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  • 1995-1999  (836)
  • 1999  (836)
  • General Chemistry  (750)
  • chemotherapy  (86)
  • Atomic, Molecular and Optical Physics
  • Inorganic Chemistry
  • Nuclear reactions
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Material
Years
  • 1995-1999  (836)
Year
Keywords
  • 1
    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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  • 2
    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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  • 3
    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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  • 4
    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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  • 5
    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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  • 6
    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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  • 7
    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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  • 8
    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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  • 9
    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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  • 10
    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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  • 11
    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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  • 12
    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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  • 13
    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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  • 14
    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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  • 15
    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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  • 16
    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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  • 17
    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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  • 18
    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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  • 19
    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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  • 20
    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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  • 21
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008383600448
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  • 22
    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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  • 23
    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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  • 24
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1015052520467
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  • 25
    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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  • 26
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008365511961
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  • 27
    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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  • 28
    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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  • 29
    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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  • 30
    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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  • 31
    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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  • 32
    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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  • 33
    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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  • 34
    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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  • 35
    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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  • 36
    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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  • 37
    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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  • 38
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008361708844
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  • 39
    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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  • 40
    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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  • 41
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008323604269
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  • 42
    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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  • 43
    Electronic Resource
    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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  • 44
    Electronic Resource
    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.
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    URL: http://dx.doi.org/10.1023/A:1008331511578
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  • 45
    Electronic Resource
    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.
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    URL: http://dx.doi.org/10.1023/A:1008364601010
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  • 46
    Electronic Resource
    Electronic Resource
    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.
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    URL: http://dx.doi.org/10.1023/A:1006190802590
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  • 47
    Electronic Resource
    Electronic Resource
    Maintenance treatment with medroxyprogesterone acetate in patients with advanced breast cancer responding to chemotherapy: results of a randomized trial (1999)
    Springer
    Breast cancer research and treatment 55 (1999), S. 51-59 
    Details
    ISSN: 1573-7217
    Keywords: chemotherapy ; endocrine maintenance therapy ; medroxyprogesterone acetate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The purpose of this randomized phase III trial was to study whether medroxyprogesterone acetate (MPA) maintenance treatment prolongs the time to progression in advanced breast cancer patients responding to an induction chemotherapy. Patients with progressive advanced breast cancer previously untreated with anthracylines and progestins were given epirubicin (30 mg/m2) and ifosfamide (2 g/m2) on days 1 and 8 at 3‐weekly intervals. Patients without disease progression after 6 cycles of chemotherapy were randomly assigned to receive, until progression, either no treatment or MPA at a daily total dose of 500 mg. Ninety patients were randomized: 46 to the MPA arm and 44 to the observation arm. Median time to progression was longer in the MPA arm: 4.9 months versus 3.7 months in the intent‐to‐treat analysis (p=0.02), and 4.9 months versus 3.0 months in the secondary efficacy analysis (p=0.012). Seven patients were removed from MPA due to side effects. The changes in patient‐rated quality of life scores were similar in both groups. The median length of survival from randomization was 17.4 months for patients receiving MPA and 18.3 months for patients randomized to observation (p=0.39). In conclusion, in patients with advanced breast cancer achieving remission or non‐progression with 6 cycles of epirubicin and ifosfamide chemotherapy, MPA maintenance treatment led to a significant, though modest, prolongation of the time to progression without affecting overall survival of the study patients.
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    URL: http://dx.doi.org/10.1023/A:1006169012544
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  • 48
    Electronic Resource
    Electronic Resource
    Treatment of advanced breast cancer with gemcitabine and vinorelbine plus human granulocyte colony‐stimulating factor (1999)
    Springer
    Breast cancer research and treatment 55 (1999), S. 203-211 
    Details
    ISSN: 1573-7217
    Keywords: advanced breast cancer ; chemotherapy ; gemcitabine ; vinorelbine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose. A phase II trial was performed to investigate the efficacy and tolerance of gemcitabine, vinorelbine, and recombinant human granulocyte colony‐stimulating factor (G‐CSF) in advanced breast cancer. Patients and methods. Between April 96 and August 97, 60 patients entered this trial. Forty‐five patients were previously untreated and 15 patients had failed previous palliative chemotherapy with (n = 10) or without anthracyclines (n = 5). Therapy consisted of gemcitabine 1000 mg/m2 on days 1 + 15 + 21 and vinorelbine 40 mg/m2 on days 1 + 21, both diluted in 250 ml saline and infused over 30 min. G‐CSF was administered at 5 μg/kg/day subcutaneously from days 2–6 and 22–26. Courses were repeated every 5 weeks. Treatment was continued in case of response or stable disease until a total of six courses. Results. The overall response rate was 55.5% for patients who had not received prior palliative chemotherapy (95% confidence interval, 40%–70.3%), including 5 CR (11.1%) and 20 PR (44.4%) 12 patients (27%) had stable disease (SD), and 8 (18%) progressed. Second‐line treatment with this regimen resulted in 6/15 (40%) objective remissions, 5 had SD, and 4 PD. The median time to progression was 9.5 months (range, 1.5–28) in previously untreated patients, and 7.0 months (range, 2–23) in those who had failed prior chemotherapy. After a median follow‐up time of 15 months, 44 patients (73%) are still alive with metastatic disease. Myelosuppression was commonly observed, though WHO 3 and 4 neutropenia occured in only 9 (l5%) and 2 patients (3%), and was never complicated by septicaemia; grade 3 anemia was noted in 2 patients. Severe (WHO grade 3) nonhematologic toxicity was rarely observed, and included nausea/emesis in 3 and constipation in 2 patients. Conclusions. Our data suggest that gemcitabine and vinorelbine plus G‐CSF is an effective and tolerable first‐ as well as second‐line combination regimen for treatment of advanced breast cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006136112585
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  • 49
    Electronic Resource
    Electronic Resource
    5‐HT3 antiemetic therapy for patients with breast cancer (1999)
    Springer
    Breast cancer research and treatment 57 (1999), S. 207-214 
    Details
    ISSN: 1573-7217
    Keywords: antiemetic therapy ; breast cancer ; chemotherapy ; granisetron ; ondansetron ; quality of life
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Antiemetic treatment should be considered for breast cancer patients receiving moderately emetogenic chemotherapy. Although the extent of chemotherapy‐induced emesis is largely dependent on the emetogenic potential of the specific agents employed, patient characteristics such as age and sex also contribute. Recent clinical studies show that treatment with the currently available 5‐HT3 antagonists effectively reduces the incidence of chemotherapy‐induced nausea and vomiting and improves quality of life in a substantial number of these patients. A Medline search from 1994 through February 1998 identified clinical trials that included previously untreated breast cancer patients using antiemetic therapy such as granisetron, ondansetron, dolasetron, and metoclopramide. The studies reviewed here indicate that the antiemetic efficacy of 5‐HT3 antagonists is equivalent in previously untreated patients receiving moderately emetogenic chemotherapy for breast cancer, depending on the doses and schedules utilized. In particular, two comparative studies of granisetron and ondansetron with specific data for breast cancer patients showed that both agents eliminate nausea in approximately 50%, and vomiting in 60–70% of these patients, with the higher values observed when steroids were added to the 5‐HT3 receptor antagonist regimen. Although the chemotherapy regimens employed for breast cancer are considered only moderately emetogenic, these regimens account for 60–90% of patients experiencing nausea and vomiting. The most recent clinical studies demonstrate that 5‐HT3 antagonists can significantly reduce the incidence of nausea in breast cancer patients receiving moderately emetogenic chemotherapy and should be employed in this setting.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006233802863
