifolate) showed only limited efficacy. Other new agents active in colorectal cancer, e.g. the topoisomerase I inhibitors topotecan and CPT-11, showed only minor activity. The same was observed for the taxanes. Combinations of gemcitabine (cisplatin, 5FU, epirubicin, marimastat) show promising activities, not only regarding response but also with respect to clinical benefit. The effects were better than that for each agent separately. Thus, despite limited activity of single agents, novel combinations especially with gemcitabine are promising, with emphasis on improvement of the clinical benefit of patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008399927983
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  • 54
    Electronic Resource
    Electronic Resource
    Chemotherapy of Advanced Non-Small Cell Lung Cancer (1999)
    Springer
    Annals of oncology 10 (1999), S. 77-82 
    Details
    ISSN: 1569-8041
    Keywords: chemotherapy ; non-small cell lung cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Until recently the role of chemotherapy in NSCLC has generally been questioned. Major concerns included marginal activity, considerable toxicity and high cost of this treatment. There has, however, been increasing evidence from individual studies and meta-analyses that chemotherapy in advanced NSCLC is able to increase survival and improve quality of life. In the past few years a series of active drugs (paclitaxel, docetaxel, gemcitabine, vinorelbine, topotecan and irinotecan) with novel mechanisms of action and favourable toxicity profiles have been developed. These agents appear to hold the promise of added therapeutic benefit. In consequence, chemotherapy has currently been considered an important part of the standard treatment in selected patients with advanced NSCLC. Despite recent developments, treatment outcomes in advanced NSCLC remain far from satisfactory, and new effective means are desperately needed if more patients are to enjoy the prospects of long-term survival.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008377529788
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  • 55
    Electronic Resource
    Electronic Resource
    Intravenous and Intra-Arterial Chemotherapeutic Possibilities in Biliopancreatic Cancer (1999)
    Springer
    Annals of oncology 10 (1999), S. 305-307 
    Details
    ISSN: 1569-8041
    Keywords: biliay tract cancer ; chemotherapy ; 5-fluorouracil ; gemcitabine ; intra-arterial chemotherapy ; pancreatic cancer ; regional chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Chemotherapy of carcinomas of the pancreas and biliary tract has always been of limited value. Pancreatic cancer is well known for its aggressive nature, poor prognosis and resistance to antineoplastic agents which are effective in other solid tumors. 5-Fluorouracil has long been the mainstay of the treatment of pancreatic cancer, although the response rate to this agent is 〈10% and the influence on survival and quality of life is neglegible. Combination chemotherapy in pancreatic cancer adds to the side effects of treatment, but has had no proven effect on effectiveness. The only new anticancer drug of which an improvement in clinical benefit has been indicated on the basis of randomized clinical research, is gemcitabine, although the magnitude of improvement is limited. Due to the rarity of tumors of the biliary tract, the data on the effect of chemotherapy in this disease is sparse but does not suggest that it leads to superior results than supportive care alone. Likewise, no literature exists supporting the routine application of regional chemotherapy infusion in these type of tumors.
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    URL: http://dx.doi.org/10.1023/A:1008361708844
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  • 56
    Electronic Resource
    Electronic Resource
    Chemotherapy for advanced pancreatic cancer: It may no longer be ignored (1999)
    Springer
    Annals of oncology 10 (1999), S. 105-109 
    Details
    ISSN: 1569-8041
    Keywords: advanced pancreatic cancer ; chemotherapy ; clinical benefit
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Two case histories are reported here in which a chemotherapeutic approach improved the clinical conditions of patients with advanced pancreatic cancer. Until recently, chemotherapy was considered ineffective in pancreatic cancer, and most oncologists treated these patients with best-supportive-care only. Enthusiasm for systemic therapy of advanced pancreatic cancer is again growing, spurred by the advent of new drugs and new treatment endpoints such as life quality and symptom palliation. Gemcitabine, the most intensively- investigated new drug in pancreatic cancer, has shown an advantage in both survival and clinical benefit over that of 5-fluorouracil (5- FU). Other new drugs such as taxanes have shown interesting levels of activity, and are deserving of further evaluation. Although these results are far from conclusive and are only partially satisfactory, they represent a significant step forward in the treatment of advanced pancreatic cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008205515591
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  • 57
    Electronic Resource
    Electronic Resource
    Epstein–Barr virus related hemophagocytic syndrome in a T- cell rich B-cell lymphoma (1999)
    Springer
    Annals of oncology 10 (1999), S. 231-234 
    Details
    ISSN: 1569-8041
    Keywords: chemotherapy ; Epstein–Barr virus ; LMP-1 ; peripheral blood stem cells ; T-cell rich B-cell non-Hodgkin's lymphoma (TCRBCL)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We report the case of a 30-year-old woman who presented with an EBV related hemophagocytic syndrome. After a few months she developed a T-cell rich B-cell non-Hodgkin's lymphoma with liver involvment. Serological data demonstrated a reactivation of the EBV infection. Tumor progression with liver involvement occured during treatment with conventional chemotherapy. Tumor reduction and disappearence of all masses was seen after starting high-dose sequential chemotherapy, followed by an autologous peripheral blood progenitor transplantation. LMP-1 could be amplified in the tumor material by PCR technology, but no LMP-1 expression could be found in the few malignant B-cells with Reed–Sternberg morphology. Sequence analysis of the carboxy terminal of the LMP-1 region revealed the naturally occuring 30 bp deletion variant of the LMP-1 with multiple point mutations within the NF kb region. Since LMP-1 was not expressed in the malignant tumor cells, no evidence could be found, that EBV participated in the tumorigenesis of this case.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008212516595
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  • 58
    Electronic Resource
    Electronic Resource
    Docetaxel in the community setting: An analysis of 377 breast cancer patients treated with docetaxel (Taxotere®) in the UK (1999)
    Springer
    Annals of oncology 10 (1999), S. 205-210 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; docetaxel
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Given as first- or second-line chemotherapy, docetaxel appears to have great potential in advanced breast cancer. Patients and methods: Three hundred and seventy-seven locally advanced or metastatic breast cancer patients received docetaxel (Taxotere®) as part of a named patient programme under the care of 108 oncologists from 61 cancer units across the UK. The recommended starting dose was 100 mg/m2, but patients at higher risk of toxicity started at 75 mg/m2. All patients received corticosteroid premedication. The modal number of prior chemotherapy regimens was 2 (range 1–7), 342 patients (91%) had at least one prior anthracycline-based regimen. Results: Response was graded according to the managing clinician's best judgement without formal criteria. The overall response rate (ORR) was 46% among the 331 evaluable patients, 46% among the 299 patients who were 'anthracycline resistant' and 35% among the 82 patients who were 'anthracycline refractory' (progressive disease being the best response obtained to the most recent anthracycline containing regimen). One hundred and ninety-three patients started at the full dose of 100 mg/m2 with an ORR of 55% and 129 started at 75 mg/m2 with an ORR of 33%. In October 1997, some two years after the programme had started, 26 of 377 patients were still alive, although no complete remissions have lasted to this date. Kaplan–Meier survival analysis yielded a median survival of 194 days (95% CI: 178–218 days). Haematological parameters were checked before each course of docetaxel and additionally as clinically indicated. The safety data confirmed that docetaxel has a manageable, predictable side effect profile; 29 of 377 (7.7%) patients were hospitalised as a result of neutropenic sepsis. Conclusions: The results of this named patient programme over a two year timespan confirm that docetaxel is an effective chemotherapy option in patients with locally advanced and/or metastatic breast cancer, including an 'anthracycline refractory' population.
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    URL: http://dx.doi.org/10.1023/A:1008370930599
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  • 59
    Electronic Resource
    Electronic Resource
    Weekly gemcitabine and cisplatin in advanced non-small-cell lung cancer: A phase II study (1999)
    Springer
    Annals of oncology 10 (1999), S. 217-221 
    Details
    ISSN: 1569-8041
    Keywords: chemotherapy ; cisplatin ; gemcitabine ; NSCLC ; weekly administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: The combination of gemcitabine and cisplatin has proven effective in the treatment of advanced non-small-cell lung cancer (NSCLC). However, the optimal schedule for administration of the two drugs has not yet been determined. In this study we evaluated the activity and toxicity of a weekly gemcitabine and cisplatin schedule. Patients and methods: Thirty-six untreated patients with stage IIIB–IV NSCLC entered the study. Treatment consisted of gemcitabine 1000 mg/m2 i.v. and cisplatin 35 mg/m2 i.v., both given weekly on days 1, 8, and 15, followed by one week of rest. Results: Ninety-seven courses (273 weekly administrations) were delivered. The median dose-intensity was 612 mg/m2 per week for gemcitabine (82%) and 21 mg/m2 per week for cisplatin (80%). All 36 of the patients were evaluable for toxicity, and 30 for response. Partial remissions were observed in 12 patients, for an overall response rate of 40% (95% confidence interval (95% CI): 22.5%–57.5%). Most of the partial remissions were seen in IIIB patients (54% of the stage IIIB and 22% of the stage IV patients responded). According to the intent-to-treat principle, the response rate was 33.3% (12 of 36 patients). The median response duration was 9.9 months (range 4–23) and the median survival time 11.8 months (range 1–24). World Health Organization (WHO) grade 3–4 myelotoxicity was: thrombocytopenia in nine patients (25%), neutropenia in six (16.6%) and anemia in six (16.6%); there was very little additional major toxicity. Conclusions: This regimen appears to be active and to have a favourable toxicity profile.
