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  • 1990-1994  (114)
  • American fiction., lcsh
  • English poetry., lcsh
  • chemotherapy
  • 1
    ISSN: 1436-2813
    Keywords: portal vein ; liver micrometastasis ; chemotherapy ; 5-fluorouracil
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To clarify the significance of prophylactic portal vein chemotherapy for hepatic metastases, the correlation between the timing of the portal infusion and the growth of liver micrometastases was examined in a rat model. Male Donryu rats weighing 160-180g were first inoculated intraportally with 5 X 106 ascites hepatoma AH60C cells, following which an intraportal infusion of 5-fluorouracil (5-FU) 20 mg/kg/day with heparin 100 U/kg/day was given over 5 days, commencing on day 0, 3, and 6, in groups A, B, and C, respectively. Compared with a control group of rats which received no treatment, a significant inhibition of tumor growth and prolongation of survival time were observed in groups A (P 〈 0.01) and B (P 〈 0.05); however, group C, in which the mean diameter of the micrometastases was 0.52 ±0.10 mm at the commencement of the portal infusion, showed no therapeutic response. These results suggest that prophylactic portal vein chemotherapy should be given to prevent the lodgement of tumor cells in the portal system and inhibit their initial proliferation, rather than to destroy established micrometastases.
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  • 2
    ISSN: 1436-0691
    Keywords: hepatocellular carcinoma ; partial hepatectomy ; recurrence ; prevention ; chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A major problem in treating hepatocellular carcinoma (HCC) is intrahepatic recurrence after partial hepatectomy, despite the relatively early detection now possible due to recent developments in non-invasive diagnostic modalities. The present study evaluated the usefulness of preventive therapy for intrahepatic recurrence of HCC. In order to suppress intrahepatic recurrence in HCC patients at high risk of recurrence after tumor removal, we performed preventive transarterial chemotherapy in 23 such patients. Doxorubicin, at a dose of 0.5 mg/kg body weight, was administered, via a catheter inserted at the junction of the common hepatic artery and the gastroduodenal artery, every 2 weeks for the first 2 months, and every month thereafter for at least 1 year. The control group consisted of 30 patients with similar risk of recurrence who underwent partial hepatectomy during the same period without receiving transarterial preventive therapy. The 1-, 2-, 3-, and 5-year cumulative cancer-free survival rates in patients who received transarterial preventive chemotherapy after partial hepatectomy were 87.0%, 47.1%, 21.2%, and 21.2%, respectively, compared to 53.3%, 30.0%, 20.0%, and 13.3%, respectively, in the control group (P〈0.05). The 1-, 2-, 3-, and 5-year cumulative overall survival rates were 95.7%, 81.2%, 58.4%, and 48.7%, respectively, in the preventive chemotherapy group, compared to 70.0%, 49.4%, 41.7%, and 19.5%, respectively, in the control group (P〈0.05). Thus, the present study demonstrates the limited but significant effect of preventive transarterial chemotherapy for the intrahepatic recurrence of HCC after partial hepatectomy.
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  • 3
    ISSN: 1436-2813
    Keywords: activated charcoal ; cisplatin ; drug delivery system ; esophageal cancer ; chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In this study, 1500AA, an activated charcoal with a strong affinity for the lymphatic system, was examined for its ability to deliver chemotherapy to metastatic lymph nodes. First, the anticancer effect on metastatic lymph nodes was assessed in an experiment using the mouse mammary tumor, MM48. Pathological examination of the inguinal lymph nodes revealed a metastatic rate of 50% in the group given cisplatin (CDDP)-saline, but 20% in the group given CDDP-charcoal. Next, in a canine model, CDDP dissolved in normal saline was administered directly into the mediastinum, and CDDP was given with fine particles of activated charcoal in the same manner in the other group. The concentration of CDDP in the lymph nodes and the plasma rapidly increased to peak in 10 min in the CDDP-saline group, whereas it increased slowly to peak in 20–30 min in the CDDP-charcoal group. Moreover, the CDDP-charcoal group was found to have a much higher concentration of CDDP in the lymph nodes than the CDDP-saline group.
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Investigational new drugs 12 (1994), S. 49-52 
    ISSN: 1573-0646
    Keywords: metastatic colorectal cancer ; chemotherapy ; GM-CSF
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The response rate of patients with metastatic colorectal cancer to the 4-drug combination [5-Fluorouracil (5-FU), dacarbazine, vincristine and bis-chloronitrosourea given 5 weekly (FIVB)] was better than the response rate to 5-FU. The dose limiting toxicity of the FIVB was myelosuppression. The present study investigates the effect of FIVB given with GM-CSF so that drug cycles could be given every 4 weeks. Thirty-five ambulatory patients with measurable metastatic colorectal cancer were treated with FIVB plus GM-CSF 4 weekly. All patients were evaluable for toxicity. Among the 163 cycles given only 4 were delayed because of leucopenia and 8 cycles were delayed because of gastrointestinal (GI) toxicity. A 50% dose reduction was given to 10 patients who had Grade 2 and 3 GI toxicity. Four of the 35 patients developed thromboembolic complications, 2 of which were lethal. Two patients were not evaluable for response as they were removed from study early because of toxicity. There were 2 complete responses and 6 partial responses. The median time to treatment failure was 3.8 months and median survival time 9.9 months. The addition of GM-CSF to FIVB decreased the expected leucopenia allowing drug treatment to be given 4 weekly to most patients. GI toxicity was dose limiting. Despite the increased dose intensity that could be delivered (to two thirds of patients), response rates were not definitely increased, no survival benefit was seen and important thromboembolic complications occurred.
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Investigational new drugs 12 (1994), S. 133-136 
    ISSN: 1573-0646
    Keywords: colorectal carcinoma ; chemotherapy ; alkylating agent
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Background Relatively few studies have examined the activity of alkylating agents in the treatment of advanced colorectal adenocarcinoma. Recent reports have suggested possible therapeutic activity for high-dose intravenous melphalan administered with autologous bone marrow transplantation (BMT) support. We conducted a phase II study to determine the efficacy of administering intravenous melphalan at doses that do not require BMT support in patients with advanced colorectal adenocarcinoma. Patients and methods Fifteen patients with histologically proven, bidimensionally measurable disease were treated. The starting dose of melphalan was 30 mg/m2, with dose escalation permitted. Results No objective responses were observed. Toxic effects were primarily reversible granulocytopenia and thrombocytopenia. There were no treatmentassociated deaths. Conclusion Melphalan's lack of efficacy at the doses administered does not disprove the steep chemotherapy dose-response relationship postulated for many solid tumors. However, we feel that it is unlikely that repetitive courses of high dose melphalan with autologous BMT support will be a practical approach to the management of advanced colorectal adenocarcinoma.
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  • 6
    ISSN: 1573-0646
    Keywords: pancreatic cancer ; AMAP ; 773U82 ; chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Pancreatic cancer is the fifth leading cause in cancer related death among adults in the United States. Thirtythousand new cases of pancreatic cancer are diagnosed each year, most are metastatic at diagnosis and no effective systemic therapy is available. 773U82 mesylate is one of a series of compounds (arylmethylaminopropanediols-AMAPS) which was synthesized at the Wellcome Research Laboratories. AMAPS bind to DNA, show evidence of topoisomerase 2 inhibition and are active in a variety of murine and human preclinical screens. Based on these data a phase II trial of 773U82 mesylate administered at 800 mg/ m2 daily × 3 at a 4 h infusion repeated every three weeks was carried out. Patients eligible for these trials had histologic proof of adenocarcinoma, good performance status, and normal organ function. This was a multi-institutional trial. Nineteen patients were entered; 15 patients were fully eligible and 4 were ineligible, but were evaluated. Thirteen patients were fully evaluable for response and no response was seen. Median time to progressive disease among eligible patients was 56 days. Toxicity of 773U82 mesylate was myelosuppression which was not prohibitive. 773U82 mesylate is not active in pancreatic cancer.
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  • 7
    ISSN: 1573-0646
    Keywords: breast cancer ; dipyridamole ; mitoxantrone ; 5-FU ; leukovorin ; chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Based upon the hypothesis that dipyridamole would potentiate the cytotoxicity of mitoxantrone and the combination of 5-fluorouracil (5-FU) and leukovorin, we performed a phase I/II trial of the combination of dipyridamole, 5-FU, leukovorin, and mitoxantrone in patients with metastatic breast cancer. The dose of dipyridamole was fixed at 175 mg/m2 by mouth every 6 h (700 mg/m2/day), based upon a previous phase I trial of oral dipyridamole with 5-FU and leukovorin. Dipyridamole therapy began 24 h prior to the first dose of chemotherapy and continued until 24 h after the last dose of chemotherapy for each course of treatment. At the initial dose level, leukovorin 200 mg/m2 was given intravenously immediately prior to 5-FU 375 mg/ m2 intravenously on days 1–5. Mitoxantrone 6 mg/m2 was given as a single dose on day 3. Unacceptable toxicity was observed at this dose level, leading to successive dose decrements rather than dose increments. The maximum tolerated dose was leukovorin 200 mg/m2 days 1–2, 5-FU 375 mg/m2 days 1–2, mitoxantrone 6 mg/m2 on day 2, and dipyridamole 175 mg/m2 every 6 h on days 0–3. Two responses were produced in 15 patients. This regimen is not recommended for further investigation in the treatment of breast cancer.
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Journal of neuro-oncology 20 (1994), S. 111-120 
    ISSN: 1573-7373
    Keywords: glioma ; chemotherapy ; radiotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Although primary brain tumors represent an important cause of cancer related mortality in the United States, advances in the treatment of these tumors has been slow and has generally lagged behind that of most systemic tumors. One of the major reasons for this is the paucity of well conducted, prospective radiation and chemotherapy trials. For the brain tumor trials that have been conducted, small patient numbers, heterogeneous patient populations, and non-uniformity of response criteria, have made the current clinical data base difficult to interpret. Data from several prospective, multi-institutional randomized trials have defined a role for radiation therapy in the treatment of malignant gliomas and on-going trials will help define refinements in technique. Although there does appear to be a place for the use of chemotherapy in the treatment of a subgroup of patients with malignant gliomas, its role for the majority of patients remains unclear. Only through better understanding of the biology of these tumors, more effective therapies, and the implementation of better clinical trial design can we hope to make significant progress in the treatment of malignant gliomas.