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  • 50
    Electronic Resource
    Electronic Resource
    Changes in body composition during breast cancer chemotherapy with the CMF‐regimen (1999)
    Springer
    Breast cancer research and treatment 57 (1999), S. 285-290 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; chemotherapy ; CMF ; weight gain
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Weight gain is a reported problem associated with adjuvant chemotherapy for breast cancer and often generates psychosocial stress in women [1]. It also may affect prognosis and survival. Changes in body composition and weight during chemotherapy, particularly adjuvant treatment of breast carcinoma, have been previously reported [1–3]. Multiple reasons for this weight gain have been suggested though few theories have been scientifically validated [4]. The aim of this study was to investigate body composition and its relationship to weight change associated with the CMF‐based breast cancer chemotherapy protocols. Total body nitrogen (TBN), body fat, total body water (TBW), and anthropometric measurements were conducted on 25 female out‐patients (median age 47, range 26–70 years) receiving adjuvant CMF‐based chemotherapy for breast cancer. Total body nitrogen was measured using the In Vivo Neutron Capture Analysis (IVNCA) technique (on day 1 of cycles 2–6) and TBP was calculated by multiplying TBN by 6.25 [5]. Nitrogen Index (NI) was calculated by expressing TBN as a percentage of normal. There was a significant increase in mean body weight during chemotherapy of 2.35 kg (p〈0.0001). Serial measurements showed no significant change in mean TBN, NI, or percentage body fat. Break down of body weight showed a significant increase in mean TBW of 0.79 kg (p=0.003) and mean fat mass of 1.49 kg (p=0.008). We conclude that weight gain observed during adjuvant chemotherapy for breast carcinoma is primarily due to an increase in fat and TBW.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006220510597
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  • 51
    Electronic Resource
    Electronic Resource
    Niacin deficiency increases the sensitivity of rats to the short and long term effects of ethylnitrosourea treatment (1999)
    Springer
    Molecular and cellular biochemistry 193 (1999), S. 83-87 
    Details
    ISSN: 1573-4919
    Keywords: nitrosourea ; chemotherapy ; anemia ; leukopenia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Most chemotherapy agents function by causing damage to the DNA of rapidly dividing cells, such as those in the bone marrow, leading to anemia and leukopenia during chemotherapy and the development of secondary leukemias in the years following recovery from the original disease. We created an animal model of nitrosourea-based chemotherapy using ethylnitrosourea (ENU) to investigate the effect of niacin deficiency on the side effects of chemotherapy. Weanling Long-Evans rats were fed diets containing various levels of niacin for a period of 4 weeks. ENU treatment started after 1 week of feeding and consisted of 12 doses delivered by gavage, every other day. Cancer incidence was also monitored in the following months. ENU treatment caused many of the acute symptoms seen in human chemotherapy patients, including anemia and neutropenia. Niacin deficiency (ND) had several interesting effects, alone and in combination with ENU. Niacin deficiency alone caused a modest anemia, while in combination with ENU it induced a severe anemia. Niacin deficiency alone caused a 4-fold increase in circulating neutrophil numbers, and this population was drastically reduced by ENU-treatment. In the long term, macin deficiency caused an increased incidence of cancer, especially chronic granulocytic leukemias.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006964227277
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  • 52
    Electronic Resource
    Electronic Resource
    Role of an Anti-epidermal Growth Factor Receptor in Treating Cancer (1999)
    Springer
    Cancer and metastasis reviews 18 (1999), S. 427-436 
    Details
    ISSN: 1573-7233
    Keywords: EGF ; receptor ; monoclonal antibodies ; cancer ; chemotherapy ; radiation therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Recent technological advances, together with the discovery of the important role many growth factors play in modulating cell proliferation and differentiation, have led to the development of novel therapeutic agents for the treatment of cancer. In particular, advances in hybridoma technology and molecular engineering have permitted the development of humanized or chimeric monoclonal antibodies capable of interfering with growth factor signaling pathways. One promising target of interest is the epidermal growth factor receptor (EGFr), which is activated by the ligands EGF and TGF-α. This ligand receptor interaction plays a crucial role in the growth and survival of many human cancers. A chimeric (human/mouse) monoclonal antibody cetuximab (IMC-C225) targets the EGFr and has potential clinical value as an anticancer agent.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006302101468
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  • 53
    Electronic Resource
    Electronic Resource
    Relationship Between Drug Delivery and the Intra-arterial Infusion Rate of SarCNU in C6 Rat Brain Tumor Model (1999)
    Springer
    Journal of neuro-oncology 41 (1999), S. 235-246 
    Details
    ISSN: 1573-7373
    Keywords: brain tumor ; intra-arterial administration ; chemotherapy ; drug delivery ; drug streaming
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The influences of the flow rate on the concentration and distribution of drug in the rat brains and brain tumors after intra-arterial (intra-carotid) administration of [3H]SarCNU (sarcosinamide chloroethyl-1-nitrosourea) were examined. Results obtained at three flow rates via intra-carotid route were compared to those obtained with intravenous administrations. Adult female Wistar rats bearing C6 brain tumor were randomized into four-groups. Groups 1 (G.1) to 3 (G.3) received intra-arterial injection and Group 4 (G.4) received intravenous administration of [3H]SarCNU. G.1 (slow infusion rate) was administered 1 ml of [3H]SarCNU solution over 60 min (0.017 ml/min), Group 2 (G.2; medium infusion rate): 0.2 ml over 5 min (0.04 ml/min), G.3 (fast infusion rate): 1 ml over 5 min (0.2 ml/min), and G.4 (intravenous infusion): 1 ml intravenously over 5 min. Quantitative autoradiographic method was used to measure the concentration and the distribution of [3H]SarCNU in the brain and the brain tumors. The tissue uptake constant of SarCNU in both viable (tumor tissue excluding necrosis) and peak regions (the area of tumor containing top 20% of the tracer concentration) of the intra-arterial injection groups were significantly higher (p〈0.0001) than those in the intravenous group. The mean concentrations of the viable tumor in the intra-arterial groups were 2.92 (G.1), 16.06 (G.2), and 20.8 (G.3) times higher than those of intravenous group. Between the intra-arterial groups, the mean concentration in the viable tumors of G.1 (slow flow rate) was significantly (p〈0.0001) lower than in G.2 and G.3. However, there was no significant difference between G.2 and G.3. In three intra-arterial groups the mean concentration delivery ratios of the brain tumors were high and ranged from 3.07 (G.3) to 3.87 (G.2), but there was no significant difference between them. Only G.4, intravenous group, showed significantly (p〈0.005) lower concentration delivery ratio, 1.26. These results suggest that higher infusion rate in the intra-arterial chemotherapy could have an effect not only on the streaming phenomenon which results in the brain toxicities, but also on the increase in the concentration and the sufficient distribution of a drug in tumors. By finding chemotherapeutic agents to which tumors show high sensitivity and using intra-arterial administration of these agents at more effective flow rate, better clinical results could be achieved in the treatment of patients with malignant brain tumors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006104220315
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  • 54
    Electronic Resource
    Electronic Resource
    Combined Treatment Modality for Anaplastic Oligodendroglioma: A Phase II Study (1999)
    Springer
    Journal of neuro-oncology 43 (1999), S. 179-185 
    Details
    ISSN: 1573-7373
    Keywords: anaplastic oligodendroglioma ; surgery ; radiotherapy ; chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: To investigate feasibility, toxicity and antitumor activity of combined surgery, postoperative radiation therapy (RT) and adjuvant chemotherapy (CHT) in adult patients with pure anaplastic oligodendroglioma (PAO) or mixed anaplastic oligoastrocytoma (MAO). Methods: Between January 1988, and June 1993, 23 patients entered into a phase II study. After surgery, post-operative RT was administered with 60 Gy in 30 daily fractions in 30 treatment days in 6 weeks. Two weeks after RT, adjuvant ‘modified’ PCV (mPCV) (Procarbazine, 60 mg/m2, days 1–14; CCNU, 100 mg/m2, day 1; and vincristine, 1.4 mg/m2 (max. 2 mg), days 1 and 8) was administered every six weeks up to six cycles or until progression occurred. Results: Median survival time is not attained yet, while 1–5 year survival rates are 100%, 100%, 78%, 61%, and 52%, respectively. Median time to tumor progression is not attained yet, while 1–5 year progression-free survival rates are 100%, 100%, 70%, 52%, and 52%, respectively. On univariate analysis of potential prognostic factors, sex, tumor location (frontal versus other), and histology (pure versus mixed anaplastic oligodendroglioma) were not found to influence survival. Age of 〈50 years carried improved prognosis as well as Karnofsky performance status (KPS) 90–100 when compared to KPS of 70–80. Patients having tumors ≤4 cm did better than those with tumors 〉4 cm as well as those with total tumor resection when compared to those with subtotal tumor resection or biopsy only. Acute high-grade (≥3) CHT-related toxicity was mainly hematological with only 3 (13%) patients experiencing acute grade 4 toxicity. Conclusions: Combined treatment modality consisting of surgery, postoperative high-dose RT and mPCV chemotherapy for patients with anaplastic oligodendroglioma was effective with acceptable toxicity. Further studies are needed with more patients and longer follow-up to verify these results in this rare disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006206800947
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  • 55
    Electronic Resource
    Electronic Resource
    Chemotherapy for Advanced CNS Ependymoma (1999)
    Springer
    Journal of neuro-oncology 45 (1999), S. 61-67 
    Details
    ISSN: 1573-7373
    Keywords: ependymoma ; chemotherapy ; CNS ; advanced
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background. The role of chemotherapy in recurrent ependymoma is poorly defined. This study was performed to help clarify the benefits of chemotherapy in this setting. Patients and methods. We retrospectively reviewed the charts of patients with advanced ependymoma of the CNS who received chemotherapy in our institution between 1974 and 1993, inclusive. Sixteen consecutive patients were treated with regimens containing either nitrosourea, platinum, or other combinations exclusive of nitrosourea or platinum. No patient received nitrosourea and platinum concurrently. Two methods were used to define response. The first was a direct comparison of radiographic images before and after chemotherapy more than one month apart. A second broader definition of response that employed four other criteria in addition to imaging studies (symptoms, signs, performance status, and neurologic functional status) was also used. Results. Results were as follows (response rate by imaging studies followed by response rate by scoring in parenthesis): Platinum-based chemotherapy resulted in a 67% (83%) response rate with 33% (0%) remaining stable. Nitrosourea-based regimens resulted in a 25% (60%) response rate with 50% (10%) remaining stable. When combinations other than platinum or nitrosourea were used, 11% (22%) responded and 56% (44%) remained stable. Relative differences in response rates between chemotherapy regimens persisted when the data were analyzed by grade. Median time to progression was 6, 10, and 3 months, respectively. Conclusion. Platinum-based chemotherapy regimens appear to result in higher response rates with lower rates of progression than nitrosourea-based regimens. Other regimens that do not include cisplatinum or nitrosourea appear to be even less effective.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006394407245