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    URL: http://dx.doi.org/10.1023/A:1008323604269
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  • 60
    Electronic Resource
    Electronic Resource
    Management of cancer in pregnancy: A case of Ewing's sarcoma of the pelvis in the third trimester (1999)
    Springer
    Annals of oncology 10 (1999), S. 345-350 
    Details
    ISSN: 1569-8041
    Keywords: chemotherapy ; Ewing's sarcoma ; pregnancy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Ewing's sarcoma of the pelvic bones was diagnosed in a 21-year childbearing woman, raising major medical and ethical problems. The diagnostic and therapeutic approaches during the sixth month of gestation were tailored in order to cure the patient and avoid unnecessary toxicity to the fetus. Ancillary tests included ultrasound and MRI studies of the pelvis. Ifosfamide and adriamycin, premedicated by granisetron, were administered during gestation, and were found to be safe. Cesarean section was the preferred way of delivery since the tumor involved the pelvic bones. The outcome was a disease-free patient and a small healthy baby who is now two years of age.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008235023749
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  • 61
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    Electronic Resource
    Hodgkin's disease in 35 patients with HIV infection: An experience with epirubicin, bleomycin, vinblastine and prednisone chemotherapy in combination with antiretroviral therapy and primary use of G-CSF (1999)
    Springer
    Annals of oncology 10 (1999), S. 189-195 
    Details
    ISSN: 1569-8041
    Keywords: antiretroviral ; chemotherapy ; granulocyte-colony stimulating factor ; HIV infection ; Hodgkin's disease ; therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: The optimal therapeutic approach for patients with Hodgkin's disease and human immunodeficiency virus infection (HD–HIV) is unknown. In an attempt to improve the results previously obtained with EBV (epirubicin, bleomycin and vinblastine) without G-CSF (Cancer 1994; 73: 437–44), in January 1993 we started a trial using chemotherapy (CT) consisting of EBV plus prednisone (EBVP), concomitant antiretroviral therapy (zidovudine, AZT or dideoxinosyne, DDI) , and G-CSF. Patients and methods: Up to August, 1997, 35 (30 M/5 F) consecutive previously untreated patients (median age 34, range 21–53 years) with HD–HIV were enrolled in the European Intergroup Study HD–HIV. Their median performance status was 1 (range 1–3). At diagnosis of HD, 26% of the patients had AIDS, 90% had B symptoms at HD presentation and 83% had advanced-stage HD. Patients received E 70 mg/m2 i.v. on day 1, B 10 mg/m2 i.v. on day 1, V 6 mg/m2 i.v. on day 1 and P 40 mg/m2 p.o. from day 1 to day 5 (EBVP). Courses were repeated every 21 days for six cycles. AZT (250 mg × 2/day), or DDI (200 or 300 mg × 2/day) if AZT had been previously used, were given orally from the beginning of CT. G-CSF was given at the dose of 5 mcg/kg/day s.c. from day 6 to day 20 in all cycles. Results: An overall response rate of 91% was observed. There were 74% complete responses (CR) and 17% partial responses (PR). Toxicity was moderate, with grade 3–4 leukopenia and thrombocytopenia in 10 (32%) and three (10%) patients, respectively. The median number of administered cycles was 6 (range 3–6). Twenty-three of 35 patients received AZT and nine patients received DDI. Three (8%) patients had opportunistic infections (OI) during or immediately after CT. The median CD4+ cell count was 219/mm3 (6–812) at HD diagnosis and 220/mm3 (2–619) after the end of combined therapy, and these numbers remained unchanged. Ten of 26 (38%) patients who achieved CR relapsed. Twenty-three patients died of HD progression alone or in association with OI, being the cause of death in 48% and 9% of patients respectively. The median survival was 16 months, with a survival rate of 32% and a disease-free survival of 53% at 36 months. Conclusions: The combined antineoplastic and antiretroviral treatment is feasible, but HD in HIV setting is associated with a more adverse prognosis than in the general population. Although the CR rate obtained was satisfactory, the relapse rate was high. Furthermore, comparison of the results of our two consecutive prospective studies demonstrated no overall improvement in the current trial with respect to the CR rate and survival.
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    URL: http://dx.doi.org/10.1023/A:1008338915945
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  • 62
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    Electronic Resource
    The third-generation non-steroidal aromatase inhibitors: A review of their clinical benefits in the second-line hormonal treatment of advanced breast cancer (1999)
    Springer
    Annals of oncology 10 (1999), S. 377-384 
    Details
    ISSN: 1569-8041
    Keywords: anastrozole ; aromatase inhibitors ; breast cancer ; hormonal therapy ; letrozole ; review ; vorozole
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Three new aromatase inhibitors have recently completed phase III evaluation as treatment of metastatic breast cancer in post-menopausal women whose disease has progressed despite tamoxifen therapy: anastrozole (ARIMIDEX, Zeneca), letrozole (FEMARA, Novartis) and vorozole (RIVIZOR, Janssen). All belong to the third generation of non-steroidal aromatase inhibitors, and each is superior to previous generations in terms of potency and selectivity. The trials that have been performed compare each agent to megestrol acetate, and letrozole and vorozole to aminoglutethimide. Although the studies are not directly comparable due to differing study designs and patient populations, it has been demonstrated each of these drugs provides single agent, once-daily, oral palliation of hormone-responsive, post-menopausal metastatic breast cancer. Letrozole is clearly more effective than megestrol acetate, and anastrozole and vorozole are possibly so. All three are better tolerated than the progestin, particularly in terms of weight gain. Both letrozole and vorozole are significantly more effective, and better tolerated than aminoglutethimide. Overall, this most recent generation of aromatase inhibitors is a clear improvement on our current standard second-line therapies. In 1999, tamoxifen remains the first choice in the hormonal therapy of breast cancer. Following tamoxifen failure, the optimal second-line hormonal therapy remains undefined, but aminoglutethimide and megestrol acetate are no longer optimal therapy in this setting. The third-generation non-steroidal aromatase inhibitors must now be compared to each other, to the steroidal aromatase inhibitors, to the pure anti-oestrogens, and to tamoxifen.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008368300827
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    Electronic Resource
    Synchronous inflammatory breast cancer and advanced ovarian carcinoma: A case with prolonged disease-free survival (1999)
    Springer
    Annals of oncology 10 (1999), S. 585-588 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; cisplatin ; ovarian cancer ; paclitaxel
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Despite the known association of these malignancies, the incidence of a synchronous presentation of breast and ovarian cancer is low, and the current literature does not address an approach to this clinical problem directly. We report a greater than 2.5 year disease-free survival in a patient treated for synchronous stage IIIB inflammatory breast cancer and stage IIIC epithelial ovarian cancer. The prolonged disease-free survival in our case may provide some guidance in this unusual clinical situation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008239124657
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  • 64
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    Phase II study of epirubicin and vinorelbine with granulocyte colony-stimulating factor: A high-activity, dose-dense weekly regimen for advanced breast cancer (1999)
    Springer
    Annals of oncology 10 (1999), S. 937-942 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; dose-intensity ; epirubicin ; G-CS/kwd〉 ; vinorelbine ; weekly schedule
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: This study was designed to explore the effectiveness and tolerability of a weekly regimen of epirubicin and vinorelbine plus granulocyte colony-stimulating factor (G-CSF). Patients and methods: Fifty-two patients with previously untreated advanced breast cancer were treated with epirubicin (25 mg/m2/week) and vinorelbine (25 mg/m2/week) with G-CSF support, for 24 consecutive weeks. Results: The median number of courses per patient was 22 (range 10–24). The administered dose intensity was 23 mg/m2 for both epirubicin and vinorelbine. Ten complete responses (19%) and 30 partial responses (58%) were obtained, for an overall response rate of 77%. None of the patients progressed during treatment. The median response duration and time to progression were both 10 months. A total of 1065 courses were assessed for toxicity. Grade 3 neutropenia was the most common toxic manifestation, (39% of patients), without febrile neutropenia or neutropenic sepsis. Two patients had grade 3 cardiac toxicity, which regressed without sequelae. Median survival was 31 months, with a median follow-up of 24 months (range 9–40). Conclusions: Owing to its effectiveness and tolerability, the weekly regimen of epirubicin and vinorelbine plus G-CSF may represent an acceptable alternative for patients with untreated metastatic breast cancer. It could be tested in the adjuvant and neoadjuvant setting.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008324329562
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  • 65
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    Electronic Resource
    Recurrent inflammation in a site of previous necrotising fasciitis during intravenous CMF chemotherapy (1999)
    Springer
    Annals of oncology 10 (1999), S. 1101-1103 
    Details
    ISSN: 1569-8041
    Keywords: chemotherapy ; necrotising fasciitis ; recurrent inflammation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We present the case history of a patient with breast carcinoma who developed repeated inflammation at the site of previous necrotising fasciitis following each cycle of intravenous CMF chemotherapy. This complication has not previously been reported.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008331511578
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  • 66
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    Electronic Resource
    Complete response of a gastric primary after a short but toxic course of ‘S-1’ (1999)
    Springer
    Annals of oncology 10 (1999), S. 1117-1120 
    Details
    ISSN: 1569-8041
    Keywords: chemotherapy ; gastric cancer ; oral fluoropyrimidine prodrug ; S-1 ; Tegafur
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We report the case of an unresected, metastatic gastric cancer, which was treated with a very short course of the oral 5-fluorouracil (5-FU) prodrug S-1. The patient had to discontinue chemotherapy during the first treatment cycle due to severe toxicity, but achieved a pathologically confirmed, long-term complete response of her primary tumour, a diffuse-type poorly differentiated adenocarcinoma.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008364601010
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  • 67
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    Electronic Resource
    Autologous stem-cell transplant after conventional dose adjuvant chemotherapy for high-risk breast cancer: Impact on the delivery of local-regional radiation therapy (1999)