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Journal of neuro-oncology 20 (1994), S. 155-163 
    ISSN: 1573-7373
    Keywords: chemotherapy ; high grade brain tumors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Conventional treatment of malignant high grade gliomas includes maximal resection followed by external beam radiotherapy. The addition of adjuvant chemotherapy has provided little improvement in the median duration of survival for these patients, particularly those patients with glioblastoma multiforme. The failure of conventional dose chemotherapy to improve the outcome of patients with high grade brain tumors has led several investigators to utilize high dose chemotherapy in order to overcome the limited benefit seen with conventional dose therapy which is due to intrinsic drug resistance as well as the impermeability of blood brain barrier. The majority of published studies utilizing this approach suggest that the addition of high dose chemotherapy with bone marrow transplant is of marginal benefit. However, most of these trials include small numbers of patients with advanced, refractory disease. A few trials have been reported utilizing high dose therapy in an adjuvant setting and the data from these studies are somewhat more promising. This review will analyze these studies and also discuss possible modifications of this approach in order to improve this aggressive treatment for patients who otherwise would have a dismal prognosis.
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  • 10
    ISSN: 1573-7373
    Keywords: O6-alkylguanine-DNA alkyltransferase ; chloroethylnitrosourea ; malignant glioma ; chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Activity of the DNA repair protein O6-alkylguanine-DNA alkyltransferase (AGT) is an important determinant of responsiveness of tumor cells to chloroethylnitrosoureas (CENUs), representative chemotherapeutic agents for primary malignant gliomas. In order to assess the real states of this repair protein in human malignant gliomas, we assayed AGT activity in surgically extirpated 42 malignant glioma samples and studied the distribution of the activity under certain clinical conditions. There were wide variations in AGT activity between individuals. No significant difference in AGT activity on average was seen either between glioblastoma and anaplastic astrocytoma, nor between primary and recurrent tumors. Among 42 malignant gliomas, 7 samples (16.7%) had low AGT activity less than 0.1 pmoles/mg protein. In the case of glioblastoma, tumors possessing higher AGT activity tended to be less responsive to post-operation remission-induction therapy including CENUs. The result of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) chemosensitivity assay by using the corresponding surgical specimens suggested a close relationship between cellular resistance to CENUs and AGT activity. It was found to be unlikely that a short term administration of CENUs had a significant effect on AGT activity of brain tumors in human body. We could detect a bit of definite evidences of the relevance of AGT to resistance to CENUs and need to conduct further investigations for other resistance factors.
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  • 11
    ISSN: 1573-7373
    Keywords: chemotherapy ; meningioma ; radiation-induced osteosarcoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A case of effective chemotherapy in postirradiation sarcoma is reported. A 30-year-old woman underwent a subtotal resection of a benign mixed meningioma followed by a course of radiotherapy. Five years later she developed a skull tumor which was resected. Histological study showed sarcomatous change corresponding most likely to a postirradiation osteosarcoma. Adjuvant chemotherapy (methotrexate, carboplatin, and VP16) was given. A progression occurred 8 months later and the patient was treated unsuccessfully with tamoxifen, LHRH, and later with high dose methotrexate and carboplatin. Six months later a lung metastasis was discovered and she received four cycles of IVP (ifosfamide, vepeside, cisplatin) alternating with IVA (ifosfamide, vepeside, adriamycin). Within 4 months the primary and lung tumours had decreased substantially without evidence of progression at follow-up 5 months later. We conclude that IVP/IVA regimen is a potentially useful therapy when an osteosarcoma of the skull is in progression.
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  • 12
    ISSN: 1573-7373
    Keywords: medulloblastoma ; brain neoplasm ; chemotherapy ; ACNU ; vincristine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A favorable case of recurrent medulloblastoma, in which 19 years has elapsed with combination therapy due to surgery, radiation and chemotherapy since the initial operation, is reported. The case was a male of age 12 who was admitted due to medulloblastoma of the classical type. Tumor recurrences were observed 3 times within 7 years after the initial operation and radiation treatment. At the 3rd recurrence, a large tumor was found in the cerebellar vermis and left cerebellar hemisphere on CT with CSF dissemination and a high NSE level in the CSF (62 ng/ml). Only chemotherapy by intravenous administration of 2 courses of 120–150 mg ACNU (1.7–2.2 mg/kg) and 4 mg vincristine (0.06 mg/kg) with intrathecal administration of methotrexate was given at this time. The tumor image and gait disturbance with radicular pain disappeared completely and the NSE level in the CSF improved to within the normal range (5.4 ng/ml). The patient continues in complete remission, with a Karnovsky performance status of 100% at 4 years after the 3rd recurrence. We report full details of this case in which active treatments consisting mainly of chemotherapy proved to be effective for recurrent medulloblastoma, even though its prognosis is generally very unfavorable.
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  • 13
    ISSN: 1573-7373
    Keywords: high-grade astrocytoma ; chemotherapy ; children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Purpose This study was undertaken to evaluate the radiographie response to two cycles of chemotherapy prior to irradiation in newly diagnosed children with high-grade astrocytomas.Patients and methods. One hundred and thirty children less than 21 years of age with newly-diagnosed highgrade astrocytoma were treated with the ‘eight-drugs-in-one-day’ chemotherapy regimen as part of a phase III multi-institutional Childrens Cancer Group (CCG) trial. Computerized Tomographic (CT) or Magnetic Resonance Image (MRI) scans, obtained after two cycles of chemotherapy had been administered, were compared with post-operative scans to determine treatment response. Scans were evaluated by institutional radiologists, and were reviewed centrally by a single neuroradiologist. Results Of 79 patients with evaluable post-operative residual tumor on CT or MRI scans, 26 (33%) were determined on institutional evaluation to have had an objective response. However, central review of scans documented responses on only 14/79 (18%). A significantly higher response rate on central review was observed for those children 36 months of age or less at study entry than for older children (33% v 11%; p 〈 0.001). However, a higher disease progression rate was also observed for those children 36 months of age or less than for older children (21% v 2.6%; p 〈 0.001). Conclusion In this study, the largest yet reported in newly-diagnosed children with high-grade astrocytomas, the chemotherapy regimen has activity in younger children. The differences in response rates reported by institutional and central review highlight the difficulties inherent in assessing response to brain tumor therapy. However, the study does demonstrate the consistent ability of radiologists to identify disease progression within the institutional and central reviews.
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  • 14
    ISSN: 1573-7373
    Keywords: ependymoma ; ependymal cells ; estramustine-binding protein ; immunohistochemistry ; estramustine ; chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The mainstays of primary treatment of ependymoma are aggressive surgery followed by radiotherapy. Although spreading occasionally occurs in the cerebrospinal pathways, chemotherapy is still not established and no ultimate drug has so far been found. Estramustine-phosphate (EMP), with a demonstrated effect on astrocytomain vitro, has been shown to penetrate the blood-tumor barrier and to accumulate in human brain tumor tissue including ependymoma. It has been proposed that the cytotoxic effect of EMP depends on the presence of a binding protein, estramustine-binding protein (EMBP). In the present paper we have, for the first time, immunohistochemically demonstrated an EMBP-like protein in a series of ependymomas. Immunoreactivity was found within the cytoplasm of the tumor cells with a tendency to increase with increasing malignancy of the tumor. In addition, the occurence of EMBP-like protein was demonstrated in human ependymal cells. In the rat brain, a weak immunoreactivity was detected in early fetal neuroepithelial cells while the staining intensity was increased in mature ependymal cells in late fetal, neonatal, and adult rat. Thus, immunoreactivity for an EMBP-like protein was demonstrated in ependymoma tissue, normal human ependyma and in the developing rat ependymal cells.
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  • 15
    ISSN: 1573-7373
    Keywords: glioblastoma ; brain tumor ; radiation therapy ; chemotherapy ; ACNU
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We analyzed our treatment results of 71 operated patients with cerebral glioblastoma treated by conventional external radiation therapy (mean dose 60.2 Gy) combined with radiosensitizing agents. More than 50% reduction of tumor volume was obtained in 20 patients (28.2%). A response rate of at least 40% was obtained in patients treated with combined ACNU-vincristine-nicardipine, ACNU-5FU-hydroxyurea, or cisplatin alone. The combination of ACNU and vincristine with or without nicardipine resulted in significantly longer survival. The median survival in this group was 101.1 weeks and the two-year survival rate was 45.9%; these results were significantly better than those achieved with other ACNU combinations or other combinations without ACNU. In the analysis of survival, factors correlated to longer survival were a patient age of younger than 45 years, wide resection of the tumor, a good postoperative performance status (KS ≥70%), a radiation dose of 68–72 Gy, small postoperative tumor remnants (〈 20 cm3), no visible tumor after radiation therapy, and the administration of adjuvant chemotherapy. Maximum resection of the tumor and localized irradiation with a dose of 70 Gy combined with ACNU and vincristine appears to be the most effective treatment at present.
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  • 16
    Electronic Resource
    Electronic Resource
    Springer
    Journal of neuro-oncology 20 (1994), S. 103-109 
    ISSN: 1573-7373
    Keywords: rat brain tumor ; radiotherapy ; chemotherapy ; interaction ; drug delivery
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The rat 9L gliosarcoma brain tumor model has been used for more than thirty years to investigate a variety of potential therapeutic agents, combinations, schedules, and approaches that might be applicable to the management of high-grade malignant brain tumors in man. When tumor cells are implanted intracerebrally, a solid tumor grows until its mass results in the death of the animal, typically between 20 and 30 days post-inoculation. Radiation therapy (either single or fractionated doses) is effective at prolonging survival in a dose-dependent manner. Numerous cancer chemotherapeutic agents, by a variety of doses, schedules, and routes of delivery, have demonstrated therapeutic efficacy in the 9L model. The combination of radiation and agents such as AZQ, BCNU, bleomycin, and cis-platinum has resulted in prolongation of survival that is significantly better than either agent used alone, without exceeding the tolerance of critical normal tissues. These pre-clinical data suggest that combining standard fractionated radiation therapy with appropriate concomitant cytotoxic chemotherapeutic agents might benefit patients with high-grade brain tumors.