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  • 56
    Electronic Resource
    Electronic Resource
    Gossypol Treatment of Recurrent Adult Malignant Gliomas (1999)
    Springer
    Journal of neuro-oncology 43 (1999), S. 79-86 
    Details
    ISSN: 1573-7373
    Keywords: malignant glioma ; gossypol ; lactate dehydrogenase isoenzymes ; chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Gossypol, a polyphenolic compound which depletes cellular energy by inhibition of several intracellular dehydrogenases, has been shown to have antiproliferative activity against human glial tumor cell lines in vitro and in nude mouse xenografts. Human trials of gossypol as a male contraceptive have demonstrated safety of long-term administration. We studied the activity of Gossypol 10 mg PO bid in 27 patients with pathologically confirmed glial tumors which had recurred after radiation therapy. Fifteen patients had glioblastoma, 11 patients anaplastic astrocytoma, 1 patient relapsed low grade glioma. Response was assessed every 8 weeks using CT/MRI scan and clinical criteria including decadron requirement. Treatment was continued until disease progression. Two patients had partial response (PR); 4 had stable disease for 8 weeks or more. One patient maintained a PR with improved KPS for 78 weeks. The other had a PR lasting 8 weeks. Toxicity was mild: 2 heavily pretreated patients had mild thrombocytopenia, 5 patients developed hypokalemia, 3 patients developed grade 2 hepatic toxicity and peripheral edema. Gossypol levels measured by HPLC did not correlate with response or toxicity in this study. We conclude that gossypol is well tolerated and has a low, but measurable, response rate in a heavily pretreated, poor-prognosis group of patients with recurrent glioma. The presumed novel mechanism of action, lack of significant myelosuppression, and activity in patients with advance glioma support further study of gossypol as an antineoplastic agent.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006267902186
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  • 57
    Electronic Resource
    Electronic Resource
    Treatment of Malignant Gliomas in the Elderly (1999)
    Springer
    Journal of neuro-oncology 43 (1999), S. 187-193 
    Details
    ISSN: 1573-7373
    Keywords: malignant gliomas ; elderly ; radiotherapy ; chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The benefit of standard treatment of malignant glioma in older patients is debated. In order to assess the effect of a combination of surgery, radiotherapy and chemotherapy on survival of elderly patients with high grade gliomas, 30 consecutive patients older than 70 years with malignant supratentorial gliomas were studied between 9/93 and 9/96. Median age was 73 years (70–79). The mean Karnofsky performance status (KPS) was 66 (30–100). Patients underwent maximum possible surgery, followed by a course of radiotherapy (45 Gy/25 fractions/5 weeks) with 3 or 4 orthogonal beams and a 2 cm margin around the tumor bed. The administration of chemotherapy was left at the discretion of the responsible physician and 12 patients received reduced dose nitrosourea-based chemotherapy. The overall median survival was 36 weeks. The median time to progression was 26 weeks. Three months after surgery, 26 patients were alive, 5 were in complete response, 2 in partial response and 10 were stabilized. Pre-radiotherapy KPS was the only significant prognostic factor with a median survival of 40 weeks in patients with KPS ≥70 and 25 weeks when KPS was 〉70 (logrank test, p=0.05). In responding and stable patients (57% of the group) the median KPS was 68 and 66 at 1 and 3 months after the completion of radiotherapy. There was no case of radiotherapy-induced dementia with this regimen. Four out of 12 patients who received chemotherapy, experienced WHO grade 3/4 hematotoxicity. This study suggest that some patients older than 70 years with KPS ≥70 may benefit from the treatment of malignant gliomas with surgery followed by reduced dose of limited field radiotherapy. Further studies are needed to define the most appropriate dose of radiotherapy and to evaluate further the risk/benefit ratio of a reduced dose chemotherapy in this population.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006262918694
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  • 58
    Electronic Resource
    Electronic Resource
    Ongoing Protocols for Non-AIDS Primary Central Nervous System Lymphoma (1999)
    Springer
    Journal of neuro-oncology 43 (1999), S. 287-291 
    Details
    ISSN: 1573-7373
    Keywords: primary central nervous system lymphoma ; chemotherapy ; radiotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The optimal treatment for primary central nervous system lymphoma (PCNSL) remains undefined. In this paper, we review the main multi-institutional ongoing protocols for PCNSL. Most of the current protocols evaluate the efficacy of combination high-dose methotrexate-based chemotherapy and brain irradiation in phase II studies. Some trials focus on chemotherapy alone as initial treatment, in order to minimize long-term cognitive sequellae. Because old age appears as a major predisposing factor for combined RT and CT neurotoxicity some specific protocols have been proposed to this particular population.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006266821574
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  • 59
    Electronic Resource
    Electronic Resource
    Phase II Study of Weekly Dose-intensified Cisplatin Chemotherapy with Oral Etoposide in Recurrent Glioma (1999)
    Springer
    Journal of neuro-oncology 44 (1999), S. 59-64 
    Details
    ISSN: 1573-7373
    Keywords: recurrent ; glioma ; astrocytoma ; chemotherapy ; cisplatin ; etoposide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background. In most patients with recurrent glioma chemotherapy is the only remaining treatment option. In general results of chemotherapy in these patients are poor, and trials on new regimens are indicated. Because relatively good results have been achieved with combinations of platin compounds and etoposide, we investigated a dose-intensified cisplatin regimen with oral etoposide. Methods. Eligible patients, with recurrent glioma after surgery and radiation therapy were treated with two four week-cycles with cisplatin 70 mg/m2 on days 1, 8 and 15, combined with oral etoposide 50 mg daily on days 1–15. In responding or stabilized patients, treatment was continued with six four week-cycles of oral etoposide 50 mg/m2 on days 1–21. Toxicity was assessed using the NCI Common Toxicity Criteria, a 50% decrease in contrast enhancing area on MRI scan was considered a partial response. Time to progression was measured from the start of chemotherapy. Results. Sixteen patients were included, 11 were progressive during or immediately after the induction cycles. Two patients achieved a partial response with a time to progression of 42 and 58 weeks. Three patients were stable for 11, 14 and 15 weeks respectively. Toxicity was modest. Discussion. This dose-intensified cisplatin regimen did not result in a significant number of objective responses and even the number of ‘stable disease’ was small. Given the low response rate of this intensive treatment, we consider this intensive regimen inappropriate for these patients.
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    URL: http://dx.doi.org/10.1023/A:1006201909435
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  • 60
    Electronic Resource
    Electronic Resource
    Treatment of Meningeal Gliomatosis (1999)
    Springer
    Journal of neuro-oncology 44 (1999), S. 163-168 
    Details
    ISSN: 1573-7373
    Keywords: meningeal neoplasm ; glioma ; meningeal gliomatosis ; chemotherapy ; radiation therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To evaluate whether vigorous treatment is beneficial for patients with meningeal gliomatosis (MG) we reviewed the case records of 20 consecutive patients treated for a symptomatic MG in our center. All received systemic or intrathecal chemotherapy and six received additional cranial or spinal radiotherapy. Six patients (30%) achieved a partial response (one low-grade astrocytoma, two anaplastic astrocytomas, one anaplastic oligodendroglioma and two glioblastomas). In these cases, clinical improvement was associated with radiological improvement on CT scan or MRI in five and with a major cerebrospinal fluid improvement in three. Three patients (15%) were stable for 3 months or more and 11 (55%) had progressive disease. Median survival was longer for the responding patients (10 months) than for the other patients (2 months). This study suggests that some patients with MG may benefit from a treatment combining radiotherapy to symptomatic areas and chemotherapy with agents that cross the blood–brain barrier or are delivered directly into the CSF.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006399804896
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  • 61
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    Electronic Resource
    Salvage Radiation Therapy for Intracranial Germinoma Recurring After Primary Chemotherapy (1999)
    Springer
    Journal of neuro-oncology 44 (1999), S. 181-185 
    Details
    ISSN: 1573-7373
    Keywords: brain neoplasm ; germinoma ; CNS ; recurrence ; radiotherapy ; chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Systemic chemotherapy has been increasingly used in the primary treatment of intracranial germinoma. However, the recurrence rate seems to be very high after treatment with chemotherapy alone. We used radiation to treat 5 patients harboring intracranial germinoma that recurred following primary chemotherapy. They had received systemic chemotherapy (4 with cisplatin plus etoposide and 1 with adriamycin, vincristine, cyclophosphamide, prednisolone, and cisplatin) 7–24 months before referral. All patients were treated with conventional radiotherapy directed to the primary tumor site or the craniospinal axis with a dose to the primary site ranging from 39.6 to 47.0 Gy (mean, 42.6 Gy). Response to radiation of all the recurrent tumors was good and all tumors disappeared on diagnostic imaging below the dose of 24 Gy. All patients are alive without further recurrence at 61–129 months after salvage radiotherapy. Germinomas recurring after primary chemotherapy do not seem to have acquired cross resistance to radiotherapy. They can usually be cured by standard radiation therapy with 40–47 Gy.
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    URL: http://dx.doi.org/10.1023/A:1006367316168
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  • 62
    Electronic Resource
    Electronic Resource
    Radiation and Concomitant Weekly Administration of Paclitaxel in Patients with Glioblastoma Multiforme. A Phase II Study (1999)
    Springer
    Journal of neuro-oncology 45 (1999), S. 159-165 
    Details
    ISSN: 1573-7373
    Keywords: radiotherapy ; chemotherapy ; paclitaxel ; brain tumors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The present study was conducted to evaluate the activity and toxicity profile of radiation (RT) and concomitant chemotherapy in patients with glioblastoma multiforme (GBM). Thirty-nine patients were treated postoperatively with RT and concomitant administration of paclitaxel. Cranial irradiation was initiated 2–3 weeks postoperatively and was administered in 2.0 fractions, one fraction per day, for 5 consecutive days per week, to a total of 60 Gy. Paclitaxel was delivered at a dose of 100 mg/m2 over 3-h once weekly for 6 weeks. Thirty-three patients received all 6 cycles of paclitaxel according to the protocol. Totally, 217 cycles were delivered all of them at full dose. The median relative dose intensity of paclitaxel was 1 (range 0.88–1.1). Three (7.5%) patients achieved complete and 9 (23%) partial response, while 12 (30.5%) patients demonstrated stabilization of the disease. Side effects from combined chemoradiotherapy were mainly mild. Grade III toxicity included infection (7.5%) and alopecia (5%). Median time to progression was 6 (range 0.9–27) months and median survival 10.7 (range 0.9–39.5+) months. The present study has clearly shown that 100 mg/m2 of paclitaxel in 1-h infusion weekly can be safely given concomitantly with RT in patients with GBM with manageable toxicity. However, the efficacy of this combined modality treatment does not appear to be superior to that of RT alone.