    Springer
    Annals of oncology 10 (1999), S. 929-936 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; local regional therapy ; stem-cell transplantation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: High-dose chemotherapy with autologous stem-cell transplantation is used increasingly in the treatment of poor-prognosis primary breast cancer. Because these patients may be cured with standard multimodality therapy, it is important to address both the efficacy of transplantation, and its effect on the delivery of standard treatments including local radiation therapy. Patients and methods: Patients with high risk primary breast cancer were treated with high-dose cyclophosphamide and thiotepa and stem-cell transplant following surgery and conventional-dose adjuvant chemotherapy. Outcome, including sites of failure and delivery of local radiation therapy, was assessed for 103 patients. Results: Overall and disease-free survival rates at 18 months were 83% (± 4%) and 77% (± 4%) respectively. Twenty patients (19.4%) received radiation therapy prior to transplant. Of the remaining 83, 77 received radiation therapy after transplant. Overall, 5 (19.2%) of 26 first sites of recurrence were local alone. For patients receiving radiation prior to transplant, 3 of 7 (43%, 95% CI: 6%–80%) sites of first recurrence were local, while 2 of 19 (10.5%, 95% CI: 0%–24.5%) sites of first recurrence were local alone in patients receiving post-transplant radiation or no radiation. Conclusion: Transplantation does not appear to significantly compromise the delivery or outcome of local radiation therapy for primary breast cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008393204854
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  • 68
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    Electronic Resource
    Effects of antiprogestins on the rate of proliferation of breast cancer cells (1999)
    Springer
    Molecular and cellular biochemistry 198 (1999), S. 141-149 
    Details
    ISSN: 1573-4919
    Keywords: T47D cells ; breast cancer ; cellular proliferation ; progesterone ; estradiol ; steroid receptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract We have examined the influence of progestins (progesterone, R5020) and antiprogestins (RU486, ZK98299, Org 31710 and Org 31806) on the rate of proliferation of wild type T47D cells cultured in whole fetal bovine serum (FBS) or in single charcoal stripped fetal bovine serum (SSFBS). All of the progesterone antagonists RU486, ZK98299 and two novel antiprogestins Org 31710 and Org 31806 inhibited cell proliferation when cells were cultured in FBS. In contrast, all of the antiprogestins with the exception of ZK98299 enhanced cell growth when cells were cultured in SSFBS. This stimulatory effect of RU486 was observed only at a high concentration of the ligand (1 μM). The effect of R5020, however, was concentration independent. The number of cells in the presence of RU486 was ~ 600% followed by R5020 ~ 400% above control values after a 28 day culturing period. In contrast, when the cells were grown in the presence of medium containing non-stripped whole serum, RU486 inhibited the extent of cell proliferation by 45%. Estradiol (E2) stimulated the rate of proliferation in cells cultured in SSFBS. Similar to when cells were cultured in whole serum, the antiprogestins inhibited cell growth in E2-supplemented SSFBS. Detection of the growth enhancement effects of progesterone receptor (PR) ligands such as RU486 and R5020 on the cells grown in charcoal-stripped medium appear to require the removal of E2 by charcoal stripping of the serum.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006945813508
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  • 69
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    Electronic Resource
    Ala99ser mutation in RIα Regulatory Subunit of protein kinase A causes reduced kinase activation by cAMP and arrest of hormone-dependent breast cancer cell growth (1999)
    Springer
    Molecular and cellular biochemistry 195 (1999), S. 77-86 
    Details
    ISSN: 1573-4919
    Keywords: protein kinase A ; site-directed mutagenesis ; breast cancer ; growth arrest ; cAMP response element
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Expression of the RIα regulatory subunit of protein kinase A type I is increased in human cancer cell lines, in primary tumors, in cells after transformation, and in cells upon stimulation of growth. Ala99 (the pseudophosphorylation site) of human RIα was replaced with Ser (RIα-p) for the structure-function analysis of RIα. MCF-7 hormone- dependent breast cancer cells were transfected with an expression vector for the wild-type RIα or mutant RIα-p. Overexpression of RIα-P resulted in suppression of protein kinase A type II, the isozyme of type I kinase, production of kinase exhibiting reduced cAMP activation, and inhibition of cell growth showing an increase in G0/G1 phase of the cell cycle and apoptosis. The wild-type RIα overexpression had no effect on protein kinase A isozyme distribution or cell growth. Overexpression of protein kinase A type II regulatory subunit, RIIβ, suppressed RIα and protein kinase A type I and inhibited cell growth. These results show that the growth of hormone-dependent breast cancer cells is dependent on the functional protein kinase A type I.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006934113439
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  • 70
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    Electronic Resource
    Clinical Relevance of Minimal Residual Cancer in Patients with Solid Malignancies (1999)
    Springer
    Cancer and metastasis reviews 18 (1999), S. 91-100 
    Details
    ISSN: 1573-7233
    Keywords: micrometastases ; immunohistochemistry ; minimal residual cancer ; marrow disease ; lymph node metastases ; breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract With the advent of new therapeutic modalities, the treatment options for oncologists can vary greatly depending upon the aggressiveness of the patient's cancer. Patients may receive no therapy, adjuvant therapy, aggressive adjuvant therapy (taxane based), monoclonal antibody therapy (e.g. Herceptin) or bone marrow transplantation. It is now mandatory to determine accurate prognostic patient profiles at diagnosis and during therapy to determine who would benefit most from a particular therapeutic regimen or to determine who should be shifted into more aggressive therapy. We now have ultra-sensitive methods of tumor cell detection that can determine the presence of minimal residual cancer (MRC) in marrow, stem cell product (SCP) and lymph node to help create these prognostic profiles. The author has conducted a critical review of the literature regarding the type of testing used to detect MRC, the incidence of MRC in marrow, SCP, and lymph node, and the clinical significance of MRC at diagnosis and during therapy. To date it is now clear that immunohistochemistry is a very useful diagnostic tool with adequate sensitivity to detect MRC. The presence of MRC at diagnosis in marrow and/or lymph node is associated with a poor prognosis for a number of disorders including breast cancer, neuroblastoma, gastrointestinal tumors, and lung cancer. In addition, the presence of MRC during therapy in marrow and/or SCP is associated with a very poor prognosis for patients with breast cancer. The use of testing for MRC in the patient provides prognostic information that may be of use to the oncologist.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006264420822
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  • 71
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    Increased levels of α6 integrins are associated with the metastatic phenotype of human breast cancer cells (1999)
    Springer
    Clinical & experimental metastasis 17 (1999), S. 323-330 
    Details
    ISSN: 1573-7276
    Keywords: breast cancer ; integrins ; metastasis ; progression ; xenograft model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Integrins play an important role in interactions between cells and the extracellular matrix, and thus have a potential role in metastasis. Expression levels of α6, β1 and β4 integrin sub-units were measured in a panel of human breast cancer cell lines by RT/PCR, immunoprecipitation and flow cytometry. All the lines expressed α6, with the highest levels in the MDA-MB-231 and MDA-MB-435 cells. These grew the most aggressively and were metastastic in nude mice. Low levels of α6 protein were measured in breast cancer cells that were poorly tumorigenic and non-metastatic in nude mice, and there was an inverse relationship between ER and α6 expression. RT/PCR revealed that all lines expressed the 2 isoforms of α6, with the α6A isoform generally more abundant than α6B isoform. Clones of MDA-MB-435 were isolated by sterile sorting for cells with high or low α6 expression, and two variants established from metastases in nude mice were found to differ in α6 expression. When injected into nude mice, the α6-high variants produced significantly more lung metastases than the α6-low variants. β1 was abundant in all lines, while β4 was not detected in MDA-MB-134 cells, and in the MDA-MB-435 cells an alternately spliced variant of β4 was identified. Sequencing of the alternate variant revealed a novel sequence from a splicing event in the cytoplasmic tail of β4. None of the cells with this variant mRNA expressed detectable levels of β4 protein. Our results suggest that high α6 expression in human breast cancer cells is associated with tumorigenicity and metastatic potential.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006659230585
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  • 72
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    Electronic Resource
    Chemokines induce the cellular migration of MCF-7 human breast carcinoma cells: Subpopulations of tumour cells display positive and negative chemotaxis and differential in vivo growth potentials (1999)
    Springer
    Clinical & experimental metastasis 17 (1999), S. 389-396 
    Details
    ISSN: 1573-7276
    Keywords: breast cancer ; chemokine ; integrin ; metastasis ; migration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We previously reported that chemotactic cytokines (chemokines) induce the directional migration of cells derived from the breast carcinoma cell line MCF-7 in vitro, however it was apparent that only a small percentage of cells displayed the ability to migrate upon stimulation. In the present study three sub-lines derived from the parental MCF-7 cell line were selected for their ability to migrate in response to MIP-1α, MIP-1β or RANTES across Transwell filters of 8 μm pore size. The first round selection of migratory cells resulted in sub-populations which demonstrated an increased chemotactic response compared with parental cells. Cells migrating to MIP-1β were subjected to four further rounds of positive or negative selection, resulting in two sub-lines, MCF-7L4 and MCF-7U4 which displayed an increased and decreased chemotactic response respectively to MIP-1α MIP-1β and RANTES. No difference in chemokine receptor RNA message expression between these sub-lines and the parental MCF-7 line were detected, although increased levels of α3, α6 and αv integrin sub-units were shown for MCF-7L4 (positively selected sub-line) compared with MCF-7U4 cells. Moreover, the in vivo growth of cells derived from the two MCF-7 sub-lines was inversely correlated with their chemotactic response. The results of this study depict further the inherent heterogeneity in cancer, suggesting that the chemotactic response may influence the migratory traits of sub-populations within the tumour and potentially contribute to their in vivo behavior, growth and survival.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006657109866