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  • 17
    Electronic Resource
    Electronic Resource
    Springer
    Journal of neuro-oncology 20 (1994), S. 177-185 
    ISSN: 1573-7373
    Keywords: brain lymphoma ; chemotherapy ; survival ; prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
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  • 18
    Electronic Resource
    Electronic Resource
    Springer
    Journal of neuro-oncology 20 (1994), S. 121-139 
    ISSN: 1573-7373
    Keywords: tissue concentrations ; brain tumors ; chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract There is general agreement that most chemotherapy agents achieve only relatively low concentrations in the normal central nervous system, that the blood-brain barrier is variably disrupted in malignant brain tumors, and that the concentration of chemotherapy drugs in the brain adjacent to tumor is intermediate between concentrations achieved in brain tumors vs normal brain. However, there is substantial controversy regarding the role of the blood-brain barrier in resistance to chemotherapy of intracerebral tumors. Many chemotherapy agents achieve concentrations in brain tumors that are comparable to those in extracerebral tumors, and drugs that cross the intact blood-brain barrier only poorly may be active against intracerebral tumors. Furthermore, the hypothesis that the brain is a pharmacological sanctuary where metastases may grow while tumor is responding in other parts of the body may be flawed: there are only 2 or 3 types of malignancies (out of all those that are sensitive to chemotherapy) in which the risk of isolated central nervous system relapse is moderately high, and even in these 2 or 3, effective central nervous system prophylaxis has minimal or no impact on overall survival. Furthermore, drugs that cross the BBB do not appear to be more effective than other drugs at reducing the risk of brain metastases, and brain metastases at the time of diagnosis do not necessarily convey a worse prognosis than metastases to various other sites. While average drug concentrations in brain adjacent to tumor are lower than those within brain tumors, very small numbers of tumor cells may be capable of inducing local leakiness in blood vessels, and there is little information on drug concentrations achieved in individual tumor cells within the brain adjacent to tumor. Furthermore, any limitation of uptake of drugs into brain tumors could be at least partially due to increased tissue pressure within tumors rather than being due to blood-brain barrier phenomena. This distinction could be important, since strategies that one might use to increase drug delivery to brain tumors might differ depending on whether the reduced delivery were due to barrier phenomena vs blood flow phenomena. The role of the blood-brain barrier in resistance of intracerebral tumors to chemotherapy remains unclear: while it may well play some role (and perhaps even a major one), self-fulfilling prophecies and unintentional bias in data selection and interpretation may have previously made it appear more important than it actually is. The feeling by many investigators that the blood-brain barrier is a major factor in brain tumor resistance to chemotherapy may at times have unnecessarily delayed and limited the exploration of new chemotherapy drugs and strategies in the treatment of human brain tumors. While antineoplastic drug pharmacology is important in the treatment of all malignant tumors, intrinsic drug cytotoxicity may well be a much more important factor in treatment outcome than is any limitation of drug uptake by the blood-brain barrier.
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  • 19
    ISSN: 1573-7373
    Keywords: extent of surgical resection ; tumor location ; glioblastoma multiforme ; radiation therapy ; chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Between 1988 and 1991, eighty-six patients with glioblastoma multiforme were evaluated in order to define the influence of extent of surgery and tumor location on treatment outcome. Patients underwent surgery followed by postoperative hyperfractionated radiotherapy and chemotherapy delivered according to one of two consecutive protocols. Surgery consisted of biopsy in 25 (29%) patients and subtotal or gross total tumor resection in 61 (71%) patients. Frontally located tumors were noted in 26 (30%) patients and other tumor locations were noted in 60 (70%) patients. Patients having more radical surgery had longer median survival time (MST) and higher 1- and 2-year survival rates than those with biopsy only (56 vs 29 weeks, respectively; 62 % and 23 % vs 16% and 0%, respectively; p=0.00000). Patients having frontally located tumors had longer MST and higher 1- and 2-year survival rates than those with other tumor locations (101 vs 47 weeks, respectively; 76% and 44% vs 37% and 2.5%, respectively; p=0.00001). Multivariate analysis confirmed that extent of surgery and tumor location were independent prognostic factors in patients with glioblastoma multiforme. Regarding progression-free survival, patients having more radical surgery had longer median time to tumor progression (MTP) than those with biopsy only (33 weeks vs 21 weeks, respectively). Also, progression-free survival at 1 year was higher in radically resected group than in biopsy only group (20% vs 0%, respectively; p=0.00000). Patients with frontally located tumors had longer MTP (42 weeks) and higher progression-free survival at 1 year (42%) than those with other tumor location (28 weeks and 1.7%, respectively; p=0.00002). Multivariate analysis confirmed that the extent of surgery and tumor location are independent prognosticators in patients with glioblastoma multiforme treated with combined modality approach using progression-free survival as an endpoint.
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  • 20
    Electronic Resource
    Electronic Resource
    Springer
    Breast cancer research and treatment 29 (1994), S. 127-138 
    ISSN: 1573-7217
    Keywords: EGF receptor ; monoclonal antibodies ; clinical trials ; humanized antibodies ; chemotherapy ; imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The epidermal growth factor (EGF) receptor and its ligands have an important regulatory role in breast carcinoma. We have produced a series of monoclonal antibodies (MAbs) directed against the external portion of the EGF receptor. These MAbs prevent the binding of the ligands to the receptor, block ligand-induced activation of the receptor, and can inhibit the growth of breast cancer cells both in tissue culture and in human tumor xenografts in nude mice. We have also shown that anti-EGF receptor antibodies greatly enhance the antitumor effects of chemotherapeutic agents active in breast cancer. Phase I clinical trials with single doses of MAb conducted in patients with tumors over-expressing EGF receptors demonstrated favorable pharmacokinetics, good tumor imaging, and a lack of toxicity. A human:murine chimeric antibody has been produced with comparable affinity and antitumor activity that will enable us to administer repeated doses of MAb either alone or in combination with chemotherapy. Our pre-clinical data support the concept that the EGF receptor may be an optimal target for treatment with receptor blocking antibodies, either alone or in combination with chemotherapy.
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  • 21
    ISSN: 1573-7217
    Keywords: breast cancer ; doxorubicin ; chemotherapy ; ifosfamide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Ifosfamide has single agent activity in advanced breast cancer and may potentiate the activity of doxorubicin. The combination of ifosfamide 5 g/m2 and doxorubicin 40 mg/m2 every 3 weeks for 4 cycles was used to treat 77 patients with advanced breast cancer. Fifty three patients had not received prior chemotherapy. All patients had one or more poor prognostic features, including tumor expression of epidermal growth factor receptor in 11/12 tested. The overall response rate was 74% (95% confidence intervals 62%-83%). The median survival was 9.4 months. The principal toxicities were febrile neutropenia and ifosfamide encephalopathy each in 6% of patients. A high percentage of the projected dose intensity was administered. This is a highly active combination with acceptable toxicity in advanced breast cancer, although the long term survival remains poor. Further exploration of ifosfamide in combination chemotherapy for advanced breast cancer is warranted.
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  • 22
    ISSN: 1573-7276
    Keywords: cerebral metastasis ; chemotherapy ; sanctuary site ; testicular cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Isolated central nervous system relapse in patients treated successfully with cisplatin-based chemotherapy for testicular cancer has been described infrequently. In a retrospective analysis we identified this complication in six of 417 patients. Five of the six patients had advanced pulmonary dissemination at onset of chemotherapy, and post-chemotherapy surgery did not reveal viable tumour tissue in any of these cases. All six patients developed a single cerebral metastasis during complete remission a median four months after discontinuation of chemotherapy. Five patients were treated with surgery and subsequent radio-therapy, one patient with irradiation alone. Three patients are alive relapse-free 19, 62 and 86 months after diagnosis of cerebral relapse. One patient was alive with cerebral disease for 12 months without evidence of systemic recurrence. Our data demonstrate that the brain may act as a sanctuary site in chemotherapy-treated testicular cancer. A review of the literature shows that an isolated cerebral relapse is an extremely rare complication, but carries a relatively favourable prognosis.
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  • 23
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    Investigational new drugs 12 (1994), S. 1-13 
    ISSN: 1573-0646
    Keywords: multidrug resistance ; p-glycoprotein ; chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Resistance to chemotherapy is the single most important reason for treatment failure in cancer patients. Over the past 15 years, we have gained significant insight into one of the mechanisms responsible for this process: multidrug resistance (MDR). Far from being a phenomenon limited to the laboratory, multidrug resistance has been identified in a wide variety of newly diagnosed and recurrent human tumors. A number of compounds can block p-glycoprotein and overcome MDRin vitro andin vivo. Current strategies to block MDR are discussed in this review. Future research in this area will focus on the identification of more selective and potent MDR reversing agents and the development of entirely new approaches to overcoming multidrug resistance such as monoclonal antibodies, immunotoxins, and gene therapy.
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  • 24
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    Journal of behavioral medicine 17 (1994), S. 41-55 
    ISSN: 1573-3521
    Keywords: coping ; cancer ; affect ; chemotherapy ; physical symptoms
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Psychology
    Notes: Abstract Relations among coping, physical symptoms, and affect were investigated in 43 women undergoing adjuvant chemotherapy for breast cancer. Patients were assessed at the same point in their treatment so that the time for which coping was reported would be equivalent across individuals. Patients were asked how they coped specifically with chemotherapy, rather than how they coped with cancer in general, to make the domain specific. Positive and negative affect were assessed separately, using a scale free of somatic content. Relations between coping and affect were consistent with prior studies that have employed a general approach to assessing coping. Coping correlates of positive and negative mood differed. When the relations between physical symptoms and affect were examined, physical symptoms were related to negative affect but not to positive affect. Findings are discussed in terms of their implications for coping with cancer as well as their implications for the general coping literature.