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    URL: http://dx.doi.org/10.1023/A:1006386114104
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  • 63
    Electronic Resource
    Electronic Resource
    Treatment of Supratentorial Glioblastoma Multiforme with Radiotherapy and a Combination of BCNU and Tamoxifen: A Phase II Study (1999)
    Springer
    Journal of neuro-oncology 45 (1999), S. 229-235 
    Details
    ISSN: 1573-7373
    Keywords: BCNU ; tamoxifen ; chemotherapy ; glioblastomas
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract From May 1990 to November 1994, 70 consecutive patients suffering from glioblastoma multiforme were treated following surgery with conventional radiotherapy and adjuvant IV BCNU administered alone or in combination with tamoxifen. Twenty-five patients received BCNU alone (control group A) while 24 patients also received 40 mg of tamoxifen (TMX) PO daily (group B) and 21 received 100 mg of TMX PO daily (group C). There were no significant differences between the 3 groups concerning age, type of resection and median post-operative Karnofsky performance status (KPS). Blood toxicity over grade II occurred in 33.5% of patients receiving TMX versus 12% of patients treated with BCNU alone (p〈0.05). Deep venous thrombosis complications were observed in 4 patients of each TMX group, whereas they were not observed in the control group (p〈0.04). Median time to tumor progression (MTTP) was 35 weeks in the control group and 27 weeks in both TMX groups B and C. Median survival time (MST) was 56, 66 and 51 weeks, respectively. These results suggest that the addition of TMX to standard treatment of glioblastomas does not affect the time to tumor progression and overall survival but may increase the risk of deep venous thrombosis or nitrosourea-induced blood toxicity.
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    URL: http://dx.doi.org/10.1023/A:1006390414555
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  • 64
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    Nucleophilic Aromatic Substitution of Hydrogen in the Reaction of tert-Alkylamines with Nitrosobenzenes - Synthesis and NMR Study of N-(tert-Alkyl)-ortho-nitrosoanilines (1999)
    Weinheim : Wiley-Blackwell
    Liebigs Annalen 1999 (1999), S. 29-35 
    Details
    ISSN: 1434-193X
    Keywords: Nitrosobenzenes ; ortho-Nitrosoanilines ; 2-Nitroso-1,3-phenylenediamines ; Nucleophilic aromatic substitution ; Oxidative nucleophilic substitution of hydrogen ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: -The reaction of primary amines bearing tertiary alkyl groups (e.g. R-NH2; R = tBu, 1-adamantyl) with nitrosobenzenes has been found to proceed by oxidative nucleophilic aromatic substitution of hydrogen, thereby affording N-(tert-alkyl)-ortho- and -para-nitrosoanilines. The replacement of hydrogen proceeds more rapidly than the replacement of ortho- or para-nitro or -bromo substituents. With p-nitronitrosobenzene, both ortho-hydrogen atoms are substituted to afford N,N′-di(tert-alkyl)-4-nitro-2-nitroso-1,3-phenylenediamines 8a,b. The addition of oxidizing agents (e.g. MnO2) increases the yield of products. 1H-, 13C-, 14N- and 15N-NMR studies have confirmed the structures of the compounds under investigation. In ortho-nitrosoanilines, the rotamer with the nitroso group syn to the amino group is favored.
    Additional Material: 3 Tab.
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  • 65
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    Photochemistry of 9,10-Dicarbonyl-9,10-dihydroanthracene - A Source of 9,10-Dehydroanthracene? (1999)
    Weinheim : Wiley-Blackwell
    Liebigs Annalen 1999 (1999), S. 57-60 
    Details
    ISSN: 1434-193X
    Keywords: Benzyne ; Dehydroanthracene ; Matrix isolation ; Photochemistry ; Bergman reaction ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: -9,10-Didehydroanthracene (1) is an interesting derivative of p-benzyne that has been subject of several studies. In contrast to an earlier report, the photochemical decarbonylation of 9,10-dicarbonyl-9,10-dihydroanthracene (2) does not lead to 1 but rather to the ring-opened ene-diyne 4. The key intermediate for this reaction is keto carbene 7 which is formed by monodecarbonylation of 2. Carbene 7 is labile towards visible-light irradiation and easily looses the second CO molecule to give 4. Carbene 7 and diyne 4 are characterized by IR and UV/Vis spectra, the IR spectra are compared to calculations at the B3LYP/6-31G(d,p) level of theory.
    Additional Material: 2 Ill.
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  • 66
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    Reversal Diastereofacial Selectivity in the n-Butyllithium Addition to O-Protected N-Trimethylsilylimines of (2S)-Lactal: Enthalpic versus Entropic Contributions (1999)
    Weinheim : Wiley-Blackwell
    Liebigs Annalen 1999 (1999), S. 61-65 
    Details
    ISSN: 1434-193X
    Keywords: Nucleophilic addition ; Solvent effect ; Reversal of diastereoselectivity ; Temperature effect ; Imines ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: -Commonly observed, but rarely explored, is the possibility of modifying the diastereomeric excess (de%) by means of temperature. A complete reversal in the diastereofacial selectivity could be obtained whenever the diastereoisomers concerned are differentially favored by enthalpy and entropy. The enthalpic or entropic dominance of a diastereoisomer depends greatly on the reaction solvent used.
    Additional Material: 1 Ill.
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  • 67
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    Syntheses of Donor-Acceptor-Substituted 2,6-Stellanes (1999)
    Weinheim : Wiley-Blackwell
    Liebigs Annalen 1999 (1999), S. 73-81 
    Details
    ISSN: 1434-193X
    Keywords: Donor-acceptor systems ; Cage compounds ; Stelladione ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: -A number of condensations could be carried out using tricyclo[3.3.0.03,7]octane-2-one (stellanone, 4) and tricyclo[3.3.0.03,7]octane-2,6-dione (2,6-stelladione, 5) as starting materials. The components for condensations were 2-trimethylsilyl-1,3-dithiane (6), 1,1-bis(trimethylsilyl)-1H-cyclopropa[b]naphthalene (7), its 3,6-dimethoxy-substituted analogue 8, fluorene (12), xanthene (13), diethyl malonate (14), and malononitrile (15). The condensation reactions with 5 yielded mono- and disubstituted products, among them were the donor-acceptor-substituted 2,6-stellanes 33-35. The structures of 18 (prepared from stellanone and fluorene), 19, 24, 27, 31 and 32 (synthesized by condensation of 2,6-stelladione and 2-trimethylsilyl-1,3-dithiane and malononitrile, respectively) were determined by X-ray crystallography.
    Additional Material: 1 Ill.
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  • 68
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    Synthesis of ω-Nitro Acids and ω-Amino Acids by Ring Cleavage of α-Nitrocycloalkanones (1999)
    Weinheim : Wiley-Blackwell
    Liebigs Annalen 1999 (1999), S. 87-90 
    Details
    ISSN: 1434-193X
    Keywords: Water ; α-Nitrocycloalkanones ; ω-Nitro acids ; Surfactant ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: -The reaction of various α-nitrocycloalkanones 1 with aqueous 0.05 M NaOH, at 80 °C, in the presence of cetyltrimethylammonium chloride (CTACl) as a cationic surfactant, produces ω-nitro acids 2 in good yields. Reduction of the latter with HCOONH4/Pd-C, in methanol, at 80 °C affords ω-amino acids 3. The synthesis of methyl 9-oxodecanoate (8) is also reported.
    Additional Material: 2 Tab.
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  • 69
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    On the Selective O-Alkylation of Ambident Nucleophiles - The Synthesis of Thiohydroxamic Acid O-Esters by Phase-Transfer Reactions (1999)
    Weinheim : Wiley-Blackwell
    Liebigs Annalen 1999 (1999), S. 97-106 
    Details
    ISSN: 1434-193X
    Keywords: O-Alkylation ; Ambident nucleophile ; Thiazolethione ; Thiohydroxamic acid ; Phase-transfer reaction ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: -O-Alkylation of cyclic thiohydroxamic acids 1 and 3-5 has been studied with a view to developing an efficient method for the synthesis of N-(alkoxy)pyridine-2(1H)-thiones and N-(alkoxy)thiazole-2(3H)-thiones. Four issues have been addressed and the following conclusions can be drawn: (i) Thiones 1 and 5 exist as O-H acids in the solid state. (ii) According to NMR investigations (1H, 13C), the thione structures should be largely retained in CDCl3, [D6]DMSO, and CD3OD solutions of acids 1, 3-5, as is also the case for pyridinethione salts 2a-h. (iii) O-Alkylation of pyridinethione salts occurs in competition with S-alkylation. Selective O-alkylation is however possible, if thiohydroxamate salts with large countercations, such as M = NBu4, are treated with hard alkylating reagents in polar aprotic media. (iv) As tetrabutylammonium thiohydroxamates, such as 2f, are highly useful in the synthesis of cyclic thiohydroxamic acid O-esters, we have developed an efficient protocol for the preparation of N-(alkoxy)pyridine-2(1H)-thiones directly from acid 1 using phase-transfer conditions (alkyl halide or sulfonic acid ester, CH3CN, K2CO3, Bu4NHSO4). This method has proved particularly successful for the synthesis of N-(alkoxy)thiazole-2(3H)-thiones 11, 20-28, which were obtained in yields of up to 87%.
    Additional Material: 2 Ill.
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    Stereoselective Synthesis of the Pheromone (R)-(-)-Sulcatol, and Its Enantiopure (R)- and (S)-1-Mono-, -1,1-Di-, and -1,1,1-Trifluoro Analogues[1] (1999)
    Weinheim : Wiley-Blackwell
    Liebigs Annalen 1999 (1999), S. 117-127 
    Details
    ISSN: 1434-193X
    Keywords: Fluorine ; Pheromones ; Sulfoxides ; Sulcatol ; Asymmetric synthesis ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: -The pheromone (R)-(-)-sulcatol (10a) and three of its enantiomeric mono-, di-, and trifluoro analogues 10b-d have been synthesized, in six steps and with good overall yields, starting from chiral (R)-2-methyl-5-[(4-methylphenyl)sulfinyl]pent-2-ene (1) and commercially available fluorinated or non-fluorinated acetates.Supporting information for this article is available on the WWW under http://www.wileY-Vch.de/contents/jc_2046/1999/98375_s.pdf or from the author.