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  • 73
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    Electronic Resource
    N-linked oligosaccharides and metastatic propensity in in vivo selected mouse mammary adenocarcinoma cells (1999)
    Springer
    Clinical & experimental metastasis 17 (1999), S. 437-444 
    Details
    ISSN: 1573-7276
    Keywords: breast cancer ; carbohydrate ; glycosylation ; invasion ; metastasis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Studies using metastatic variant selected in vivo from a cloned parental cell line demonstrate that the expression of β1-6 branched, N-linked carbohydrates and sialic acid were positively associated with in vitro invasiveness and inversely associated with metastatic potential, adherence, and in vivo growth rate. These results suggest that at least within one tumor model, a negative association occurs between metastatic potential and β1-6 branched oligosaccharide expression. In these studies two metastatic variants, Cl-66M1 and Cl-66M2, were selected following serial in vivo passage of Cl-66, a clonal cell line obtained from a mouse mammary adenocarcinoma cell line. The parent cell line and the two metastatic variants were approximately equal in their adherence to fibronectin, laminin, and collagen type IV coated plastic. In contrast, both Cl-66M1 and Cl-66M2 had a significantly increased ability to invade through matrigel invasion chambers and expressed significantly increased levels of β1-6 branched, N-linked carbohydrates, and sialic acid compared to the clonal parental cell line, Cl-66. Furthermore, the in vivo tumor growth rates of these selected variants were decreased compared to Cl-66 with the longest tumor volume doubling time observed with Cl-66M2.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006629119030
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  • 74
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    Electronic Resource
    A novel orthotopic model of breast cancer metastasis to bone (1999)
    Springer
    Clinical & experimental metastasis 17 (1999), S. 163-170 
    Details
    ISSN: 1573-7276
    Keywords: bone metastasis ; breast cancer ; model ; PTHrP
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Breast cancer affects approximately one woman in twelve and kills more women than any other cancer. If detected early, patients have a five year survival rate of 66%, but once metastatic disease has developed, there is no effective treatment. About 70% of patients with metastatic disease have bone involvement, while lungs and liver are the other common targets. Bone metastases cause severe pain, pathological fractures and hypercalcaemia and thus are a significant clinical problem. The development of new therapies for metastatic breast carcinoma depends on a better understanding of the mechanism of homing of the tumour cells to bone, liver and lungs and the factors required for their growth in these organs. Research on mechanisms of breast cancer metastasis, particularly to bone, has relied on in vitro studies or on tumour models in which the inoculation route is designed to promote delivery of tumour cells to a specific organ. Metastases in bone are achieved by inoculation into the right ventricle of the heart. To our knowledge there has been no report of a model of metastatic spread from the mammary gland to distant sites which reliably includes bone. In this paper, we describe our recent development of a novel murine model of metastatic breast carcinoma. The new model is unique in that the pattern of metastatic spread closely resembles that observed in human breast cancer. In particular, these murine breast tumours metastasise to bone from the primary breast site and cause hypercalcaemia, characteristics not normally found in murine tumours, but common in human disease. Furthermore, in a preliminary characterisation of this model, we show that secretion of parathyroid hormone-related protein, a role for which has been implicated in breast cancer spread to bone, correlates with metastasis to bone. This model therefore provides an excellent experimental system in which to investigate the factors that control metastatic spread of breast cancer to specific sites, particularly bone. The special advantage of this system is that it involves the whole metastasis process, beginning from the primary site. Existing models consider mechanisms that pertain to growth of tumour once the site has been reached. An understanding of the regulation of these factors by potential therapeutic agents could lead to improvement in therapies designed to combat metastatic disease. For the first time, this development will allow exploration of the molecular basis of site-specific metastasis of breast cancer to bone in a clinically relevant model.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006689719505
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  • 75
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    Electronic Resource
    Mycoplasma-Mediated Uptake of the Exogenous Human BRCA1 Gene by Hatching Blastocysts (1999)
    Springer
    Journal of assisted reproduction and genetics 16 (1999), S. 546-550 
    Details
    ISSN: 1573-7330
    Keywords: breast cancer ; mycoplasma ; Ureaplasma urealyticum ; foreign DNA ; gene transfer ; transgenic
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: Biological vectors for cell transfection are mainly viral in origin, with inherent shortcomings. Mycoplasmas are ubiquitous organisms that traverse cells easily. The objective was to determine if Ureaplasma urealyticum (T-mycoplasma) would vector exogenous BRCA1 DNA into blastocysts. Methods: Hatching mouse blastocysts (N = 70) were incubated in the presence of either viable or dead Ureaplasma urealyticum at 37°C for 1 hr. The blastocysts were exposed to human BRCA1 DNA lacking homology in the mouse genome for 2 hr, followed by DNase-I treatment and wash. Polymerase chain reaction and agarose gel electrophoresis analysis of amplified products were performed. Results: The BRCA1 gene was detected in the blastocysts only when viable Ureaplasma was present. PCR analyses of control Ureaplasma and untreated blastocysts were negative. Conclusion: Viable Ureaplasma organisms were shown to mediate the uptake of DNA fragments into blastocysts, resulting in transgenic mouse blastocysts with a normal human BRCA1 exon 11 gene.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1020553322073
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  • 76
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    Electronic Resource
    Loss of heterozygosity in BRCA1 and BRCA2 markers and high‐grade malignancy in breast cancer (1999)
    Springer
    Breast cancer research and treatment 53 (1999), S. 9-17 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; microsatellites ; prognostic factors ; 17q21 region ; 13q12‐13 region
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Loss of heterozygosity (LOH) in loci of the 17q21 and 13q12‐13 regions can collaborate in the inactivation of BRCA1, BRCA2, and possibly other genes implicated in the pathogenesis of breast carcinomas. We investigate allelic losses in microsatellites of the BRCA1 and BRCA2 regions, and their correlations with seven pathologic parameters in 140 breast carcinomas. Those cases showing LOH in the region of the RB gene, 13q14, were excluded from the study. The LOH analysis was performed by amplifying DNA by PCR, using four markers of the 17q21 region (D17S856, D17S855, D17S1323, and D17S1327) and four markers of the 13q12‐13 region (D13S290, D13S260, D13S310, and D13S267). LOH in the BRCA1 region was found in 47% of tumors, correlating significantly with estrogen receptor content (p = 0.025), progesterone receptors (p = 0.004), higher grade (p = 0.0008), peritumoral vessel invasion (p = 0.001), and lymph node metastases (p = 0.002). When we excluded the cases with LOH in the BRCA2 region and those not informative for it, the significance disappeared. In the BRCA2 region, a rate of LOH of 51% was found; it correlated significantly with estrogen receptor content (p = 0.002), progesterone receptors (p =0.03), peritumoral vessel invasion (p = 0.005), higher grade (p =0.002), and lymph node metastases (p = 0.001). When cases with BRCA1 losses and those not informative were excluded, again the significance disappeared. Concomitant losses in the BRCA1 and BRCA2 regions were found in 32% of cases, correlating significantly with lymph node metastases (p = 0.0002), estrogen receptor content (p = 0.003), progesterone receptors (p = 0.001), histologic grade (p =0.01), and peritumoral vessel invasion (p = 0.0004). These results suggest that concomitant losses in both regions could have a functional effect, influencing the presence of a poor tumor pathophenotype in breast carcinomas.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006082117266
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  • 77
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    Comparative analysis of breast cancer recurrence risk for patients receiving or not receiving adjuvant cyclophosphamide, methotrexate, fluorouracil (CMF). Data supporting the occurrence of ‘cures’ (1999)
    Springer
    Breast cancer research and treatment 53 (1999), S. 209-215 
    Details
    ISSN: 1573-7217
    Keywords: adjuvant chemotherapy ; breast cancer ; cure ; early recurrences ; late recurrences ; recurrence risk pattern
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: To comparatively analyse the risk of recurrence at given times after surgery for breast cancer patients receiving or not receiving adjuvant CMF. Patients and methods: A total of 1452 node positive patients, who entered controlled clinical trials carried out at the Milan Cancer Institute and underwent radical or modified radical mastectomy for operable breast cancer, were examined. In 575 cases no further treatment was performed, whereas 877 pts were given 6 or 12 courses of adjuvant Cyclophosphamide, Methotrexate, Fluorouracil (CMF). The recurrence risk was estimated by the event-specific hazard rate for first failure and distant metastases, and, following Efron, hazard rates were fitted by logistic regression models. Results: The hazard rate for first failure and distant metastases showed a double peaked pattern for both treated patients and controls, with a first major peak at about 18–24 months from surgery (early metastases), a second minor peak at the 5th–6th year, and a tapered plateau-like tail extending over 10 years from surgery (late metastases). As expected, the recurrence risk of CMF treated patients was lower than the corresponding risk of patients undergoing surgery only. However, the difference was highly evident for early recurrences, while it declined and disappeared afterwards. Conclusion: Our findings confirm previous reports on patients not receiving adjuvant chemotherapy, suggesting that the recurrence risk for operable breast cancer has a multipeak pattern. As far as CMF treated patients are concerned, the unchanged peak timing together with the early recurrence risk reduction in comparison to controls are much more consistent with the real nonappearance of some early recurrences (putatively ‘cured’ patients) than with the delay in their manifestation. As late relapsing patients seem to have at most marginal benefits from adjuvant CMF, ways to recognize patients doomed to have late recurrence and new ways for treating micrometastases resulting in late recurrences are required.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006134702484
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  • 78
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    Electronic Resource