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  • 25
    ISSN: 1436-2813
    Keywords: early gastric carcinoma ; chemotherapy ; preoperative chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In order to achieve a complete prognosis for early gastric carcinoma, a greater effort must be made to improve its present treatment, considering the small percentage of patients who still die from recurrence despite the prompt initiation of surgery. Over the past 9 years, 26 patients with early gastric carcinoma have undergone surgical resection after receiving preoperative chemotherapy in the form of oral 5-FU or 5′-DFUR in our institute. The effectiveness of preoperative chemotherapy was evaluated by histopathological examination of the resected stomachs. Of a total of 24 patients with depressed type gastric cancer, 19 were histologically found to have a cancerless area within the cancerous lesion, 8 of whom were classified as being over Grade 1b. Gross changes were observed in 13 of these 24 patients. The frequency of multiple early gastric cancer occurring in patients who had not received chemotherapy was 11.6%, whereas in those who had received chemotherapy it was 3.8%. The findings of this study thus indicate that preoperative chemotherapy is useful for reducing minute cancer foci and microscopic metastatic lesions.
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  • 26
    ISSN: 1436-2813
    Keywords: splenic angiosarcoma ; chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Angiosarcoma of the spleen is a rare disease, and the prognosis of this disease is extremely unfavorable. We herein review the case of a 45-year-old Japanese woman, who received a combined chemotherapy with cyclophosphamide, Adriamycin, vincristine, and prednisone after splenectomy and experienced a good response. The various types of chemotherapy for this disease are also discussed with references to the above case because no effective chemotherapeutic protocol for angiosarcomas has yet to be established.
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  • 27
    ISSN: 0942-0940
    Keywords: Germ cell tumour ; chemotherapy ; CDDP ; VP-16
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A co-operative study for patients with intracranial germ cell tumours was performed to analyze their prognosis and the effectiveness of Cisplatin/Etoposide (CDDP/VP-16) chemotherapy. A total of 46 patients; 30 primary and 16 recurrent cases were registered from 15 participating neurosurgical institutions in Japan. Based on histological criteria and tumour markers, they were classified into three groups; germinoma, germinoma with syncytiotro-phoblastic giant cell (STGC), and non-germinomatous malignant tumour. Sixteen patients were treated with CDDP/VP-16 chemotherapy alone and the other 30 patients were treated by a combination of surgery and/or radiation in addition to chemotherapy. Eleven out of 13 patients (85%) with germinoma showed a complete (n=10) or partial (n=1) response to CDDP/VP-16 chemotherapy even if their tumours were recurrent and there was evidence of CSF dissemination. For the germinoma with STGC and non-germinomatous malignant tumour, a high response rate; 100% for the former and 78% for the latter, could also be achieved in both the primary and the recurrent cases except in those cases of immature teratoma. Their survival times were still different between them. Two-year survival was 50% in germinoma with STGC and 48% in non-germinoma, while it was 88% in germinoma cases.
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  • 28
    ISSN: 1573-3521
    Keywords: anxiety ; blood pressure ; chemotherapy ; distraction ; nausea ; relaxation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Psychology
    Notes: Abstract Sixty cancer chemotherapy patients were randomly assigned to one of six conditions formed by a 3(cognitive distraction, relaxation training, no intervention)×2(high anxiety, low anxiety) factorial design. All patients were followed for five consecutive chemotherapy sessions. Outcome measures included patient reports, nurse observations, and physiological indices. Results indicated that distraction patients reported less nausea prior to chemotherapy and lower systolic blood pressures after chemotherapy than controls. Relaxation training patients reported less nausea prior to chemotherapy and exhibited lower systolic and diastolic blood pressures after chemotherapy than control patients. There were no significant differences between distraction and relaxation training patients on any measure. Patients with high initial levels of anxiety exhibited continually elevated levels of distress throughout the chemotherapy experience; however, anxiety level did not interact with the effectiveness of the treatment interventions. Overall, the data support the use of both cognitive distraction and relaxation training for reducing the distress of chemotherapy with both high and low-anxiety patients and suggest that at least some of the effects of relaxation training can be achieved with distraction alone.
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  • 29
    ISSN: 1573-0646
    Keywords: 6-thioguanine ; phase II ; small cell lung cancer ; chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Nineteen eligible patients with recurrent small cell lung cancer were treated with a 120 hour continuous infusion of 6-thioquanine at a starting dose of 35 mg/m2/day. There were no responses in these 19 patients. Toxicity was acceptable with the primary toxicity being hematologic. Based on this trial, 6-thioquanine is not felt to have significant antitumor activity in this patient population.
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  • 30
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    Investigational new drugs 11 (1993), S. 161-168 
    ISSN: 1573-0646
    Keywords: transgenic mice ; chemotherapy ; mammary carcinoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Transgenic female mice carrying the V-Ha-ras transgene linked to the MMTV promoter, which developed mammary carcinomas, were treated with selected cancer chemotherapy drugs. Agents were administered i.p. on a daily × 9 schedule when mice developed tumors that were 50–100 mg in size. Drugs which are clinically effective against breast cancer were quite efficacious in the transgenic model at their maximum tolerated dose. Doxorubicin produced excellent responses in tumor-bearing transgenic mice, with several mammary carcinomas undergoing tumor shrinkage. Two anthrapyrazoles, DuP 937 and DuP 941, novel anticancer drugs with phase 2 activity against breast cancer, were as effective as doxorubicin in the oncomice. Mitoxantrone, a synthetic agent with some properties similar to the anthracyclines, also had antitumor activity, but not as pronounced as obtained with doxorubicin or the anthrapyrazoles. Cisplatin, a drug with limited use in human breast cancer, only caused modest antitumor responses. A computerized data analysis method based on the area under the tumor growth curve was developed to better quantitate the data and provide statistical information. This quantitative analysis confirmed the high statistical significance of the activity of doxorubicin or the anthrapyrazoles in the ras transgenic model, and defined an excellent dose response relationship for each drug tested. Our results suggest that the ras transgenic model may be useful for identifying drugs that have efficacy for breast cancer in women.
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  • 31
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    Journal of neuro-oncology 15 (1993), S. 157-163 
    ISSN: 1573-7373
    Keywords: neonatal brain tumors ; medulloblastoma ; radiation ; surgery ; chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A 9-day-old female presented with a large infra- and supratentorial medulloblastoma was treated by surgery, irradiation and chemotherapy. The infant suffered from vomit a few days after birth. She was hospitalized shortly thereafter, when head enlargement was noted. A CT scan taken on admission disclosed a large mass lesion in the cerebellum, extending to the pineal portion, and marked hydrocephalus. At the age of 14 days, the patient underwent ventriculoperitoneal shunting. When she was 67 days old, the tumor was radically resected. The histopathological diagnosis was medulloblastoma. Post operatively, she was irradiated with 30 Gy to the whole brain and 20 Gy to the tumor site. As chemotherapy, ACNU, 1-(4-amino-2-methyl-5-pyrimidinyl-3-(2-chloroethyl)-3-nitrosourea 1mg/kg was administered twice per 6 weeks. On discharge at 7 months, her only neurological deficit was nystagmus. One week later, she could not move her legs and was readmitted. A CT scan showed no intracranial changes, but the spinal cord was swollen at Th12-L5 level. Myelography demonstrated a filling defect at the L3-5 level. Following irradiation of the spinal cord, the paraparesis gradually improved. However, her general status was deteriorating and a follow up CT scan revealed recurrence of the intracranial tumor. The patient died at the age of 9.3 months which is longer survival time than previous reported one. Neonatal brain tumors are rare, and there have been only 24 cases of neonatal medulloblastoma. The prognosis for these patients is extremely poor, regardless of treatment. Surgery, radiation and chemotherapy for neonatal medulloblastoma are discussed.
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  • 32
    ISSN: 1573-7373
    Keywords: glioblastoma ; tumor metabolism ; positron emission tomography ; chemotherapy ; prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Sequential positron emission tomographic scans with [18F]-2-fluorodeoxyglucose (PET-FDG) were performed on 6 patients with glioblastoma multiforme who were treated with adjuvant BCNU. Scans were acquired before and 24 hours after BCNU. All patients had prior brain irradiation. Ratios between the maximal tumor FDG uptake and the contralateral white matter FDG uptake, the glucose uptake ratio, were determined. Percent changes in the glucose uptake ratio between the baseline scan and the 24 hour post-treatment scan were of prognostic significance. Patients with the largest percent changes in FDG uptake had the shortest survival. In contrast, neither the baseline glucose uptake ratio nor the visual tumor grade accurately predicted length of survival.
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  • 33
    ISSN: 1573-7373
    Keywords: MCNU ; experimental brain tumor ; intracarotid infusion ; streaming phenomenon ; chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We observed the tissue delivery of a novel water-soluble nitrosourea, 1-(2-chloroethyl)-3-(methyl-α-D-glucopyranos-6-yl)-1-nitrosourea (MCNU) in rats bearing experimental brain tumors by conducting autoradiography on all. Prior to this study, the development of a streaming phenomenon was ascertained (and thus finding the optimum velocity for intra-arterial infusion) by14C-iodoantipyrine (IAP) autoradiography. Furthermore, a single pass extraction value of MCNU was measured. At an arterial infusion rate of 0.2 ml/min., the streaming phenomenon was recognized but the tracer was fairly evenly distributed at a rate of 1.0 ml/min. On the other hand, the single pass extraction value for MCNU was 0.18 ± 0.036 (mean ±S.D., n=3, under pentobarbital anesthesia). It was suggested that MCNU is very unlikely to be transported into the normal rat brain. We conducted14C-MCNU autoradiography to observe tissue distribution of MCNU following its intra-arterial and intravenous infusions in a brain tumor model using rats. The normal side (the side where no infusions were given) and the cerebral cortex at the side affected by the tumor (the side where the infusion was given) showed hardly any uptake of14C-MCNU in both the intra-arterial and intravenous infusion groups. The tumorous section was divided into the periphery and the center to measure tissue concentration of the tracer in each section. Compared against the cortical section, the periphery and the center showed significant increases in the concentration (approximately 11 to 15 times and 3 to 7 times, respectively, the figure for the cortical region) for both the intra-arterial and intravenous groups. When compared against the intravenous infusion group, the arterial infusion group showed a significantly high rate of accumulation (1.3 to 3.9 times).