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  • 71
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    Stereoselective Synthesis of Enantiomerically Pure β-Fluoroalkyl γ-Butyrolactones by Sulfoxide-Directed Lactonization (1999)
    Weinheim : Wiley-Blackwell
    Liebigs Annalen 1999 (1999), S. 111-115 
    Details
    ISSN: 1434-193X
    Keywords: Fluorine ; Lactones ; Annulation ; Ketene ; Sulfoxides ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: -Enantiomerically pure α,α-dichloro β-fluoroalkyl γ-p-tolylthio γ-butyrolactones trans-6a-c have been obtained with excellent stereocontrol (〉 98:2) and enantiomeric purity (〉 98:2) by sulfoxide-directed lactonization (Marino's annu-lation reaction) of β-fluoroalkyl vinyl sulfoxides (R)-(E)-5a-c with dichloroketene. Highly chemoselective dechlorination and desulfurization reactions performed on trans-6c efficiently provided the β-chlorodifluoromethyl γ-butyrolactone (S)-8c, the absolute stereochemistry of which was determined by X-ray diffraction analysis of its γ-p-tolylthio precursor (2R,3S)-7c.
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  • 72
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    Nickel- or Iron-Catalyzed Coupling of Lithiated Methylthiomethyl p-Tolyl Sulfone with Lithiated Alkyl Sulfones to Give Methylthioalkenes (1999)
    Weinheim : Wiley-Blackwell
    Liebigs Annalen 1999 (1999), S. 163-165 
    Details
    ISSN: 1434-193X
    Keywords: Alkenes ; Methylthiomethyl sulfone ; Carbenoids ; Hetero-substituted carbanions ; Vinyl sulfides ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: -The reaction of methylthiomethyl p-tolyl sulfone with alkyl sulfones when lithiated gives regioselectively vinyl sulfides in high yields in the presence of Ni(acac)2 or Fe(acac)3.
    Additional Material: 2 Ill.
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    Experimental Evidence for Intramolecular Attractive Nonbonded C-F…H-C Interactions in 2′,3′-Dideoxy-4′-(fluoromethyl)nucleosides - Through-Space JCF and JHF NMR Coupling Constants, Correlation with Empirical Parameters of Solvent Polarity and Single-Crystal X-ray Structures (1999)
    Weinheim : Wiley-Blackwell
    Liebigs Annalen 1999 (1999), S. 187-196 
    Details
    ISSN: 1434-193X
    Keywords: Fluorinated dideoxynucleosides ; Through-space interactions ; Hydrogen bonds ; Long-range coupling constants ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: -A collection of 5′-O-benzyl-2′,3′-dideoxy-4′-(fluoromethyl)nucleosides carrying both purinic and pyrimidinic nucleobases (uracil, 5-Br-uracil, 5-O2N-uracil, 6-Cl-purine and inosine) were synthesized in both the α and the β form. Through-space-transmitted 6JCF NMR coupling constants between F and C-6 (pyrimidinic base) or C-8 (purinic base) were observed for all of the α anomers of the compounds examined, whilst the corresponding 7JHF coupling constants were resolved only for the 5-substituted uracil derivatives. The absolute values of all the through-space couplings were found to decrease monotonically with increasing solvent polarity (CDCl3, MeOD, [D6]acetone, [D6]DMSO). This trend suggests that the through-space interaction is mediated by an intramolecular (sp3)C-F…H-C(sp2) hydrogen bond. The possibility of any relevant solvent-induced conformational change influencing the F/base mutual spatial relationship in the molecules investigated was ruled out by heteronuclear steady-state 1H{19F}-NOE experiments. A linear correlation was observed between 6JCF and 7JHF coupling constants and the Kamlet-Taft's hydrogen bond basicity parameter β. The crystal structures of the α and β anomers of the 5-nitrouracil nucleoside show evidence that the H-6 of the nucleobase forms hydrogen-bond-like interactions involving the O-benzyl oxygen atom in the β anomer, and that in the case of the α anomer this is replaced by the F atom of the fluoromethyl group.
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  • 74
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    2,3-Dialkynyl-1,4-diazabuta-1,3-dienes as Novel π-Systems: Synthesis, Structure, and Electronic Properties (1999)
    Weinheim : Wiley-Blackwell
    Liebigs Annalen 1999 (1999), S. 205-214 
    Details
    ISSN: 1434-193X
    Keywords: Alkynes ; Cyclic voltammetry ; Diazabutadienes ; Electronic structure ; UV/Vis spectroscopy ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: -The introduction of alkynyl groups into the 2,3-positions of the 1,4-diazabuta-1,3-diene (DAD) backbone succeeds along two complementary synthetic routes either by condensing triisopropylsilyl-terminated dialkynyl-1,2-diones with primary aromatic amines or by a palladium-mediated alkynylation of bis(imidoyl chlorides). X-ray crystallographic analyses of two dialkynyl DAD derivatives reveals their planar (E-s-trans-E) conformations in the solid state. However, the central CC bond of both DAD backbones investigated has a length of 1.491(2) Å, and is therefore too long to indicate efficient delocalization across the DAD core. The UV/Vis spectra of dialkynyl DADs demonstrate that their absorptions in comparison to those of non-alkynyl DADs are bathochromically shifted by more than 40 nm, thereby demonstrating the suitability of the title compounds for developing NIR chromophores. The electron absorption properties of differentially N,N′-disubstituted dialkynyl DADs gave no indication for a push-pull effect across the DAD skeleton and suggest the ynimine moiety as the active chromophore of dialkynyl DADs. The electrochemical properties of the title compounds were determined by cyclo- and steady state voltammetry and show that introducing alkynyl groups leads to more easily reducible DAD systems. Again, the perception of dialkynyl DADs as covalently linked, but electronically decoupled ynimine units is corroborated by the redox potential of a differentially N,N′-disubstituted dialkynyl DAD. Similar conclusions were drawn from semiempirical MO (PM3) calculations of dialkynyl DADs.
    Additional Material: 5 Ill.
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    Synthesis and Biological Activity of Phosphonate Analogs of Mannose 6-Phosphate (M6P) (1999)
    Weinheim : Wiley-Blackwell
    Liebigs Annalen 1999 (1999), S. 447-450 
    Details
    ISSN: 1434-193X
    Keywords: Phosphonate analogs ; Mannose 6-phosphate (M6P) ; M6P receptors ; Recognition markers ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: -Two phosphonate analogs of mannose 6-phosphate (M6P) have been synthesized. The isosteric analog 1 was obtained by a Wittig-Horner reaction at position 6 of a sugar aldehyde. The non-isosteric analog 2 was obtained by a Michaelis-Arbuzov rearrangement of a 6-bromo derivative. In contrast to the non-isosteric analog 2, the isoster 1 was shown to bind to M6P receptors as effectively as does M6P itself, thus demonstrating the considerable potential of the system in drug design.
    Additional Material: 1 Ill.
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  • 76
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    Isopulegol as a Model Compound: Metalation and Substitution of an Allylic Position in the Presence of an Unprotected Hydroxy Function (1999)
    Weinheim : Wiley-Blackwell
    Liebigs Annalen 1999 (1999), S. 459-462 
    Details
    ISSN: 1434-193X
    Keywords: Electrophilic substitution ; Metalations ; Monoterpene ; Protective groups ; Superbase ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: -When treated with butyllithium and potassium tert-butoxide for 2 h at 0 °C in hexanes, the unsaturated monoterpenic alcohol isopulegol is simultaneously deprotonated at the hydroxy function and the allylic methyl group. The metaloxy allylmetal species thus generated can be silylated, alkylated, carboxylated and oxidized to afford the expected products in good to excellent yields. Thus, a specific protection of hydroxy groups is not required, alcohols being instantaneously converted by superbases into alcoholates.
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    Isolation of Cross-Coupling Products in Model Studies on the Photochemical Modification of Proteins by Tiaprofenic Acid (1999)
    Weinheim : Wiley-Blackwell
    Liebigs Annalen 1999 (1999), S. 497-502 
    Details
    ISSN: 1434-193X
    Keywords: Proteins ; Cross coupling ; Drug research ; Photochemistry ; Toxicology ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: -To gain insight into the chemical nature of drug-induced photoallergy, model studies have been carried out on the photochemical modification of proteins by tiaprofenic acid. Irradiation of decarboxylated tiaprofenic acid (DTPA) in the presence of p-cresol leads to C-C- and C-O-connected p-cresol “dimers”, together with DTPA hydrodimers. The p-cresol-DTPA cross-coupling product was not detected in this reaction. However, a product of this type is formed using a more hindered phenol, such as 2,6-di-tert-butylphenol. Similar results are obtained when tiaprofenic acid (TPA) or its methyl ester are used as photosensitizers. The observed formation of “dimers” can be related to protein photo-crosslinking, through the coupling of two tyrosine units. On the other hand, phenol-(D)TPA cross-coupling may be relevant to the understanding of drug-protein photobinding.
    Additional Material: 5 Ill.