    Analyzing prognostic factors in breast cancer using a multistate model (1999)
    Springer
    Breast cancer research and treatment 54 (1999), S. 83-89 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; multivariate analysis ; multistate model ; prognostic factors ; risk ; survival analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In breast cancer clinical research, an important goal is to analyze how factors are seen to affect the disease process. Meanwhile, the disease progression is not fully modelled using standard analysis since transitions between intermediate events such as local-regional recurrences (LRR) or metachronous contralateral breast cancer (MCBC) are not considered. In the present study, the progression of disease was modelled using a multistate model. By this approach, we assessed transitions during the course of the disease and studied prognostic factors for each transition. The model was applied to 6,185 patients with unilateral ductal invasive breast cancer, clinical stage I through III, treated between 1981 and 1988 at the Curie Institute. At first diagnosis, high clinical stage, high histological grade, positive lymph nodes, and age less than 40 years were associated with increased risks of LRR, metastases, or death. Except age, the same factors remained predictive for metastases or death following LRR. Chemotherapy for the first cancer was associated with a decreased risk for developing MCBC. As the time interval from diagnosis of the primary tumor to that of a local or contralateral recurrence increased, the risk of metastases or death decreased. Nodal status for the first tumor and clinical stage for the contralateral tumor increased the risk of metastases or death following MCBC. Conversely, the risk decreased for patients who received adjuvant hormone therapy following MCBC. In conclusion, the multistate model offers us a much more appropriate way to study prognostic factors for each transition in breast cancer disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006197524405
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  • 79
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    Electronic Resource
    Methodological arguments for the necessity of randomized trials in high-dose chemotherapy for breast cancer (1999)
    Springer
    Breast cancer research and treatment 54 (1999), S. 31-38 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; high-dose chemotherapy ; randomized trials ; stem-cell transplantation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In the past ten years high-dose chemotherapy with autologous haematopoetic stem-cell support (HD-CT) has increasingly been used for breast cancer. But the vast majority of trials are small phase I/II studies showing until now not enough evidence that HD-CT is superior to conventional-dose chemotherapy (CD-CT). In contrast to this, the public perception of this treatment is different. Patients as well as physicians often uncritically believe in reports contrasting the positive results obtained in case series treated by HD-CT with those of historical control groups. This leads to the problem that many patients and also clinicians are not willing to participate in randomized trials on this topic. A critical assessment of current knowledge on the effectiveness of HD-CT in breast cancer is given. The problems related to the use of historical controls, in general, and especially in the setting of HD-CT are demonstrated. Using data of patients treated with CD-CT within trials of the German Breast Cancer Study Group (GBSG) it will be shown that results similarly favorable to those reported from patients treated with a high-dose regimen may be produced using quite simple selection mechanisms. Comparisons of patients treated with HD-CT with historical control groups of patients treated with CD-CT may be misleading. A valid treatment comparison is only possible by means of large randomized trials. Clinicians should participate in the ongoing trials and enter all eligible patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006111821492
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  • 80
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    Electronic Resource
    Reduced telomere DNA content is correlated with genomic instability and metastasis in invasive human breast carcinoma (1999)
    Springer
    Breast cancer research and treatment 54 (1999), S. 59-64 
    Details
    ISSN: 1573-7217
    Keywords: aneuploidy ; breast cancer ; genomic instability ; metastasis ; prognostic markers ; telomeres
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Telomere shortening leads to genomic instability and has been correlated with poor outcome in several types of cancer. A recently described, robust titration assay was used to quantify telomere DNA content in frozen and paraffin-embedded specimens of 49 invasive human breast carcinomas, including tumors with normal or abnormal contents of genomic DNA, which produced regional, distant, or local disease. Telomere DNA contents ranged from 53% to 370% of the content in a reference DNA purified from normal placenta. Tumors were divided into three groups of approximately equal size based on increasing telomere DNA content. All of 16 tumors in the group with the least telomere DNA (Group I), were aneuploid compared to 9/17 tumors in the group with the most telomere DNA (Group III). The Chi-square test for trend indicated that tumors with the least telomere DNA were significantly more likely to be aneuploid than tumors with the most telomere DNA (p〈0.002). Twelve of 14 tumors in Group I also produced metastatic disease compared to 8/15 tumors in Group III. The Fischer Exact Test indicated that tumors with the least telomere DNA were significantly more likely to be metastatic than tumors with the most telomere DNA (p〈0.05). There was no association between telomere DNA content and patients’ age, tumors’ size, grade, stage, or fraction of cells in S-phase. The correlation of reduced telomere DNA content with aneuploidy and metastasis, both of which are associated with poor outcome in invasive breast carcinoma, implies that telomere DNA content also could have prognostic value.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006128228761
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  • 81
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    Electronic Resource
    Applying the Nottingham Prognostic Index to a Swedish breast cancer population (1999)
    Springer
    Breast cancer research and treatment 53 (1999), S. 1-8 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; histopathological grade ; Nottingham Prognostic Index ; prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The aim of this study was to assess the applicability of histopathological grading according to the protocol of Elston/Ellis and the Nottingham Prognostic Index (NPI) to a defined breast cancer population. The NPI is the sum of the individual scores concerning grade, tumour size, and lymph node status, each weighted according to regression coefficients of a Cox proportional hazard analysis and calculated for each individual breast cancer patient. 630 consecutive patients with invasive breast cancer diagnosed 1988–91 were retrospectively followed up and their tumours reviewed and graded. A Cox proportional hazard analysis was performed. Grade, lymph node status, and tumour size were statistically significant predictors of survival within the follow up period (median 7.2 years). Similar to NPI, a temporary index (Kalmar Prognostic Index, KPI) was derived and normalised to NPI for comparison (KPI(norm)). NPI and KPI(norm) gave similar prognostic power in spite of the differences of the patient populations from which the 2 indices were derived. Patients with NPI 4 or less had 0.66% breast cancer specific mortality during the follow up time. 14% of the patients with NPI 4.1–5 and 32% of those with an index sum 5.1–6 died from breast cancer during this time. Younger patients tended to have higher grade tumours. We advocate the common use of grade and the NPI in order to increase the comparability of groups of patients receiving different therapies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006052115874
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  • 82
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    Electronic Resource
    Analyses of microsatellite instability and the transforming growth factor‐β receptor type II gene mutation in sporadic breast cancer and their correlation with clinicopathological features (1999)
    Springer
    Breast cancer research and treatment 53 (1999), S. 33-39 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; microsatellite instability ; TGF‐β RII gene ; clinicopathological features ; prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To determine the incidence of microsatellite instability (MSI) and its relationship with both clinicopathologic parameters and patient survival, 101 cases of breast cancer were investigated. In addition, transforming growth factor‐β (TGF‐β) receptor type II (RII) gene mutation was also examined to clarify the relation to MSI in breast cancer development. MSI and RII gene mutation were screened by single strand conformation polymorphism (SSCP). The mutations of the RII gene were confirmed by a direct sequence. An association between the MSI status and the clinicopathological features was examined to assess the potential of the MSI status as a prognostic indicator in sporadic breast cancer cases. MSI was detected in 12 of 101 (11.9%) breast cancer cases. The positive MSI breast cancer cases showed relatively more advanced disease than negative MSI cases, and also exhibited relatively poorer prognoses. No RII gene mutations were observed in any of the breast cancer cases. Our data suggest that the MSI status may thus be a useful indicator for the prognosis of sporadic breast cancer cases. However, the breast seems to be an infrequent target organ for cancer development through RII gene mutations. As a result, tumor progression through this pathway appears to be related to organ specificity. For positive MSI breast cancers, other target genes therefore still need to be identified.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006167210269
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  • 83
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    Electronic Resource
    Assessment of quality of life in women undergoing hormonal therapy for breast cancer: validation of an endocrine symptom subscale for the FACT‐B (1999)
    Springer
    Breast cancer research and treatment 55 (1999), S. 187-197 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; endocrine therapy ; FACT‐B ; FACT‐ES ; quality of life
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Existing quality of life instruments do not include adequate items to measure the side effects and putative benefits of hormonal treatments given in breast cancer. We report the development and validation of an 18 item endocrine subscale (ES) to accompany a standardised breast cancer quality of life measure, the Functional Assessment of Cancer Therapy (FACT‐B) [1]. The FACT‐ES (FACT‐B plus ES) was tested initially on 268 women with breast cancer receiving endocrine treatments. Alpha coefficients for all subscales demonstrated good internal consistency (range α = 0.65–0.87). Test‐retest reliability of the ES indicated good stability (r = 0.93, p 〈 0.001). Advanced breast cancer patients' quality of life was high, showing the efficacy of endocrine therapy, but women with primary disease reported better physical, social, and functional well‐being and fewer breast cancer concerns. Most frequently reported symptoms were loss of sexual interest (31%), weight gain (25%), and hot flushes (24%). Significant differences were found between treatment groups for hot flushes and vaginal dryness. Two assessments of the instrument's responsiveness to change were made; 32 women in a clinical trial of endocrine therapy and 18 women without breast cancer taking HRT completed the FACT‐ES at baseline, 4, 8, and 12 weeks. Trial patients reported significantly more symptoms at 8 and 12 weeks than at baseline. Women taking HRT reported significantly fewer or less severe symptoms than at baseline. In conclusion the FACT‐ES has acceptable validity and reliability and is sensitive to clinically significant change, making it suitable for clinical trials of endocrine therapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006263818115