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  • 34
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    Journal of neuro-oncology 15 (1993), S. 133-139 
    ISSN: 1573-7373
    Keywords: recurrent brainstem glioma ; VP-16 ; chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract 12 patients: (7 males and 5 females) with recurrent brainstem gliomas were treated with the oral topoisomerase inhibitor VP-16 (Etoposide). Patients ranged in age from 3 to 49 years with a median age of 7 years. All patients had been previously treated with radiation therapy (conventional fractionation: 4; hyperfractionation: 8) and 5 had received prior nitrosourea-based chemotherapy at time of tumor recurrence. Tumor recurrence was documented by radiographic tumor enlargement utilizing brain MRI with gadolinium enhancement (12) and clinical neurologic deterioration (9). Two patients underwent biopsy pathologically documenting tumor recurrence. Each cycle of therapy consisted of 21 days of VP-16 (50 mg/m2/day) followed by a 14 day rest followed by an additional 21 days of VP-16 (50mg/m2 day). Complete blood counts were followed bi-weekly and a neurologic examination and brain MRI scan with contrast were performed prior to initiation of each cycle of therapy. Treatment related complications included: partial alopecia (5); diarrhea (5); weight loss (4); neutropenia (2); and thrombocytopenia (4). No patient required transfusion or antibiotic treatment of neutropenic fever. There were no treatment related deaths. 12 patients were evaluable of whom 6 demonstrated a radiographic response (1 complete; 3 partial; 2 stable disease) with a median duration of response of 8 months. In summary; oral VP-16 is a well tolerated and relatively non-toxic chemotherapeutic agent with apparent activity in this small cohort of patients with recurrent brainstem gliomas.
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  • 35
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    Journal of neuro-oncology 15 (1993), S. 185-193 
    ISSN: 1573-7373
    Keywords: chemotherapy ; malignant glioma ; brain metastasis ; blood-brain barrier ; mannitol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To assess whether therapeutic efficacy is related to the intra-arterial (IA) mannitol infusion prior to ACNU and cisplatin (CDDP) for malignant brain tumors, the survival time of patients with and without mannitol infusion was compared. Ninety-eight patients were randomly assigned to either a mannitol infusion group (group A) or a non-mannitol infusion group (group B); 34 with malignant gliomas (18 in group A and 16 in group B) and 64 with brain metastases (36 in group A and 28 in group B). During radiotherapy, ACNU and CDDP at a dose of 100mg/body were given through the common carotid artery at a rate of 20mg/min. In group A, 50ml of 20% mannitol was injected intra-arterially at a rate of 50ml/min immediately prior to the injection of chemotherapeutic agents. Of the patients with malignant gliomas, the median survival time (MST) was 52 weeks for all 34 cases, 68 weeks for group A, and 47 weeks for group B. Survival analysis showed no significant differences between the two treatment groups. Of the patients with brain metastases, the MST was 40 weeks for all 64 cases, 47 weeks for group A, and 24 weeks for group B; the survival time was significantly longer in group A as compared to group B (p〈 0.05). This study has demonstrated that, for the patients with brain metastases, IA mannitol infusion provided a survival benefit in the IA chemotherapy employing ACNU and CDDP. In contrast, IA mannitol infusion offered no survival benefit to the patients with malignant gliomas.
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  • 36
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    Journal of neuro-oncology 17 (1993), S. 123-129 
    ISSN: 1573-7373
    Keywords: metallothionein ; brain tumor ; chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Metallothioneins (MTs) are intracellular proteins containing the highest amount of thiol groups within the cytoplasm. These thiol groups are able to bind several cytotoxic agents, such as platinum compounds and alkylating agents. Increased levels of MT are one mechanism of resistance to these anticancer drugs, as intracytoplasmic binding of MT prevents the active molecules from reaching their target, the intranuclear DNA of tumor cells. MT synthesis can easily be induced by physiologic heavy metals such as zinc and copper. Pharmacological modulation of MT levels has been used to increase the MT pool in normal tissues and decrease their susceptibility to the toxicity of anticancer drugs. In the case of tumors arising in the brain, where the inducibility of MT synthesis is low, this approach would allow protection of normal tissues without decreasing the antitumor activity of the cytotoxic agents. The interaction of MT with cytotoxic agents is not limited to covalent binding. A correlation between MT synthesis and amplification of oncogenes such asras has been reported. Furthermore, the cytotoxic drugs are bound by MT after competition with zinc and copper; these metals are cofactors of numerous metalloenzymes, some of which are involved in the metabolism of nucleic acids. Competitive displacement of these metals might modify nucleic acid metabolism and influence cellular proliferation. On the other hand, increased MT levels could provide a zinc cofactor reserve that increases the cell's reparative potential when faced by DNA damage by cytotoxic agents. Although the physiologic role of MT in resistance to the cytotoxic effects of anticancer drugs remains unclear, a better understanding of the interaction between MT and chemotherapeutic agents may be important in the treatment of cancer.
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  • 37
    ISSN: 1573-7373
    Keywords: experimental brain tumor ; capillary permeability ; blood brain barrier ; chemotherapy ; brain injury
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Experimental brain tumors were excised from rats for sequential observation of changes in local capillary permeability during the postsurgical period. Experimental brain tumor-bearing rats were prepared by stereotaxic transplantation of cultured tumor cells and the resultant tumor was delineated by administration of a dye. Following excision of the stained tumor by craniotomy, sequential changes in local capillary permeability were quantitatively followed-up by autoradiography, using14C-amino-isobutyric acid as a tracer. Capillary permeability was enhanced following surgery, reaching a maximum both in the extent and degree on the third day. After undergoing a gradual reduction, it showed a marked increase for the second time in a very small area on the 10th postoperative day. A recurrence of the tumor was responsible for this late but marked increase. For a control group, the caudate nucleus was excised from normal rats, followed by observation of the sequential changes in the local capillary permeability. Due to surgical procedure, capillary permeability reached a maximum both in the extent and degree on the 5th postoperative day (slightly later than in the tumor group). This change in capillary permeability was less pronounced than in the tumor group. The difference in the conditions of surgery — tumor excision and partial excision of a normal brain tissue — appeared to explain this difference. The results of this study indicated that it is more desirable to give water-soluble antineoplastic agents early during the postoperative period for chemotherapy of a malignant brain tumor after surgery.
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  • 38
    ISSN: 1573-7373
    Keywords: chemotherapy ; intraarterial ; brain tumors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Sixteen patients with intracerebral tumors received intraarterial cisplatin, teniposide, and BCNU combined with intravenous cisplatin, teniposide, and cytosine arabinoside. Oral glycerol and intravenous mannitol were given along with the intravenous chemotherapy in an attempt to increase drug delivery to tumor by augmenting tumor blood flow. Thirteen additional patients were treated with the same regimen, but received all the chemotherapy intravenously. Of the 16 patients receiving intraarterial chemotherapy (median survival, 14 weeks), none responded, 5 (31%) were stable for 〉 8 weeks, 8 (50%) failed, and 3 (19%) were unevaluable due to early death. Of the 13 patients receiving all their treatment intravenously (median survival, 13 weeks), 3 (23%) responded, 1 (8%) was stable, 7 (54%) failed, and 2 (15%) were unevaluable due to early death. In the patients receiving intraarterial chemotherapy, toxicity included ipsilateral retinal toxicity (2 patients), ocular pain or headache (10), periorbital swelling and flushing (6), increased brain edema with focal neurological deficits and drowsiness (5), and catheter-related carotid artery thrombosis followed by fatal herniation (1). Myelosuppression was worse in patients who received all their treatment intravenously than in those receiving intraarterial chemotherapy (p 〈 0.05). Neutropenic sepsis developed in 4 patients on the intraarterial arm (1 fatal) and in 5 patients on the intravenous arm (2 fatal). Other toxic effects were similar whether or not patients received intraarterial treatment or only intravenous treatment. Overall, toxicity of this regimen was excessive, and response rates were lower than would have been expected with single agent therapy.
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  • 39
    ISSN: 1573-7217
    Keywords: breast cancer ; chemotherapy ; dose-intensity ; inflammatory breast cancer ; locally advanced breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Up to 15% of women with breast cancer have locally advanced disease at diagnosis. The poor response of these patients to local therapy alone and the frequent development of disseminated disease suggest that early intensive systemic therapy may benefit these women. Twenty-four patients with non-metastatic, locally advanced, primarily inflammatory, inoperable breast cancer were treated with a 16-week dose-intense chemotherapy regimen as induction therapy. Treatment consisted of 8 repetitive 2-week cycles consisting of 100 mg/m2 cyclophosphamide orally D1-7, 40 mg/m2 doxorubicin intravenously (IV) D1, 1 mg vincristine IV D1, 100 mg/m2 methotrexate IV D1, 10 mg/m2 leucovorin every 6 hours for six oral doses D2-3, and 600 mg/m2 5-FU IV over 2 hours D2. A continuous infusion of 300 mg/m2 5-FU per day was given IV D8-9 of each 2-week cycle. After induction all patients had at least a partial clinical response and were operable; 9/24 (37%) achieved a clinical complete response. All patients underwent at least a simple mastectomy. Pathologic examination revealed no evidence of gross macroscopic tumor in 11/24 patients (46%) and no evidence of microscopic disease in 4/24 patients (17%). Seven of 24 patients (29%) had no microscopic disease in the breast. At a median follow-up of 45 months, there have been 10 relapses in the 24 patients treated with this induction regimen. The actuarial relapse-free survival at 5 years is 58%. Actuarial overall survival at 5 years is 75%. We conclude that this regimen is safe and well-tolerated and that the results of this therapy are sufficiently promising to warrant further study of this regimen in patients with locally advanced breast cancer.