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    Diastereoselective Addition of Chiral (2-Lithiophenyl)acetaldehyde Acetals to Various Imines as Key Step in the Asymmetric Synthesis of 1-Aryltetrahydroisoquinolines, Part 4 (1999)
    Weinheim : Wiley-Blackwell
    Liebigs Annalen 1999 (1999), S. 503-517 
    Details
    ISSN: 1434-193X
    Keywords: Enantiomerically pure (2-bromophenyl)acetaldehyde acetals ; Halogen-metal exchange ; Diastereoselective addition to imines ; Asymmetric synthesis ; Tetrahydroisoquinolines ; NMDA antagonists ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: -A novel asymmetric synthesis of 1-aryl-1,2,3,4-tetrahydroisoquinolines has been developed. The key step in this synthesis is the diastereoselective addition of homochiral (2-lithiophenyl)acetaldehyde acetals to the sulfonylimine 25 and to the arylimines 28 and 31. The best diastereoselectivity is obtained by addition of the bis(2-methoxypropan-2-yl)-substituted 1,3-dioxolane 6e to benzylidene-p-anisidine (31) with an HPLC-determined diastereomeric ratio 32c/33c = 92.1:7.9. The N-tosyl and the N-(4-methoxyphenyl) groups of the addition products 26d, 27d, 32c, and 33c are cleaved with sodium in liquid ammonia and ammonium cerium(IV) nitrate, respectively, to yield the primary amines 35 and 36. The acid-catalysed cyclization of the sulfonamides 26d and 27d and the carbamates 37 and 38, prepared from 35 and 36, leads to the enantiomerically pure dihydroisoquinolines 40 and 41, respectively. During the cyclization of the sulfonamides 26d, 27d and the carbamates 37, 38 the chiral auxiliary - the diol 39 - is cleaved unchanged and can be recovered in good yields.
    Additional Material: 4 Tab.
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    Ligand Effects on the Diastereoselectivities of Samarium Diiodide Promoted Pinacol Coupling (1999)
    Weinheim : Wiley-Blackwell
    Liebigs Annalen 1999 (1999), S. 565-572 
    Details
    ISSN: 1434-193X
    Keywords: Pinacol coupling ; Aldehydes ; Samarium diiodide ; 1,2-Diols ; Diastereoselectivity ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: -The samarium diiodide pinacol coupling of benzaldehyde and cyclohexanecarboxaldehyde in the presence of a variety of polyethylene glycols, including derivatives containing carbohydrates has been studied. Whereas such complexing agents allow for the formation of 1,2-diols, in the case of benzaldehyde the erythro-isomer predominates with diastereoselectivities of up to 7:1, while with cyclohexanecarboxaldehyde a stereoselectivity of up to 10:1 was observed but in favor of the threo-isomer. This divergence in the stereoselectivity of these two aldehydes suggests the presence of two different mechanisms occurring in these pinacol coupling reactions.
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  • 80
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    Thermal Rearrangements of Di- and Triphenyl-Substituted Benzocyclobutenes and Corresponding o-Quinodimethanes (1999)
    Weinheim : Wiley-Blackwell
    Liebigs Annalen 1999 (1999), S. 551-563 
    Details
    ISSN: 1434-193X
    Keywords: Benzocyclobutenes ; o-Quinodimethanes ; Pericyclic reactions ; Retrodisproportionation ; 9-Anthryl radicals ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: -7,8-Dimethoxy-7,8-diphenyl- (1c), 7,8-dimethyl-7,8-diphenyl- (1d), 7-methoxy-7,8,8-triphenyl- (1e), 7-methyl-7,8,8-triphenyl- (1f), 7-isocyano-7,8,8-triphenyl- (1g), and 7,7,8-triphenylbenzocyclobutene (1h) are amenable to a variety of thermal rearrangements following initial electrocyclic ring-opening to the corresponding 7,8-diphenyl- (2c,d) and 7,8,8-triphenyl-o-quinodimethanes (2e-h). meso-1c was found to undergo a facile meso/rac isomerization at room temperature, indicating that other processes such as a symmetry-forbidden disrotatory ring-opening or a stepwise reaction compete with the symmetry-allowed conrotatory process. An estimate of the energy profile of the 1c/2c reaction system was made by kinetic simulation in combination with oxygen trapping of the intermediate o-quinodimethanes (2c) and semiempirical PM3 calculations, and revealed that the barrier for the symmetry-forbidden pathway is merely about 4 kJ·mol-1 higher than that for the symmetry-allowed one. o-Quinodimethanes 2c, 2g, 2e, and 2h underwent further electrocyclic hexatriene-cyclohexadiene ring-closure to give 4a,10-dihydroanthracene derivatives at temperatures between 20 and 80 °C. The 4a,10-dihydroanthracenes were further transformed to 9,10-disubstituted anthracenes by elimination of methanol or HCN, as well as to 9,10-substituted 9,10-dihydroanthracene derivatives. ESR and ENDOR spectroscopic detection of related 9-anthryl radicals lends support to the view that 9,10-dihydroanthracene products are formed by a homolytic hydrogen-transfer reaction (retrodisproportionation). By way of contrast, the aforementioned transformations play only a minor role in the case of methyl-substituted benzocyclobutenes 1d, 1f as here they are overruled by faster 1,5-H shift reactions of the corresponding o-quinodimethanes 2d, 2f, leading to styrene derivatives.
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    Synthesis of Pentathiepanes and Isolation of the Conformers Based on High Inversion Barrier of the Pentathiepane Ring (1999)
    Weinheim : Wiley-Blackwell
    Liebigs Annalen 1999 (1999), S. 597-605 
    Details
    ISSN: 1434-193X
    Keywords: S Heterocycles ; Cyclic oligosulfides ; Pentathiepanes ; Conformational analysis ; Sulfuration ; Ring inversion ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: -Acenaphtho[1,2-a]acenaphthylene (1) was sulfurated with elemental sulfur to give a pentathiepane derivative (2). A dynamic NMR spectrum analysis revealed that the two naphthalene rings of 2 are chemically nonequivalent up to 100 °C. The pentathiepane ring of 2 was shown to adopt a chair conformation both in solution and crystals. In accordance with the NMR spectrum analysis, the sulfuration of 5-phenylacenaphtho[1,2-a]acenaphthylene (12) gave a pair of conformers (16a and 16b), which were isolated in pure form. The Friedel-Crafts acetylation of 2, followed by dithioacetalization with 1,2-ethanedithiol, also gave a pair of isolable conformers (18a and 18b). These two pairs of conformers isomerized, as a result of the ring inversion, to each other in solution at room temperature in the first-order kinetics. The activation parameters for this process, Ea, ΔH#, and ΔS#, were determined. Based on the experimental observations, a probable mechanism for the inversion process is proposed.
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    Cerium(III) Chloride Catalyzed Michael Reaction of 1,3-Dicarbonyl Compounds and Enones in the Presence of Sodium Iodide Under Solvent-Free Conditions (1999)
    Weinheim : Wiley-Blackwell
    Liebigs Annalen 1999 (1999), S. 617-620 
    Details
    ISSN: 1434-193X
    Keywords: Cerium(III) chloride heptahydrate ; Catalysis ; 1,3-Dicarbonyl compounds ; Enones ; Michael reactions ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: -Cerium(III) chloride heptahydrate in the presence of sodium iodide catalyses the Michael addition of 1,3-dicarbonyl compounds to α,β-unsaturated ketones and α,β-unsaturated aldehydes with extraordinary efficiency. The very mild conditions allow high chemoselectivity as shown by the absence of the typical side reactions, which can be observed in the conventional base-catalyzed processes. More interestingly, when at least one of the starting materials is liquid at room temperature, the reaction can also be performed without solvents. The CeCl3· 7 H2O/NaI catalyst system can be easily separated from the reaction mixture and it can be reused without an appreciable loss of activity. Advantages of the present procedure, which utilizes cheap and “friendly” reagents, over the previously reported ones, are discussed.
    Additional Material: 1 Ill.
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  • 83
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    Electronic Resource
    Synthesis of γ-Amino- and δ-Amino-Functionalised Ethers, Amines, or Silanes by Hydroaminomethylation of Heterofunctionalised Allylic Compounds (1999)
    Weinheim : Wiley-Blackwell
    Liebigs Annalen 1999 (1999), S. 653-660 
    Details
    ISSN: 1434-193X
    Keywords: Hydroaminomethylation ; Rhodium ; Catalysis ; Carbonylation ; Heterofunctionalised allylic compounds ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: -Heterofunctionalised allylic ethers 1, silanes 5, and amines 9 are hydroformylated in the presence of primary or secondary amines 2 to form the corresponding γ-amino- and δ-amino-functionalised compounds. The rhodium(I)-catalysed reaction sequence proceeds by aldehyde formation and subsequent reductive amination to generate the corresponding functionalised secondary or tertiary amines. This selective one-pot hydroaminomethylation procedure establishes access to γ-amino- and δ-amino-functionalised ethers, amines or silanes with potential biological activity.
    Additional Material: 4 Tab.
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  • 84
    Electronic Resource
    Electronic Resource
    Biomimetic Oxidation of Denaverine Hydrochloride (1999)
    Weinheim : Wiley-Blackwell
    Liebigs Annalen 1999 (1999), S. 679-683 
    Details
    ISSN: 1434-193X
    Keywords: Biomimetic oxidations ; Cytochrome P450 ; Metalloporphyrins ; Denaverine ; Metabolism ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: -The behavior of denaverine (1) in various chemical model systems based on metalloporphyrins as catalysts was investigated to determine the possible oxidative metabolism. The resulting derivatives were compared to a biological model system and in vivo metabolism in rat and human.
    Additional Material: 2 Tab.
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  • 85
    Electronic Resource
    Electronic Resource
    A Comparison of Chemical and Photochemically Induced Reduction of Some 2(4),5-Dihydro-1,2,4-triazines and Aromatic 1,2,4-Triazines (1999)
    Weinheim : Wiley-Blackwell
    Liebigs Annalen 1999 (1999), S. 685-689 
    Details
    ISSN: 1434-193X
    Keywords: Single-electron transfer ; Ring contractions ; 1,4-Dihydro-1,2,4-triazine ; Photochemical reduction ; Chemical reduction ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: -Chemical reduction (Zn/AcOH) of the arene 1 and of 2(4),5-dihydro-1,2,4-triazine 7 has been reinvestigated, resulting in the amendment of literature data concerning this reaction. Chemical, electrochemical, and photochemically induced reductions and ring contractions of 1,2,4-triazine derivatives have been compared. The first example of a triaryl-1,4-dihydrotriazine has been prepared. Some further evidence is presented that supports the proposed mechanism of the photochemically induced reduction and ring contraction of 1,2,4-triazines.