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  • 84
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    Electronic Resource
    Insulin‐like growth factor (IGF)‐I rescues breast cancer cells from chemotherapy‐induced cell death – proliferative and anti‐apoptotic effects (1999)
    Springer
    Breast cancer research and treatment 56 (1999), S. 1-10 
    Details
    ISSN: 1573-7217
    Keywords: apoptosis ; breast cancer ; doxorubicin ; IGF‐I ; paclitaxel
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Insulin‐like growth factor (IGF)‐I protects many cell types from apoptosis. As a result, it is possible that IGF‐I‐responsive cancer cells may be resistant to apoptosis‐inducing chemotherapies. Therefore, we examined the effects of IGF‐I on paclitaxel and doxorubicin‐induced apoptosis in the IGF‐I‐responsive breast cancer cell line MCF‐7. Both drugs caused DNA laddering in a dose‐dependent fashion, and IGF‐I reduced the formation of ladders. We next examined the effects of IGF‐I and estradiol on cell survival following drug treatment in monolayer culture. IGF‐I, but not estradiol, increased survival of MCF‐7 cells in the presence of either drug. Cell cycle progression and counting of trypan‐blue stained cells showed that IGF‐I was inducing proliferation in paclitaxel‐treated but not doxorubicin‐treated cells. However, IGF‐I decreased the fraction of apoptotic cells in doxorubicin‐ but not paclitaxel‐treated cells. Recent work has shown that mitogen‐activated protein kinase (MAPK) and phosphotidylinositol‐3 (PI‐3) kinase are activated by IGF‐I in these cells. PI‐3 kinase activation has been linked to anti‐apoptotic functions while MAPK activation is associated with proliferation. We found that IGF‐I rescue of doxorubicin‐induced apoptosis required PI‐3 kinase but not MAPK function, suggesting that IGF‐I inhibited apoptosis. In contrast, IGF‐I rescue of paclitaxel‐induced apoptosis required both PI‐3 kinase and MAPK, suggesting that IGF‐I‐mediated protection was due to enhancement of proliferation. Therefore, IGF‐I attenuated the response of breast cancer cells to doxorubicin and paclitaxel by at least two mechanisms: induction of proliferation and inhibition of apoptosis. Thus, inhibition of IGF‐I action could be a useful adjuvant to cytotoxic chemotherapy in breast cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006208721167
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  • 85
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    Electronic Resource
    Hypermethylation of the Wilms' tumor suppressor gene CpG island in human breast carcinomas (1999)
    Springer
    Breast cancer research and treatment 56 (1999), S. 35-43 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; CpG island ; DNA hypermethylation ; Wilms' tumor suppressor gene
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract CpG island hypermethylation is known to be associated with transcriptional silencing of tumor suppressor genes in neoplasia. We have previously detected aberrantly methylated sites in the first intron of the Wilms' tumor suppressor (WT1) gene in breast cancer. In the present study, we extended the investigation to a CpG island located in the promoter and first exon regions of WT1. Methylation of this CpG island was found to be extensive in MCF‐7 and MDA‐MB‐231 breast cancer cells, as well as in 25% (five of 20 patients) of primary breast tumors. While levels of the known 3.0‐kb WT1 mRNAs were decreased or not detected in these cell lines, the expression could be partially restored following treatment with a demethylation agent, 5‐aza‐2′‐deoxycytidine. Surprisingly, a novel 2.5‐kb WT1 transcript was expressed at high levels in both untreated and treated MDA‐MB‐231 cells. This novel transcript was likely a WT1 variant missing the first exon, and therefore escaped the methylation control present in the normal transcript. Our study implicates the future need to investigate the significance of this aberrant transcript as well as the role of WT1 CpG island hypermethylation in breast neoplasia.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006222803788
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  • 86
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    Electronic Resource
    G1‐S transition defects occur in most breast cancers and predict outcome (1999)
    Springer
    Breast cancer research and treatment 56 (1999), S. 103-110 
    Details
    ISSN: 1573-7217
    Keywords: cell cycle ; cyclins ; p16 ; p27 ; retinoblastoma protein ; breast cancer ; survival
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Cell cycle deregulation is frequently observed in tumors and has moreover been proposed to be a requirement for tumor development. By analyzing the expression of p27 by immunohistochemistry in 100 primary breast tumors and combining the analyses with our earlier characterization of cyclin E, D1, p16, and the retinoblastoma protein (pRB), we have been able to cover the majority of potential G1–S transition defects and observed that 90% of the tumors had alterations in one or several cell cycle regulatory proteins. Considerable variations in protein levels were found among tumors, with low p16 expression as the most common alteration followed by cyclin E or cyclin D1 overexpression, low p27 expression or pRB inactivation in decreasing prevalence. Tumors were grouped according to observed combinations of defects and the proliferative capacity was determined for each group by analyzing Ki–67 labeling index. Low proliferation was observed in tumors with: low p16; high cyclin Dl with normal or high p16 expression; and in tumors without cell cycle defects. Tumors with high cyclin E/low p27 or pRB defects showed higher proliferation. The survival differed noticeably for patients with various combinations of cell cycle defects, and four distinctive clusters were identified showing significantly different breast cancer specific survival (p 〈 0.0001) for both node-positive (p=0.0006) and node-negative patients (p 〈 0.0001). In summary, we have shown that G1-S transition defects are nearly obligatory in breast tumors and that the specific type of cell cycle defect influences the clinical behavior of the tumor.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006208419350
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  • 87
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    Electronic Resource
    Hsp27 overexpression inhibits doxorubicin–induced apoptosis in human breast cancer cells (1999)
    Springer
    Breast cancer research and treatment 56 (1999), S. 185-194 
    Details
    ISSN: 1573-7217
    Keywords: apoptosis ; breast cancer ; doxorubicin ; hsp27 ; topoisomerase II
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Previously we demonstrated that heat shock protein 27 (hsp27) overexpression confers resistance to the chemotherapeutic agent doxorubicin in MDA–MB–231 breast cancer cells. Since induction of apoptosis is one underlying mechanism of chemotherapeutic drug action, we investigated the effect of hsp27 overexpression on doxorubicin–induced apoptosis, finding that hsp27 protects MDA–MB–231 cells from apoptosis. We also examined expression of the doxorubicin target, topoisomerase II (topo II), in control and hsp27–overexpressing stable transfectants, as topo II expression is important for both drug sensitivity and the initiation of apoptosis by doxorubicin. The relative levels of both topo IIα and β were higher in the controls than the hsp27–overexpressing clones, suggesting that the apoptotic protective effect of hsp27 overexpression in MDA–MB–231 cells is associated with altered topo II expression.abstract
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006207009260
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  • 88
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    Electronic Resource
    pS2 (TFF1) levels in human breast cancer tumor samples: correlation with clinical and histological prognostic markers (1999)
    Springer
    Breast cancer research and treatment 56 (1999), S. 251-263 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; mRNA ; pS2 ; prognostic marker ; RT–PCR ; TFF1
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The expression of pS2 (TFF1) has been previously shown to identify patients with improved response to anti–hormonal therapy and more favorable outcome. In the current study, 100 human breast carcinoma samples obtained from the Manitoba Breast Tumor Bank were analyzed for pS2 mRNA using a quantitative, competitive reverse transcriptase–polymerase chain reaction (qcRT–PCR) assay. A pS2/ß–actin cut–off criterion of 0.010 was established to classify tumors as either pS2 positive or pS2 negative. pS2 mRNA levels were positively associated with both ER and PR, with the majority of ER+ (59) and PR+ (60) tumors also being positive for pS2. In addition, a significant linear correlation was observed between the amount of pS2 mRNA and ER (p〈0.0001) and PR (p〈0.0001) protein. pS2 mRNA levels also exhibited an inverse association with tumor size and histological grade, consistent with the observation that pS2 is primarily expressed in small (T 〈 2.0 cm), but well differentiated tumors (Grades I and II). No associations were observed with tumor cell type, patient age, or lymph node status. The strong correlation displayed between pS2 and a number of currently used breast cancer prognostic markers supports the clinical use of pS2 to further assess tumor status and patient outcome.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006215310169
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  • 89
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    Electronic Resource
    Invasion marker PAI‐1 remains a strong prognostic factor after long‐term follow‐up both for primary breast cancer and following first relapse (1999)
    Springer
    Breast cancer research and treatment 54 (1999), S. 147-157 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; cathepsin D ; PAI‐1 ; prognosis ; S‐phase fraction ; uPA
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In 1991, our group was the first to report the prognostic strength of plasminogen activator inhibitor type 1 (PAI‐1) in primary breast cancer. The prognostic impact of invasion markers PAI‐1 and urokinase‐type plasminogen activator (uPA) on disease‐free survival (DFS) and overall survival (OS) in breast cancer has since been independently confirmed. We now report on the prognostic impact of PAI‐1 and uPA after long‐term median follow‐up of 77 months for our cohort (n=316). Levels of uPA, PAI‐1, and cathepsin D were determined in tumor tissue extracts by immunoenzymatic methods. S‐phase fraction (SPF) was measured flowcytometrically in paraffin sections. Using log‐rank statistics, optimized cutoffs were found for PAI‐1 (14 ng/mg), uPA (3 ng/mg), cathepsin D (41 pmol/mg), and SPF (6%). In all patients, various factors (PAI‐1, uPA, nodal status, SPF, cathepsin D, grading, tumor size, hormone receptor status) showed significant univariate impact on DFS. In Cox analysis, only nodal status (p 〈 0.001, RR: 3.1) and PAI‐1 (p 〈 0.001, RR: 2.7) remained significant. In node‐negative patients (n = 147), PAI‐1, uPA, and SPF had significant univariate impact on DFS, whereas in Cox analysis, only PAI‐1 was significant. PAI‐1 was also significant for DFS within subgroups defined by established factors. In CART analysis, uPA enhanced the prognostic value of PAI‐1 and nodal status for determination of a very‐low‐risk subgroup. For OS, only lymph node status and PAI‐1 were significant in multivariate analysis. PAI‐1 levels in the primary tumor were also a significant prognostic marker for survival after first relapse in both univariate and multivariate analysis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006118828278