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  • 40
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    Breast cancer research and treatment 26 (1993), S. 267-274 
    ISSN: 1573-7217
    Keywords: breast cancer ; chemotherapy ; metastasis ; multidrug resistance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Expression of mdr1 gene has been evaluated in 34 tumor samples obtained from breast cancer patients who were classified according to their treatment, and clinical follow-up. No gene amplification was found. mdr1-RNA was never detected in 29 primary breast tumors including 5 samples from patients previously treated by 6 courses of 5-fluorouracil, epirubicin, cyclophosphamide (FEC). On the other hand, mdr1-RNA expression was detected in 1 local recurrence and 2 out of 3 metastases, all of them being treated and exhibiting a poor evolution. A second, untreated local recurrence remained negative. Clinical follow-up for 7 to 48 months in patients receiving chemotherapy showed that absence of mdr1-RNA could not be an accurate factor of satisfactory response to chemotherapy. But, all the patients with detectable mdr1-RNA exhibited a poor evolution and response to treatment. In conclusion, evaluation of mdr1-RNA seemed to be of little interest in primary breast tumors. However, the concomitant presence of an mdr1-RNA and a metastatic phenotype could give a new insight into the relationship between invasive and resistance properties of cancer cells. Such situations would need to be analyzed very carefully for a better utilization of chemotherapy.
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  • 41
    ISSN: 1573-7217
    Keywords: adoptive immunotherapy ; breast cancer ; chemotherapy ; interleukin-2 ; OK-432 ; pleural effusion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Sixty-seven breast cancer patients with cytologically-confirmed malignant pleural effusion, who required intrapleural treatment, were analyzed retrospectively. The patients received their first thoracentesis between 1980 and 1990. Among them, 29 patients received intrapleural administration of OK-432, a streptococcal preparation, followed by the transfer of autologous pleural effusion lymphocytes cultured with interleukin-2. Other intrapleural treatments consisted of OK-432 alone (12 patients), chemotherapeutic agents alone (n = 9), a combination of OK-432 and chemotherapy (n = 16), or others (n = 1). Twenty-six of the 29 patients given OK-432 plus cultured effusion lymphocytes responded, while only 15 of the 38 patients who received other treatments did (p 〈 0.01). Median survival time and 5-year survival rate of patients who received OK-432 and cultured lymphocytes was 12 months and 36%, while those of the patients who received other treatments was 3 months and 0%, a significant (p〈 0.001) difference in survival. Multivariate analysis using Cox's proportional hazard model revealed that the treatment (adoptive immunotherapy) was the most significant (p 〈 0.005) factor to prolong the survival of the patients among several prognostic factors. Thus, OK-432 and adoptive immunotherapy is a promising therapy that should be further evaluated in a prospective study.
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  • 42
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    Plant cell, tissue and organ culture 32 (1993), S. 303-309 
    ISSN: 1573-5044
    Keywords: chemotherapy ; ELISA ; eradication ; orchid ; ribavirin ; odontoglossum ringspot virus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Odontoglossum Ringspot Virus has been eradicated from Cymbidium Sw. through chemotherapy based on incorporation of ribavirin (VIRAZOLE®) into the in vitro culture medium of protocorms. Applications of the virustatic agent for several consecutive subcultures freed protocorms of the virus. Acclimated plantlets regenerated from those protocorms are healthy as determinated by enzyme-linked immunosorbent assay (ELISA). No resurgence of virus occurred over a period of 5 years. Besides, trueness to type was total at flowering level and the batch grown was perfectly homogeneous. To secure fast and effective eradication of the virus during the consecutive subcultures of protocorms with ribavirin, three factors proved to be of prime importance: accurate isolation of new growths from initial tissues, VIRAZOLE® concentration and frequency of transplanting in new media.
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  • 43
    ISSN: 1573-2568
    Keywords: fulminant hepatic failure ; hepatitis B virus carrier ; chemotherapy ; interferon ; cyclosporin A ; immune response
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A 56-year-old female HB carrier developed fulminant hepatic failure with propagation of precore mutant hepatitis B virus following two sessions of intensive chemotherapy for non-Hodgkin's lymphoma. She was treated with interferon and cyclosporin A for the suppression of viral replication and enhanced host immune responses. She recovered from liver failure with histological evidence of marked regenerative activity. She again developed fulminant hepatic failure with reactivation of the hepatitis B virus following repeated chemotherapy for recurrent non-Hodgkin's lymphoma. This case report supports the view that both enhanced viral replication and host immune responses contribute to the development of fulminant hepatitis in HB carriers. Treatment suppressing both mechanisms may be effective in this type of fulminant hepatitis.
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  • 44
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    Digestive diseases and sciences 38 (1993), S. 923-926 
    ISSN: 1573-2568
    Keywords: Barrett's esophagus ; columnar-lined esophagus ; chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Columnar-lined or Barrett's esophagus is a premalignant condition. It is almost unvariably due to chronic gastroesophageal reflux. Since there are some reports that Barrett's esophagus can be induced by chemotherapy, we investigated 20 male patients, treated with chemotherapy for testicular cancer, and 18 female patients, treated with high-dose chemotherapy for breast cancer. Only one patient in the testicular cancer group had Barrett's esophagus of the circumferential type, in addition to typical reflux esophagitis and a hiatal hernia four years after chemotherapy. In the breast cancer group one patient had an indeterminate junction. Our results do not support the hypothesis that chemotherapy poses a substantially increased risk for the development of Barrett's esophagus.
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  • 45
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    Biotherapy 6 (1993), S. 291-302 
    ISSN: 1573-8280
    Keywords: P-glycoprotein ; mdr1 ; multidrug resistance ; gene therapy ; myelosuppression ; chemotherapy ; bone marrow transplantation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Drug-induced myelosuppression is a frequent reason for curtailing chemotherapy in cancer patients. ‘Rescue’ of myelosuppressed patients with autologous marrow transplants is reasonably advanced and permits an increase in the dose of anticancer drugs. Despite this improvement, patients often relapse with drug resistance disease. The human multidrug resistance (mdr1) gene might make it possible to render hemopoietic stem cells resistant to anticancer drugs after transfer of this gene. By introducing resistant stem cells into patients it might be possible to treat these patients repeatedly with otherwise ablative therapy. This review explores the feasibility ofmdr1 gene therapy.
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  • 46
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    European journal of nutrition 31 (1992), S. 110-120 
    ISSN: 1436-6215
    Keywords: Antioxidanzien ; Vitamine ; Chemotherapie ; Strahlentherapie ; künstliche Ernährung ; Antioxidants ; vitamins ; chemotherapy ; radiotherapy ; clinical nutrition
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Medicine
    Description / Table of Contents: Summary Plasma from 22 patients was examined for alpha- and gamma-tocopherol (vitamin E), the carotinoids beta-carotene (provitamin A) and lycopene, retinol (vitamin A), and ascorbic acid (vitamin C) before, during and after conditioning chemotherapy for bone marrow transplantation, 18 of these received total body irradiation as well. In addition, alpha-tocopherol in red blood cell membranes was measured. Retinol and ascorbic acid have been applied in multiple of the recommended doses (Deutsche Gesellschaft für Ernährung and Recommended Dietary Allowance, respectively). The chosen doses were sufficient to maintain the initial plasma concentrations of these vitamins. However, alpha-tocopherol (in RDA doses) and beta-carotene (no RDA established) concentrations deteriorated after the conditioning therapy (20 and 50% loss, respectively). The loss of these lipidsoluble antioxidants has been considered to result from lipid peroxidation. On the basis of the presented results we propose intervention studies to investigate the effect of high dose antioxidant administration on the toxicity (mainly of liver and lung) of intensive antineoplastic therapy protocols.
    Notes: Zusammenfassung Bei insgesamt 22 Patienten, die sich einer intensiven Chemotherapie vor Knochenmarktransplantation (KMT) unterzogen, davon bei 18 Patienten in Kombination mit einer Ganzkörperbestrahlung, wurden alpha- und gamma-Tocopherol (Vitamin E), die Karotinoide beta-Karotin (Provitamin A) und Lycopin, weiterhin Retinol (Vitamin A) und Ascorbinsäure (Vitamin C) im Plasma bestimmt. Ergänzend wurde der alpha-Tocopherolgehalt von Erythrozytenmembranen gemessen. Während Retinol und Ascorbinsäure mit dem Mehrfachen der empfohlenen Dosis (Deutsche Gesellschaft für Ernährung bzw. Recommended Dietary Allowance) appliziert wurde und dadurch die initialen Plasmakonzentrationen dieser Substanzen gehalten werden konnten, stellte die empfohlene alpha-Tocopheroldosis keine ausreichende Substitution dar. beta-Karotin nahm unter der Konditionierungstherapie vor KMT ebenso wie alpha-Tocopherol ab, wobei für die Zufuhr von beta-Karotin bisher keine Empfehlungen vorliegen. Der Verlust der fettlöslichen Antioxidanzien alpha-Tocopherol und beta-Karotin während der einwöchigen Konditionierungstherapie um 20 bzw. 50% ist wahrscheinlich auf eine gesteigerte, therapieassoziierte Lipidperoxidation zurückzuführen. Den Befunden kommt in bezug auf Nebenwirkungen der antineoplastischen Therapie besonders an Leber und Lunge Bedeutung zu, bei denen ursächlich freie Radikale in der Pathophysiologie beteiligt sind.
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  • 47
    ISSN: 0942-0940
    Keywords: Brain tumour ; chemotherapy ; induced hypertension ; xenon-enhanced CT
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Changes in tumour blood flow under an induced hypertensive state were examined in malignant brain tumours to know if the precondition for the effectiveness of induced hypertensive chemotherapy — relative increase in tumour blood flow — are fulfilled. Tumour blood flow was measured under both a resting and an induced hypertensive state in 12 patients with various malignant brain tumours (6 gliomas, 6 metastatic brain tumours) using xenon-enhanced computed tomography. The blood pressure was elevated 40% above the systemic blood pressure of the resting state by the infusion of angiotensin II. Tumour blood flow increased 30% on average above the normal brain tissue blood flow after the induction of an induced hypertensive state (p 〈 0.05). The tumour blood flow increased in 11 cases of malignant tumours, but decreased in one case with massive brain oedema after induced hypertension. The increase in blood flow was higher in hypervascular tumours and less in hypovascular tumours. Therefore, induced hypertensive chemotherapy probably will be more effective in hypervascular malignant brain tumours with small mass effects.