    Additional Material: 2 Tab.
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  • 86
    Electronic Resource
    Electronic Resource
    Preparation of 2,3,5-Tri-O-benzyl-4-thio-L-arabino-furanosides and the Corresponding 4′-Thionucleoside Analogues (1999)
    Weinheim : Wiley-Blackwell
    Liebigs Annalen 1999 (1999), S. 691-696 
    Details
    ISSN: 1434-193X
    Keywords: Carbohydrates ; 4-Thiofuranosides ; Nucleosides ; Reaction mechanisms ; NOE measurements ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: -1-O-Acetyl-2,3,5-tri-O-benzyl-4-thio-L-arabino-furanose (9) has been prepared from D-xylose via the 1,4-dithio-L-arabino-furanoside 8. The crucial step of the reaction, i.e. the intramolecular cyclization of the open-chain dithioacetal 5, has been achieved in a yield of 90% by applying tetrabutylammonium iodide as promoter. Reaction of 9 with bis(trimethylsilyl)uracil or -thymine led to the benzyl derivatives 12 and 13 from which the deprotected 4′-thionucleoside analogues 14 and 15 have been prepared by debenzylation with boron tribromide.
    Additional Material: 1 Ill.
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  • 87
    Electronic Resource
    Electronic Resource
    Steric and Electronic Effects in the Diastereoselective Catalytic Epoxidation of Cyclic Allylic Alcohols with Methyltrioxorhenium (MTO) (1999)
    Weinheim : Wiley-Blackwell
    Liebigs Annalen 1999 (1999), S. 785-790 
    Details
    ISSN: 1434-193X
    Keywords: Epoxidations ; Diastereoselectivity ; Allylic alcohols ; Homogeneous catalysis ; Methyltrioxorhenium ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: -The steric effects of allylic substituents in the epoxidations with methyltrioxorhenium/urea/hydrogen peroxide adduct (MTO/UHP) have been assessed for a series of 3-alkyl-substituted cyclohexenes. The trans selectivity increases with the size of the substituent and the diastereoselectivities follow an excellent linear correlation with the steric substituent constants of Taft (Es) or Charton (ν). Good cis selectivity is observed in the epoxidation of the cyclic allylic alcohols 2-cyclopentenol and 2-cyclohexenol due to a hydroxy-directing effect through hydrogen bonding; however, for 2-cycloheptenol and 2-cyclooctenol hydrogen bonding is ineffective and steric interactions cause a higher trans selectivity. The conformationally fixed cis- and trans-5-tert-butyl-2-cyclohexenols serve as suitable substrates for gauging the dihedral angle of the transition states for the oxygen transfer in these epoxidations. Thus, the MTO/UHP oxidant favours a quasi-equatorial arrangement of the hydroxy group for effective hydrogen bonding (hydroxy-group directivity), in analogy to m-chloroperbenzoic acid (m-CPBA) and dimethyldioxirane (DMD), and a dihedral angle of ca. 130° is suggested.
    Additional Material: 2 Ill.
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  • 88
    Electronic Resource
    Electronic Resource
    Catalytic Oxyselenenylation-Deselenenylation Reactions of Alkenes - Stereoselective One-Pot Conversion of 3-Alkenols into 2,5-Dihydrofurans (1999)
    Weinheim : Wiley-Blackwell
    Liebigs Annalen 1999 (1999), S. 797-803 
    Details
    ISSN: 1434-193X
    Keywords: Phenylselenenyl sulfate ; Selenium-catalyzed reactions ; Stereoselective syntheses ; Dihydrofurans ; Tetrahydrofurans ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: -A stereoselective multi-step one-pot procedure for converting 2-methoxycarbonyl-3-alkenols into 3-methoxycarbonyl-2,5-dihydrofurans, using only catalytic amounts of diphenyl diselenide and an excess of ammonium persulfate, has been developed. The erythro alkenols give the trans dihydrofurans, while the threo stereoisomers give the corresponding cisproducts. The configurations of the starting alkenols were deduced from those of the intermediate phenylseleno tetrahydrofurans, which were independently obtained from reactions of the alkenols with stoichiometric amounts of phenylselenenyl sulfate.
    Additional Material: 3 Tab.
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  • 89
    Electronic Resource
    Electronic Resource
    The Synthesis of Imidazol Sugars Which Mimic Cyclic Carboxonium Ions Formed During the Glycosidase-Catalysed Hydrolysis of Oligo and Polysaccharides (1999)
    Weinheim : Wiley-Blackwell
    Liebigs Annalen 1999 (1999), S. 893-898 
    Details
    ISSN: 1434-193X
    Keywords: Carbohydrates ; Amino sugars ; Imidazole ; Glycosidases ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: -Some naturally occurring carbohydrates, of which several hydroxy groups had been selectively protected, were condensed with formamidine to give the expected imidazole derivatives in the D-arabino (9), D-lyxo (12), L-xylo (17), D-threo (21), and in the L- and D-erythro (24) series. Introduction of a strong leaving group at the remaining free alcohol function of these products led at once to intramolecular SN2 cyclisation to the corresponding bicyclic aza sugar derivatives. This was followed by total deprotection to give the target aza sugars in the L-xylo (7), L-ribo (14), D-arabino (19), as well as in the D-threo (22) and the L- and D-erythro (26) series. Inhibitory assays with four glycosidases showed that the D-arabino aza sugar 19 is the only potent inhibitor (for an α-mannosidase of jack bean).
    Additional Material: 1 Tab.
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  • 90
    Electronic Resource
    Electronic Resource
    Preparation and Characterization of Bridged Naphthoxazinium Salts (1999)
    Weinheim : Wiley-Blackwell
    Liebigs Annalen 1999 (1999), S. 923-930 
    Details
    ISSN: 1434-193X
    Keywords: Bridged benzo[a]phenoxazinium salts ; Diazo compounds ; Cyclocondensation ; Absorption ; Fluorescence ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: -By condensation of bridged 4-arylazo-substituted 3-hydroxyanilines 18 and bridged or unbridged 4-arylazo-substituted 1-naphthylamines 19-23 with bridged 1-naphthylamines 15-17 and 3-aminophenols 14, respectively, in the presence of perchloric acid, bridged naphthoxazinium perchlorates 24-30 have been prepared. The spectral properties of the products have been compared with those of the bridged phenoxazinium salt 31 as well as with data for some unbridged analogues.
    Additional Material: 1 Ill.
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  • 91
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    Electronic Resource
    3-Trifloxy-3-trifluoromethylpropeniminium Triflate: Reaction with Aromatic Amines - An Efficient Synthesis of 2-Trifluoromethylquinolines (1999)
    Weinheim : Wiley-Blackwell
    Liebigs Annalen 1999 (1999), S. 937-941 
    Details
    ISSN: 1434-193X
    Keywords: Iminium salts ; Triflic anhydride ; Arylamines ; 2-Trifluoromethyl quinolines ; 3-Trifluoromethyl-cinnamaldehydes ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: -The reaction of iminium triflates 2 and 7 with various aromatic amines were investigated. The 2-Rf-substituted quinolines 3 and 8 were prepared in excellent yields by the reaction of 2 and 7, respectively, with substituted anilines. The reactions of 2 and 7 with diarylamines proceeds, suprisingly, to afford the corresponding 3-Rf-substituted cinnamaldehydes 4 and 9.
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  • 92
    Electronic Resource
    Electronic Resource
    Synthesis Mediated by Ring-Closing Metathesis - Applications in the Synthesis of Azasugars and Alkaloids (1999)
    Weinheim : Wiley-Blackwell
    Liebigs Annalen 1999 (1999), S. 959-968 
    Details
    ISSN: 1434-193X
    Keywords: Heterocycles ; Alkaloids ; Castanospermine ; Metathesis ; Azasugars ; Manzamine A ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: -The application of the ring-closing metathesis (RCM) reaction to the construction of a wide variety of nitrogen-containing ring systems is described. The examples include pyrrolizidine, indolizidine, and quinolizidine derivatives related to azasugars. A formal total synthesis of castanospermine (5) is presented. The utilisation of two RCM steps in the synthetic sequence leading to the multicyclic ABCDE nucleus 7 of the complex alkaloid manzamine A (6) is discussed.
    Additional Material: 3 Ill.
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  • 93
    Electronic Resource
    Electronic Resource
    Hydrogen Transfer Hydrozirconation of Alkenes with iBuZrCp2Cl Catalyzed by Lewis-Acidic Metal Compounds Containing Al, Zn, Si, Ag, and Pd (1999)
    Weinheim : Wiley-Blackwell
    Liebigs Annalen 1999 (1999), S. 969-971 
    Details
    ISSN: 1434-193X
    Keywords: Hydrogen transfer ; Zirconium ; Alkenes ; Isobutylzirconocene chloride ; Lewis acid catalysis ; Lewis acid catalysis ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: -The hydrozirconation reaction of monosubstituted alkenes with iBuZrCp2Cl can be significantly accelerated by catalytic amounts of various Lewis acidic metal compounds, most notably AlCl3, Me3SiI, and Pd complexes, such as Li2PdCl4 and Cl2Pd(PPh3)2.Supporting information for this article is available on the WWW under -http://www.wileY-Vch.de/contents/jc_2046/1999/99042_s.pdf or from the author.
    Additional Material: 1 Tab.