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  • 90
    Electronic Resource
    Electronic Resource
    Association between endometrial cancer and tamoxifen treatment of breast cancer (1999)
    Springer
    Breast cancer research and treatment 54 (1999), S. 255-260 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; endometrial cancer ; tamoxifen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A retrospective cohort‐study in 4109 breast cancer patients was undertaken to determine how tamoxifen affected the risk of endometrial cancer. Data on 1701 tamoxifen‐treated women were analysed. Two thousand four hundred and eight non‐tamoxifen users served as control group. The occurrence of new primary uterine cancers was assessed by computerized linkage to the Austrian Cancer Registry. Twenty‐five women who subsequently developed endometrial cancer were identified. Eight uterine cancers occurred in the tamoxifen group, whereas 17 uterine cancers were found in the control group. The estimate of the relative risk (RR) showed an increased risk to develop endometrial cancer for the tamoxifen group RR 1.136 (95% CI 0.71; 1.80). Analysis of relevant confounding variables did not show any differences in the two groups. In conclusion, this retrospective study demonstrated a non‐significant increased risk of endometrial cancer in women receiving tamoxifen as treatment for breast cancer. However, the magnitude of RR and the absolute number of endometrial cancer cases in this long term observation demonstrate clearly that the clinical benefit of tamoxifen therapy greatly outweighs the risk.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006126411210
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  • 91
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    Electronic Resource
    Tissue inhibitor of metalloprotease (TIMP)‐1 and proliferative behaviour of clonal breast cancer cells (1999)
    Springer
    Breast cancer research and treatment 54 (1999), S. 235-244 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; cell culture ; cell growth ; TIMP‐1
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In the present paper, we have examined whether human tissue inhibitor of metalloprotease‐1 (hTIMP‐1) is able to exert a growth factor‐like effect on two clonal cell lines (BC‐3A and BC‐61), isolated from a parental line of human breast carcinoma cells (8701‐BC), and endowed with different growth and invasive behaviour ‘in vitro’ and in nude mouse. The data obtained indicate that only the more tumorigenic clonal cell line (BC‐61) is responsive to hTIMP‐1 treatment by increasing its proliferative rate in a dose‐dependent manner. It was also found that BC‐61 cells selectively express a transmembrane protein of about 80 kDa able to bind hTIMP‐1 ‘in vitro’ and ‘in vivo’ with high affinity (Kd of 0.07 ± 0.004   nM), and that treatment of BC‐61 cells with a proliferation‐promoting concentration of hTIMP‐1 is able to stimulate tyrosine‐targeted phosphorylation. The cumulative results obtained strongly support the hypothesis that hTIMP‐1, ‘classically’ regarded as a collagenase inhibitor, may be a crucial element of the extracellular signalling network during breast cancer development by controlling cell growth phenotype in autocrine and paracrine manner, and that intratumoural heterogeneity for the biological response to TIMP‐1 may exist within the composite cell population of the primary tumour site.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006121129382
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  • 92
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    Electronic Resource
    α2‐Adrenergic effect on human breast cancer MCF‐7 cells (1999)
    Springer
    Breast cancer research and treatment 55 (1999), S. 41-49 
    Details
    ISSN: 1573-7217
    Keywords: α2‐adrenergic agonists ; α2‐adrenergic antagonists ; α2‐adrenoceptor ; breast cancer ; catecholamines ; human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract (-)Epinephrine (Epi) and –Norepinephrine (NEpi) significantly stimulated tritiated Thymidine incorporation in MCF‐7 cells at concentrations 10–30 pM to 10 nM, with an EC50 of 10 pM for Epi and 14.2 pM for NEpi. To characterize this action, cells were incubated in the presence of NEpi or Epi and different antagonists. The β‐adrenergic antagonist Propanolol showed no effect on the agonist's stimulation, whereas the α‐adrenergic antagonist Phentolamine, reverted it completely at high concentrations (100 μM). The α1‐adrenergic antagonist Prazosin (Pra) acted only at high concentrations, while the α2‐adrenergic antagonist Yohimbine (Yo) reverted the stimulation at an EC50 of 0.11μM. Likewise, when the cells were incubated in the presence of the specific α2‐adrenergic agonist Clonidine (Clo), Thymidine incorporation was significantly stimulated at an EC50 of 0.298 pM. Again, the incubation of the cells in the presence of the α1‐adrenergic antagonist Pra exerted its action at high concentrations, whereas the α2‐adrenergic antagonist Yo showed a clear reversal of the agonist's enhancement at an EC50 of 0.136 μM. Moreover, Clo caused a clear and significant inhibition of stimulated cAMP levels both in the intracellular and the extracellular fractions. Yo showed a complete reversion of cAMP levels to control values in the presence of Clo, while Pra had the opposite effect. These data suggest that the stimulation provoked in Thymidine incorporation by the agonists Epi, NEpi, and Clo is, at least in part, due to an α2‐adrenergic mechanism directly on tumoral cells, and that the effect is coupled with inhibition of cAMP levels, as described for this kind of receptors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006196308001
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  • 93
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    Differential effects of chemotherapeutic agents on the Bcl‐2/Bax apoptosis pathway in human breast cancer cell line MCF‐7 (1999)
    Springer
    Breast cancer research and treatment 55 (1999), S. 73-83 
    Details
    ISSN: 1573-7217
    Keywords: apoptosis ; Bax ; Bcl‐2 ; breast ; chemotherapy ; estradiol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The present study explored the effects of three commonly used chemotherapeutic agents on the Bcl‐2/Bax apoptosis pathway and the interaction of these chemotherapeutic drugs with the estradiol‐mediated regulation of this pathway. Our results showed that: (1) Treatment of MCF‐7 cells with Adriamycin resulted in time‐ and concentration‐dependent decreases in Bcl‐2 and increases in Bax mRNA and protein levels. (2) Camptothecin elicited similar trends on Bcl‐2 and Bax as Adriamycin, while etoposide, at 50–100 fold (1–5 μM) the effective concentration of Adriamycin and camptothecin, only resulted in an increase in Bax mRNA levels. (3) Adriamycin and camptothecin, but not etoposide, were effective in suppressing estradiol‐stimulated increases in Bcl‐2 mRNA levels. Our study provides evidence that the Bcl‐2/Bax apoptosis pathway may be differentially regulated by chemotherapeutic agents. In addition, interaction between these agents and estradiol on the Bcl‐2/Bax apoptosis pathway may also exist.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006190802590
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  • 94
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    Electronic Resource
    Differentially expressed genes associated with the metastatic phenotype in breast cancer (1999)
    Springer
    Breast cancer research and treatment 55 (1999), S. 125-134 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; differential display ; gene expression ; invasion ; metastasis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We have previously shown that human breast carcinoma cells demonstrating an interconverted phenotype, where keratin (epithelial marker) and vimentin (mesenchymal marker) intermediate filaments are both expressed, have an increased ability to invade a basement membrane matrix in vitro. This increase in invasive potential has been demonstrated in MDA‐MB‐231 cells, which constitutively express keratins and vimentin, and in MCF‐7 cells transfected with the mouse vimentin gene (MoVi). However, vimentin expression alone is not sufficient to confer the complete metastatic phenotype in MoVi cells, as determined by orthotopic administration. Thus, in the present study, differential display analysis was utilized to identify genes that are associated with the invasive and/or metastatic phenotype of several human breast cancer cell lines. Forty‐four of 84 PCR fragments were differentially expressed as assessed by Northern hybridization analysis of RNA isolated from MCF‐7, MoVi, and MB‐231 cell lines. Polyadenylated RNA from a panel of poorly invasive, invasive/non‐metastatic, and invasive/metastatic breast carcinoma cell lines was used to differentiate between cell‐specific gene expression and genes associated with the invasive and/or metastatic phenotype(s). We observed that lysyl oxidase and a zinc finger transcription factor were expressed only in the invasive and/or metastatic cell line; whereas, a thiol‐specific antioxidant and a heterochromatin protein were down‐regulated in these cells. In contrast, tissue factor was expressed only in breast carcinoma cell lines having the highest invasive potential. These results suggest that specific genes involved in breast cancer invasion and metastasis can be separated by differential display methodology to elucidate the molecular basis of tumor cell progression.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006188129423
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  • 95
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    Reduced expression of p27Kip1 protein is associated with poor clinical outcome of breast cancer patients treated with systemic chemotherapy and is linked to cell proliferation and differentiation (1999)
    Springer
    Breast cancer research and treatment 55 (1999), S. 159-165 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; cell cycle ; cyclin‐dependent kinase inhibitor ; differentiation ; p27Kip1 ; prognosis ; proliferation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The cyclin‐dependent kinase inhibitor p27Kip1 is a negative regulator of cell proliferation. Its expression is known to be altered in a proteasome‐dependent manner without changes in DNA level. Reduced expression of p27Kip1 is associated with aggressive behavior in a variety of human cancers. We investigated expression of p27Kip1 protein in human breast cancer using immunohistochemistry to assess its biologic implication along with cell‐cycle analysis by flow cytometry. A total of 68 patients with invasive ductal cancer received adjuvant chemotherapy with cyclophosphamide, methotrexate, and 5‐FU every 3 weeks for six cycles. In epithelial cells of normal and benign breast disease, expression of p27Kip1 was well preserved while its expression markedly decreased in breast cancer (45 of 68). Expression of p27Kip1 is significantly reduced in poorly differentiated cancers and in the advanced stage of the disease. Levels of p27Kip1 expression correlated with cell populations in G0/G1 phase of the cell cycle. In survival analysis, p27Kip1 was useful to predict disease free survival but not overall survival of the patients after adjuvant chemotherapy. In summary, p27Kip1 seems to have a role in the cell proliferation and differentiation process during carcinogenesis of breast cancer. The results of the present study suggest that p27Kip1 can be used in predicting response to systemic chemotherapy in a subset of patients with breast cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006258222233