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  • 48
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    Acta neurochirurgica 116 (1992), S. 137-146 
    ISSN: 0942-0940
    Keywords: Posterior third ventricle tumours ; pineal tumours ; management ; operative indication ; technique ; chemotherapy ; results
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The evaluation of tumours located in the posterior part of the third ventricle or pineal region is achieved best by magnet resonance imaging (MRI). It shows the exact localization and extent, the involvement of neighbouring structures like thalamus or quadrigeminal plate and the displacement of the large veins, the internal cerebral veins, the vein of Galen and the veins of Rosenthal. If only CT is available, angiography shoud be performed prior to operation to identify the course of the veins. In children with a pineal region tumour the “tumour markers” AFP and β-HCG should be determined before operation. We approach the rare tumours entirely located within the posterior part of the third ventricle by the posterior interhemispheric transcallosal route with the patient in prone position with the head elevated. The same approach is used for pineal region tumours extending above the internal cerebral veins. Tumours arising from the posterior thalamus extending into the thalamus and ventricle as well, are better approached by the posterior transcortical transventricular route since the lateral view is rather limited by the midline approach. The most frequent tumours in the pineal region are approached if they are located below the internal veins by the infratentorial, supracerebellar route in the sitting position. A total of 60 cases are evaluted. If AFP and/or β-HCG are positive a highly malignant nongerminomatous germ-cell tumour must be suspected. We recommend initial chemotherapy with a combination of Vinblastine, Ifosfamide and Cis-platin without biopsy to avoid tumour seeding. After the “markers” are normalized operative removal of the residual tumour and radiotherapy should be carried out. In a series of 13 children operated on for pineal region tumours a rigid neuropsychological and endocrine evaluation was perfomed with encouraging results. During the last 10 years we have performed 49 open operations and 11 stereotactic biopsies. 40% of the patients were children under the age of 18. 40% of the tumours in childhood and 60% in adults were benign. In childhood 24% were germinomas and 20% non-germinomatous germ cell tumours. The indications for stereotactic biopsy and for open operation after biobsy are discussed.
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  • 49
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    European journal of clinical pharmacology 43 (1992), S. 329-339 
    ISSN: 1432-1041
    Keywords: 6-Mercaptopurine ; Acute lymphoblastic leukaemia ; 6-thioguanine nucleotides ; cytotoxicity ; chemotherapy ; immunosuppression ; azathioprine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
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  • 50
    ISSN: 1573-0646
    Keywords: hexamethylmelamine ovarian cancer ; chemotherapy ; ovarian cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract A Phase II trial of an intravenous preparation of Hexamethylmelamine was performed in ovarian cancer. Patients who had received prior Platinum based chemotherapy and had measurable disease were eligible. Among 15 evaluable patients, there were no objective responses. Two patients did show clinical and laboratory evidence of improvement. Toxicity was predominantly nausea and vomiting with minimal other toxicity. This intravenous form of Hexamethylmelamine has not shown meaningful activity in ovarian cancer patients who have failed prior platinum treatment.
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  • 51
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    Investigational new drugs 10 (1992), S. 347-349 
    ISSN: 1573-0646
    Keywords: merbarone ; sarcoma ; soft tissue ; chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Thirty-seven patients with advanced soft tissue sarcoma were treated with merbarone utilizing a daily intravenous schedule for five days. Only one partial response was observed in the thirty-three evaluable patients. The major toxicities were renal, with elevation of creatinine and/or proteinuria, and gastrointestinal, with mild to moderate nausea and vomiting. Merbarone in this dose and schedule has minimal activity in soft tissue sarcoma.
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  • 52
    ISSN: 1573-7373
    Keywords: germ cell tumors ; cisplatin ; chemotherapy ; pineal tumor ; brain neoplasm
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We report a retrospective review of our experience with cisplatin-based chemotherapy in eight patients (ages 9–44 years) with histologically confirmed primary central nervous system germ cell tumors. Five patients received chemotherapy as the primary treatment, radiation therapy being administered either at completion of chemotherapy or between chemotherapy courses. Three patients received cisplatin-based chemotherapy for recurrent disease after prior radiation therapy and/or surgery. Four of five patients treated with chemotherapy at diagnosis are in complete remission at 11–14 months from diagnosis. The remaining patient twice achieved complete remission prior to dying of progressive disease 16 months after diagnosis. Two of three patients treated with chemotherapy for recurrent disease are in complete remission at 20 and 26 months; the remaining patient deteriorated after the first cycle of chemotherapy and expired six months thereafter. Overall, of seven patients evaluable for response, five achieved complete remission with chemotherapy alone, and two with chemotherapy and radiation therapy. Our results confirm previous reports of high complete remission rates utilizing cisplatin-based chemotherapy in conjunction with radiation therapy. Prospective evaluation of cisplatin-based chemotherapy followed by radiation therapy is warranted.
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  • 53
    ISSN: 1573-7373
    Keywords: malignant glioma ; chemotherapy ; blood-brain barrier ; brain tumor survival
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In the past, chemotherapeutic treatment of patients with high grade malignant gliomas following surgery and radiation has not added significantly to the 12–14 month median survival rate. Over four years, 37 patients with high grade malignant gliomas underwent 246 treatment procedures with a combination of methotrexate, cyclophosphamide, and procarbazine given in association with hyperosmolar mannitol-induced transient breakdown of the blood-brain barrier. These patients have demonstrated a median survivorship of 22 months after considering age, Karnofsky Performance Score, and necrosis by the Cox Proportional Hazards model. The study group had a mean age of 43 years, and mean Karnofsky Performance Score of 67%. Sixty-five percent of the procedures had well-documented barrier disruption. Sixteen percent remained in complete remission while 24 patients (65%) had partial or temporary remission. Progression-free intervals after blood-brain barrier disruption/chemotherapy ranged from 1–47 (mean 15) months. Neurotoxicity has been minimal with one peri-procedural mortality and five patients suffering an increase in neurologic deficit after a procedure. The results of this study are consistent with and further extend the reported literature on this method of brain tumor therapy as described in other centers. Chemotherapy in conjunction with osmotic disruption of the blood-brain barrier may provide the pharmacokinetic advantage sufficient to significantly improve survival in patients with high grade malignant glioma.
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  • 54
    ISSN: 1573-7373
    Keywords: choroid plexus carcinoma ; chemotherapy ; brain tumors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Choroid plexus carcinoma (CPC) arising in the infant poses several treatment dilemmas. The tumor is often not totally resectable at presentation given its large size and tendency to invade adjacent brain. Because of its predisposition to regrow and metastasize, some form of postoperative cytotoxic therapy is required. Chemotherapy (CHT), as opposed to radiotherapy (RT), has 4 more desirable risk/benefit role in infants, since it is relatively sparing of late neurologic sequelae. Three young male children presented with large intraventricular CPC at 9, 18, and 27 months of age. One child had subarachnoid metastases at diagnosis and the other two had localized disease. Subtotal resections were accomplished and all three required VP shunts. Initial CHT consisted of four monthly courses of cisplatin (20 mg/m2) and etoposide (100 mg/m2), both administered intravenously, daily, for five days. After four courses, two children had complete responses and one had stable disease. Additional CHT was given but one child developed 4 local recurrence and another diffuse CNS metastases. Both died with intratumoral hemorrhages at 5 and 57 months following diagnosis. The third child remains in continuous remission 46 months after diagnosis. None of the children received RT. Chemotherapy may permit long term deferral of RT. More aggressive CHT regimens should be explored in infants with CPC.
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  • 55
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    Journal of neuro-oncology 12 (1992), S. 85-91 
    ISSN: 1573-7373
    Keywords: pineal tumors ; surgery ; radiation therapy ; chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract From 1972–1985, 30 patients with pineal area tumor have been treated with combinations of surgery and irradiation, no patient receiving chemotherapy as a primary recommendation. Patients ranged between 3 and 69 years of age, 18 were male and 12 female. In 18 patients a tissue diagnosis was made initially, 14 patients required shunts before definitive management and in 8 of the 14 tissue diagnosis was made at the same time. Eight patients had no surgical intervention at any time. Patients who have received irradiation have had whole brain irradiation, local field irradiation, or craniospinal irradiation. Two elderly patients died rapidly of their malignant processes before definitive treatment could be given. Only one patient with a non neoplastic lesion was seen. This was a bleed from an AVM with no underlying tumor. One patient with a pineocytoma was not irradiated. Overall, two-thirds of our patients are alive 5 to 15 years after treatment. There has been no surgical mortality and minimal morbidity from biopsy. Late effects of treatment include one patient with mild hearing loss and three patients with endocrinopathies amenable to medical treatment. We believe that tissue diagnosis allows optimal field design and dose recommendations to be made by the radiotherapist in addition to defining prognosis. In our experience, endodermal sinus tumor and pineoblastoma are highly malignant, and in view of their poor prognosis with conventional management consideration of more radical treatment with a possible role for chemotherapy is suggested.
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  • 56
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    Journal of neuro-oncology 12 (1992), S. 131-135 
    ISSN: 1573-7373
    Keywords: malignant gliomas ; chemotherapy ; carmustine ; cisplatin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Forty-five patients with malignant gliomas were treated after aggressive surgical resection with alternating intravenous carmustine and cisplatin both during and after radiation therapy. Thirty-three patients were considered evaluable for responses, 17 had glioblastoma multiforme (GBM),14 had anaplastic astrocytoma (AA) and 2 had anaplastic oligodendroglioma (AO). The median age of the evaluable patients was 47 years. The median time to tumor progression was 34.5 weeks, and the median survival for the entire group was 76 weeks. Early progression occurred more frequently in patients with glioblastoma than in those with AA or AO. Seventeen patients (55%) were alive at 18 months (6 GBM, 9 AA, 2 AO). Toxicity was mainly hematologic, otic and tolerable. The results suggest that further trial is warranted to assess the efficacy of alternating carmustine and cisplatin in conjunction with radiation therapy postoperatively in patients with malignant gliomas.