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  • 94
    Electronic Resource
    Electronic Resource
    Synthesis of the Enantiomers of (Z)-21-Methyl-8-pentatriacontene, the Major Component of the Female-Produced Contact Sex Pheromone of the Yellow-Spotted Longicorn Beetle, Psacothea hilaris (1999)
    Weinheim : Wiley-Blackwell
    Liebigs Annalen 1999 (1999), S. 981-984 
    Details
    ISSN: 1434-193X
    Keywords: Alkenes ; Chirality ; Longicorn beetle ; Pheromones ; Psacotheahilaris ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: -Both the enantiomers of (Z)-21-methyl-8-pentatriacontene (1), the major component of the female-produced contact sex pheromone of the yellow-spotted longicorn beetle (Psacotheahilaris), were synthesized by starting from the enantiomers of citronellol (2)
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  • 95
    Electronic Resource
    Electronic Resource
    Pseudorotaxanes and Catenanes Containing a Redox-Active Unit Derived from Tetrathiafulvalene (1999)
    Weinheim : Wiley-Blackwell
    Liebigs Annalen 1999 (1999), S. 985-994 
    Details
    ISSN: 1434-193X
    Keywords: Catenanes ; Molecular machines ; Pseudorotaxanes ; Template-directed synthesis ; Tetrathiafulvalenes ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: -Two bis(2-oxy-1,3-propylenedithio)tetrathiafulvalene-containing acyclic polyethers and two macrocyclic polyethers, each incorporating one bis(2-oxy-1,3-propylenedithio)tetrathiafulvalene unit and one p-phenylene ring, have been synthesized. The two acyclic polyethers are bound by cyclobis(paraquat-p-phenylene) with pseudorotaxane geometries in solution. The two macrocyclic polyethers have been mechanically interlocked with this tetracationic cyclophane to form [2]catenanes in a kinetically controlled self-assembly process. The X-ray crystallographic analysis of one of the two [2]catenanes and 1H-NMR-spectroscopic studies of both compounds showed that the p-phenylene ring of the macrocyclic polyether is located inside the cavity of the tetracationic cyclophane, while the bis(2-oxy-1,3-propylenedithio)tetrathiafulvalene unit resides alongside. The [2]pseudorotaxanes and [2]catenanes show broad bands around 780 nm, arising from the charge-transfer (CT) interaction between the electron-donor tetrathiafulvalene-(TTF-)type unit and the electron-acceptor units of the tetracationic cyclophane. 1H-NMR-spectroscopic studies have shown that the [2]pseudorotaxanes dissociate into their separate components upon oxidation of the TTF-type unit, as a result of disruption of the CT interaction and electrostatic repulsion between the tetracationic host and the newly formed monocationic guest. The subsequent reduction of the guest to its neutral state affords back the pseudorotaxane-type complex restoring the original equilibrium. The results obtained from electrochemical experiments are consistent with the reversible, redox-driven dethreading/rethreading process observed by 1H-NMR spectroscopy. Variable-temperature 1H-NMR-spectroscopic investigations have revealed two dynamic processes, both involving the relative movements of the mechanically interlocked components in the [2]catenanes. The two consecutive oxidation processes involving the TTF-type unit, observed electrochemically, are displaced toward more positive potentials compared with the free cyclic polyethers. The two reversible two-electron reduction processes, characteristic of free cyclobis(paraquat-p-phenylene), separate into four reversible one-electron processes because of the topological difference between the “inside” and “alongside” electron-acceptor units in the [2]catenane.
    Additional Material: 11 Ill.
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  • 96
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    Electronic Resource
    Totally Regio- and Stereoselective P-O-to-P-C Rearrangement in the Synthesis of Chiral P-(o-Hydroxyaryl)diazaphospholidine P-Oxides (1999)
    Weinheim : Wiley-Blackwell
    Liebigs Annalen 1999 (1999), S. 1099-1105 
    Details
    ISSN: 1434-193X
    Keywords: Asymmetric synthesis ; Chiral synthons ; P-(o-Hydroxyaryl)diazaphospholidine P-oxides ; Rearrangements ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: -The totally regio- and stereoselective P-O-to-P-C rearrangement in the synthesis of various chiral P-(o-hydroxyaryl)diazaphospholidine P-oxides has been investigated. This reaction proceeds with excellent yields ranging from 72 to 92%, total retention of configuration at the phosphorus atom, and complete regioselectivity. An exception was found with naphthyl derivatives, which gave mixtures of two regioisomers. In all cases, the products generated have been unambiguously characterized by 1H-, 13C-, and 31P-NMR spectroscopy as well as by X-ray-diffraction analysis.
    Additional Material: 3 Ill.
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  • 97
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    Electronic Resource
    Palladium-Catalyzed Cyclocarbonylation of o-Ethynylphenols and Vinyl Triflates To Form 3-Alkylidene-2-coumaranones (1999)
    Weinheim : Wiley-Blackwell
    Liebigs Annalen 1999 (1999), S. 1137-1141 
    Details
    ISSN: 1434-193X
    Keywords: Cyclocarbonylation ; Alkynes ; Catalysis ; Palladium ; Vinyl triflates ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: -o-Ethynylphenols react with vinyl triflates, in the presence of tetrakis(triphenylphosphane)palladium(0) and under carbon monoxide, to form 3-alkylidene-2-coumaranones in good yield.
    Additional Material: 1 Tab.
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  • 98
    Electronic Resource
    Electronic Resource
    S-Linked Thiomimetics of Phytoalexin-Elicitor-Active, Branched Oligosaccharides, Their Synthesis, Protein-Binding Ability and Phytoalexin-Inducing Activity (1999)
    Weinheim : Wiley-Blackwell
    Liebigs Annalen 1999 (1999), S. 1143-1152 
    Details
    ISSN: 1434-193X
    Keywords: Sulfur-linked thiooligosaccharides ; Oligosaccharin thio analogs ; Phytoalexin elicitor thio analogs ; Soybean glucan-binding assays ; Structure-activity relationships ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: -The sulfur-linked pentathiohexasaccharide 3I,3IV-di-β-D-glucopyranosylthiogentiotetraose (12) has been prepared by a convergent approach involving the reaction of 1,2,4-tri-O-acetyl-6-deoxy-6-iodo-3-S-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)-3-thio-β-D-glucopyranose (10) with the sodium salt of 2,3,4-tri-O-acetyl-6-S-[2,4-di-O-acetyl-3,6-di-S-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)-3,6-dithio-β-D-glucopyranosyl]-1,6-dithio-β-D-glucopyranose (4). A further reaction, involving the sodium salt of the peracetylated β-1-thio derivative of 12 with 1,2,3,4-tetra-O-acetyl-6-deoxy-6-iodo-β-D-glucopyranose (26), afforded the homologous sulfur-linked hexathioheptasaccharide 3II,3V-di-β-D-glucopyranosylthiogentiopentaose (28). Related sulfur-linked positional isomers 3II,3IV-di-D-β-glucopyranosylthiogentiotetraose (34) and 3III,3V-di-β-D-glucopyranosylthiogentiopentaose (39) have been prepared using analogous synthetic strategies. Thus, SN2 displacement of the iodine atom in 10 by the sodium salt of 2,4-di-O-acetyl-3,6-di-S-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)-1,3,6-trithio-β-D-glucopyranose afforded a tetrathiopentasaccharide, which resulted in the pentathiohexasaccharide 34 by a sequence of reactions involving the 1-thioglycose 32 in reaction with 26. The hexathioheptasaccharide 39 was obtained conveniently by the reaction of 26 with the acetylated 1-thio-6I, 3II, 6II, 3IV, 6IV-pentathio derivative 37, followed by deacylation. The four isomeric pentathiohexa- and hexathioheptasaccharides 12,34 and 28,39, respectively, were all found to be active in eliciting phytoalexin accumulation in soybean cotyledon tissue and in binding to a glucan-binding protein of soybean, although to a lesser extent than the corresponding O-oligosaccharides, the alternate thiohexa- and thioheptasaccharides 12,28 being more active as compared to the geminally branched isomers 34,39.
    Additional Material: 3 Tab.
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  • 99
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    Electronic Resource
    Intramolecular Copper- and Rhodium-Mediated Carbenoid Reactions of α-(Propargyloxy)silyl-α-diazoacetates (1999)
    Weinheim : Wiley-Blackwell
    Liebigs Annalen 1999 (1999), S. 1213-1221 
    Details
    ISSN: 1434-193X
    Keywords: Diazo compounds ; Carbenes ; Carbenoids ; Silicon ; Heterocycles ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: -Copper(I) triflate catalyzes the transformation of α-[(2-alkynyl)oxy]silyl-α-diazoacetates 1a-g into 1,2-bis(2,5-dihydro-1,2-oxasilol-4-yl)ethenes 2 and/or 2H-1,2-oxasilines 3. With rhodium(II) perfluorobutyrate as catalyst, 1a-e furnish only 3 but no 2. Bicyclic 2-methoxyfurans 6 are formed when 1a,c,e (containing terminal alkyne functions) are treated with catalytic amounts of copper(I) chloride. The experimental observations are explained in terms of metal-mediated intramolecular cyclopropenation and subsequent metal-assisted ring-opening of the strained bicyclic cyclopropene leading to vinylcarbene-metal complexes. An unusual autoxidation of 2H-1,2-oxasilines 3a,c,e is also described.
    Additional Material: 1 Ill.
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  • 100
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    Electronic Resource
    Syntheses of Cyclobutane Derivatives: Total Synthesis of (+) and (-) Enantiomers of the Oleander Scale Aspidiotus nerii Sex Pheromone (1999)
    Weinheim : Wiley-Blackwell
    Liebigs Annalen 1999 (1999), S. 1201-1211 
    Details
    ISSN: 1434-193X
    Keywords: Pheromones ; Aspidiotus nerii ; Sex attractant ; Cyclobutane ; Enantiomeric purity ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: -Synthesis of both enantiomers of the Aspidiotus nerii sex pheromone and their diastereomers has been achieved using, as a key step, an intramolecular ester enolate alkylation reaction for the formation of the cyclobutane ring with a good control of the relative configurations of the asymmetric centers. Stereoselective synthesis of a number of other trisubstituted cyclobutane derivatives also proves the versatility of the methodology used for the synthesis of the Aspidiotus nerii sex pheromone.
    Additional Material: 2 Ill.
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