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  • 96
    Electronic Resource
    Electronic Resource
    Breast cancer and timing of surgery during menstrual cycle: a 5‐year analysis of 248 premenopausal women (1999)
    Springer
    Breast cancer research and treatment 55 (1999), S. 259-266 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; menstrual cycle phase ; premenopausal ; prognosis ; surgery
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In the present report, we retrospectively analyzed the impact of the timing of surgery during menstrual cycle on disease‐free and overall survival of 248 premenopausal patients with stage I/Il breast cancer who underwent surgery followed by anthracycline‐containing adjuvant chemotherapy. With a median follow‐up of 5 years, no statistically significant differences were observed in disease‐free or overall survival between women operated upon during the follicular (days 0–14) and the luteal (days 15–32) phase of the menstrual cycle. The impact on disease‐free and overall survival of lymph‐node status, tumor size and hormone receptor expression, but not of the phase of the menstrual cycle at the time of surgery, was confirmed by univariate and multivariate analysis. However, when combined with hormone receptor status, the phase of the menstrual cycle at the time of surgery proved useful to better define the prognosis of primary breast cancer patients, with significantly longer disease‐free and overall survival for patients operated upon during the follicular phase and with positive hormone receptors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006276120841
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  • 97
    Electronic Resource
    Electronic Resource
    Early age at menopause and breast cancer: are leaner women more protected? A prospective analysis of the Dutch DOM cohort (1999)
    Springer
    Breast cancer research and treatment 55 (1999), S. 285-291 
    Details
    ISSN: 1573-7217
    Keywords: body mass index ; breast cancer ; menopause ; smoking
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To investigate the relationship between age at menopause, body mass index, and breast cancer risk, we used data from a prospective cohort study (DOM cohort) in the Netherlands. Participants in this breast cancer‐screening project included 10,591 women living in Utrecht, aged 49–66 years at enrolment. During a median follow‐up period of 19 years, women attended screening rounds at which anthropometric measurements were taken and questions were asked about menopausal status, age at menopause, medication use and other risk factors for breast cancer. Cox regression analysis was used to investigate the relationship between age at menopause and subsequent breast cancer risk. Breast cancer incidence decreased with an earlier age at menopause. Women with a menopausal age of 44 years or younger had a 34% lower risk of breast cancer, than women with a menopausal age over 54 years (hazard ratio is 0.66 (95% confidence interval 0.43–0.91)). The annual hazard of breast cancer incidence decreased by 2.6% per year reduction in age at menopause. The protective effect of an early age at menopause was stronger for women with a low body mass index (≤27 kg/m2; reduction of 44%) than for women with a high body mass index (〉27 kg/m2; reduction of 24%), although this difference was not statistically significant (P for interaction = 0.58). This difference was most pronounced in women who had ever smoked. Adjustment for known breast cancer risk factors did not alter the crude risk estimates significantly. In conclusion, this study provides evidence of the protective effect of lower age at menopause on subsequent breast cancer risk. This protective effect may be even stronger in leaner women.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006277207963
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  • 98
    Electronic Resource
    Electronic Resource
    Suppression of parathyroid hormone‐related protein messenger RNA expression by medroxyprogesterone acetate in breast cancer tissues (1999)
    Springer
    Breast cancer research and treatment 56 (1999), S. 11-23 
    Details
    ISSN: 1573-7217
    Keywords: androgen receptor ; bone metastasis ; breast cancer ; medroxyprogesterone acetate ; parathyroid hormone‐related protein ; progesterone receptor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The level of parathyroid hormone‐related protein (PTHrP) expressed in breast cancer tissue is closely related to the incidence of bone metastasis. We examined the PTHrP mRNA expression in breast cancer tissues by coamplification polymerase chain reaction (PCR) in mole ratio to internal standard β‐actin mRNA. The PTHrP expression was higher in premenopausal patients than in postmenopausal patients (P〈0.05). More pronounced difference by menopause found in estrogen receptor (ER) positive groups (P〈0.001) indicated that the PTHrP expression in breast cancer tissue is hormonally regulated and might be altered by endocrine agents. To clarify the changes of PTHrP expression by endocrine therapy of breast cancer, we measured PTHrP expression in the breast cancer tissue incubated for 24 h with 1 × 10−8 M of estradiol (E2), 1 × 10−6 M of tamoxifen (TAM) and 1 × 10−5 M of medroxyprogesterone acetate (MPA). The PTHrP expression was decreased significantly by MPA (P〈0.005), while E2 and TAM did not change the PTHrP expression. Progesterone receptor (PgR) mRNA expression was also examined to confirm that the breast cancer tissue responds to E2 and TAM. The results were well compatible with the better therapeutic effect of MPA reported for the treatment of breast cancer with bone metastases. As a potential candidate for the receptor that mediates the suppressive effect of MPA, androgen receptor (AR) is suggested most probable. Present results also demonstrated that the clinical response of individual tumors is closely associated with the early in vitro changes of gene expression detected in the cancer specimen.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006254006088
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  • 99
    Electronic Resource
    Electronic Resource
    Quality of life in the first year after breast cancer surgery: rehabilitation needs and patterns of recovery (1999)
    Springer
    Breast cancer research and treatment 56 (1999), S. 45-57 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; psychological distress ; quality of life ; rehabilitation needs
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background. Although mortality rates from breast cancer are declining, many breast cancer survivors will experience physical and psychological sequelae that affect their everyday lives. Few prospective studies have examined the rehabilitation needs of newly diagnosed breast cancer patients, and little is known about the predictors of health‐related quality of life (QOL) in this population. Methods. Between 1987 and 1990, 227 women with early stage breast cancer participated in a prospective longitudinal study in which detailed information was collected through interviews, standardized measures of QOL and psychological distress, and clinical evaluation. Comparisons of physical and treatment‐related problems were made according to type of surgical treatment. Multivariate regression analysis was performed to examine the predictors of QOL at one year after surgery. Results. Physical and treatment‐related problems were reported frequently one month after breast cancer surgery, and occurred with equal frequency in women receiving modified radical mastectomy or breast conservation treatment. There were no significant differences in problems reported at one year by type of surgery; however, frequently reported problems include ‘numbness in the chest wall or axilla,’ ‘tightness, pulling or stretching in the arm or axilla,’ ‘less energy or fatigue,’ ‘difficulty in sleeping,’ and ‘hot flashes’. There was no relationship between the type of surgery and mood or QOL. Poorer QOL one year after surgery was significantly associated with greater mood disturbance and body image discomfort one month after surgery, as well as positive lymph node involvement. Although the majority of patients experienced substantial disruptions in the physical and psychosocial dimensions of QOL post‐operatively, most women recovered during the year after surgery, with only a minority (〈10%) significantly worsening during that time. Conclusions. At one year after surgery, most women report high levels of functioning and QOL, with no relationship between the type of surgery and QOL. Women who reported lower levels of QOL at one year after diagnosis had greater mood disturbance and poorer body image one month after surgery, as well as lower income and positive axillary nodes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006214830854
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  • 100
    Electronic Resource
    Electronic Resource
    The relation of breast size to breast cancer risk in postmenopausal women (United States) (1999)
    Springer
    Cancer causes & control 10 (1999), S. 115-118 
    Details
    ISSN: 1573-7225
    Keywords: anthropometry ; breast cancer ; breast size ; case-control study ; risk factors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective: Breast size has been hypothesized to predict a woman's risk of breast cancer although studies in the main have not supported an association. In a large, population-based case-control study we examined whether breast size might emerge as a significant risk factor among very lean women in whom breast size might be a truer reflection of the volume of gland mass at risk for malignant change. Methods: The data derive from a population-based case- control study of women aged 50 to 79 years conducted in several New England states and Wisconsin. Incident cases of invasive breast cancer (n=2015) were identified through state tumor registries and controls (n=2556) were selected at random within age strata from population lists. Telephone interviews were conducted to obtain information on known and suspected risk factors which included bra dimensions (cup and back size) prior to a first birth, or at the age of 20 for nulliparous women. Results: We observed a significant positive association for cup size which was limited to women who were the most lean as young adults based on chest circumference. Among those reporting a chest size under 34 inches multivariate-adjusted relative risks were 1.34 (95% CI: 1.04 to 1.74) for cup size B, and 1.76 (95% CI: 1.04 to 3.01) for cup size C and larger, compared to a cup size smaller than B, and the trend for increasing cup size was statistically significant (P=0.005). There was no relation with breast size among women reporting an average or larger back circumference (34 inches or larger). Conclusion: Breast size before a pregnancy is a positive predictor of postmenopausal breast cancer, but this association is limited to those who were especially lean as young women.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008801131831
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