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  • 57
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    Journal of neuro-oncology 12 (1992), S. 153-158 
    ISSN: 1573-7373
    Keywords: chemotherapy ; recurrent glioma ; ‘eight-in-one day’
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Thirty-five adult recurrent GBM patients, divided randomly in two groups of 19 and 16 cases, had been treated with two regimens of chemotherapy: a) ‘eight-drugs-in-one-day’; b) procarbazine + CCNU + vincristine (PCV) respectively. Chemotherapy was planned at the tumor relapse and delivered as long as tolerated without irreversible sequelae or until the CT scan showed tumor progression. Multiple agents are used simultaneously in the therapeutic approach using ‘eight-in-one’ to kill as many heterogeneous cells of malignant glial tumor as possible and minimize the emergence of cellular resistance to chemotherapy. Rate response to chemotherapy and the median adjunctive survival time (6.5 and 6 months, respectively) are not significantly different in the two arms of this study. Our experience with such an aggressive multi-drugs combination ‘eight-in-one-day’ was disappointing if compared with less toxic, better tolerated and easy delivered (PCV) regimen.
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  • 58
    ISSN: 1573-7373
    Keywords: malignant glioma ; glioblastoma ; brain tumors ; astrocytoma ; cisplatin ; chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Twenty-one patients with recurrent malignant glioma who had failed prior chemotherapy with nitrosoureas were treated with high-dose intravenous cisplatin on days 1 and 8 of successive 4 week cycles. Fourteen patients were evaluable for response. Four patients showed partial responses; mean time to tumor progression (MTP) was 8 weeks. Six patients stabilized; MTP was 11 weeks. Four patients showed no response. There were no infectious or hemorrhagic complications, but partial hearing loss occurred in 7 patients and severe vomiting in 8 patients. High-dose intravenous cisplatin demonstrates substantial activity against malignant gliomas recurrent after chloroethylnitrosourea (CENU) failure.
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  • 59
    ISSN: 1573-7373
    Keywords: low-grade astrocytoma ; chemotherapy ; vincristine ; etoposide ; tumors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Twenty patients, aged 6 months to 20 years, with low-grade astrocytoma (LGA) participated in a chemotherapy trial of vincristine (VCR) and etoposide (VP-16). Fourteen children had recurrent progressive disease at entry on study. Prior treatment consisted of surgical resection alone (6), surgical resection and irradiation (4), surgical resection, irradiation and chemotherapy (2), surgery and chemotherapy (1), and irradiation and chemotherapy (1). Six patients were treated at initial diagnosis of LGA because they were less than 5 years old (5) or for a second primary tumor (1). Four recurrent patients and 3 newly diagnosed patients underwent surgical debulking of their tumors immediately prior to study entry. Tumors were located in the optic nerve/chiasm/hypothalamus (8), brain stem/cerebellum (4), cerebral hemispheres (3), midline structures (3), and spinal cord (2). The treatment plan administered in an out-patient setting consisted of weekly VCR 1.5 mg/m2 for 7 to 8 weeks and VP-16100 mg/m2 for 5 days repeated every 6 weeks for a total of 18 months of therapy. Responses were evaluated by computerized tomography or magnetic resonance imaging. Of the 20 patients, l exhibited a partial response maintained for 12+ months, 3 exhibited minor responses maintained for a period of 10+ to 35 months, and 11 maintained stable disease for 10 to 42 months. Of the 11 patients with stable disease, 2 were withdrawn early from the study without further therapy. Five of the 20 patients developed progressive disease; for 4 of these 5, this occurred during the first course of therapy. Subsequently, these 5 died due to tumor. Vincristine and etoposide produced minimal hematological and neurological toxicity and appeared to offer some benefit in patients with LGA. The authors suggest the therapy potentially can produce prolonged disease stabilization, or perhaps help avoid irradiation in the young child with LGA.
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  • 60
    ISSN: 1573-7373
    Keywords: interleukin 1 ; malignant brain tumor ; myelosuppression ; ACNU ; chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of recombinant human interleukin 1 β (rHuIL-1 β) on myelosuppression induced by 3-[(4-amino-2-methyl-5-pyrimidynyl)methyl]-1-(2-chloroethyl)-1-nitrosourea hydrochloride (ACNU) was studied. In in vivo study using BALB/c mice, pretreatment with 1 µ g/mouse of rHuIL-1 β as a single intraperitoneal (i.p.) injection had a significant preventive effect on thrombocytopenia as well as granulocytopenia induced by ACNU at an intravenous dose of 60 mg/kg. Facilitated recovery by rHuIL-1 β administered seven days after injection of high-dose ACNU was also observed. Experimental combination immunochemotherapy with high-dose ACNU and rHuIL-1 β was performed in nude mice inoculated with human glioblastoma subcutaneously. The elongation of the survival time of the tumor bearing nude mice was also observed in combined use of high dose ACNU with rHuIL-1 β. Seven patients with malignant brain tumors received intravenous 2.5-3 mg/kg ACNU. All patients were subcutaneously injected with 2 × 104-U or more rHuIL-1 β twice a week or daily. The mean nadir of leukocyte, granulocyte, and thrombocyte counts of the 7 patients received 2.5-3 mg/kg ACNU were significantly higher than in matched historical controls. In combination with rHuIL-1 β, it may be possible to use chemotherapeutic agents at a relatively high dose.
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  • 61
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    Veterinary research communications 16 (1992), S. 293-300 
    ISSN: 1573-7446
    Keywords: apramycin ; blood ; chemotherapy ; chickens ; goats ; kanamycin ; pharmacokinetics ; pigeons ; rabbits ; sheep
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Comparative studies on some selected pharmacokinetic parameters for kanamycin in sheep, goats, rabbits, chickens and pigeons, and for apramycin in sheep, rabbits, chickens and pigeons were carried out after intravenous administration of the two drugs at a dose of 10 mg/kg. The results revealed that a two-compartment open model was most suitable for kanamycin, while for apramycin a one-compartment open model was usually optimal. The log distribution rate constant (α) of kanamycin was significantly correlated to the log of the body mass (r=0.919,n=5,p〈0.05). Interspecies differences in the apparent volume of distribution (Vda) of kanamycin were small. These differences were larger for apramycin, as were the variations in the area under the serum concentration-time curve (AUC) and in the total body clearance (ClB) of both kanamycin and apramycin, both having almost a threefold difference depending on the species but without any correlation to body mass. The values of the log half-life of kanamycin in the mammals in this study and also those from data in the literature revealed a significant correlation with log body mass between animal species according to the equation: $$t_{{\raise0.5ex\hbox{$\scriptstyle 1$}\kern-0.1em/\kern-0.15em\lower0.25ex\hbox{$\scriptstyle 2$}}\beta } = 38.47W^{0.21} (r = 0.7648,n - 10,p〈 0.05)$$ .
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  • 62
    ISSN: 1573-7217
    Keywords: chemotherapy ; HER2/c-erbB-2/neu ; MCF-7 ; resistance ; tamoxifen ; transfection
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Since the poor prognosis associated with HER2 amplified breast cancers might be explained by a mechanistic association between p185HER2 overexpression and therapeutic resistance, we assessed the chemo-endocrine sensitivity of estrogen receptor (ER) containing MCF-7 breast cancer cells transfected with full-length HER2 cDNA. Of the 36 isolated MCF/HER2 subclones, 7 were found to overexpress p185HER2 surface receptor at levels 3 to 45-fold greater than parental or control transfected cells (MCF/neo). The overexpressing transfectants possessed increased inositol-1,4,5-trisphosphate-3'-kinase activity comparable to enzyme activity in the endogenously HER2 amplified breast cancer cell lines SK-Br-3 and BT-474. The anti-p185HER2 monoclonal antibody and receptor-specific partial agonist, muMAb4D5 (4D5), known to inhibit growth of SK-Br-3 and BT-474 cells, produced no significant growth inhibitory effect on any of the transfectants including the 45-fold overexpressing MCF/HER2–18 cells which were studied in greater detail. MCF/HER2–18 cells contained at least partially functioning exogenous receptor since 4D5 (3µg/ml) specifically stimulated phosphorylation of p185HER2 and its co-precipitating ptyr56 substrate within 5 min, and this was followed at 1 h by a transient induction ofc-myc but notc-fos mRNA. ER content and thein vitro sensitivity of MCF/HER2–18 cells to 5-fluorouracil and adriamycin were identical to those of control transfectants and parental cells. However, these highly overexpressing transfectants had acquired low level (2 to 4-fold) resistance to cisplatin and were no longer sensitive to the antiestrogen tamoxifen (TAM). To compare the hormone-dependent tumorigenicity of the HER2 transfectants, MCF/HER2–18 and control cells (MCF, MCF/neo-3) were implanted into ovariectomized athymic nude mice. No tumors were produced in the absence of estradiol (E2) administration. In E2 supplemented mice, MCF/HER2–18 tumors grew most rapidly. When E2 treatment was stopped and daily TAM injections were initiated, MCF-7 and MCF/neo-3 tumor growth ceased immediately, while MCF/HER2–18 tumors continued to show an accelerated growth rate lasting weeks. This pattern of hormone-dependent, TAM-resistant growth exhibited by the MCF/HER2–18 tumors in nude mice supports the possibility that p185HER2 overexpression in human breast cancers may be linked to therapeutic resistance.
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  • 63
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    Breast cancer research and treatment 21 (1992), S. 27-34 
    ISSN: 1573-7217
    Keywords: breast cancer ; chemotherapy ; combination ; dose intensification ; new drugs ; outpatient treatment ; quality of life ; single agents
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The treatment of advanced breast cancer has undergone relatively little change in the past decade. Reasons for such a static situation are the sobering realization that even effective chemotherapeutic regimens have had a minor impact on survival, and the paucity of new effective agents that have been introduced since initial combination treatments. Based in part on this lack of progress, in recent yearsdose-intensification in search of a curative strategy has been widely adopted. Its role remains to be defined, but ultimately it is likely to be relegated to situations where tumor burdens have been effectively reduced. This reduction in burden may not currently be feasible in many advanced presentations. Outpatient efforts will therefore focus on the following: 1) employing single agents optimally (e.g. infusion 5-fluorouracil), 2) using regimens which integrate new drugs with activity (e.g. taxol), and 3) testing measures which may improve the quality of life (e.g. bisphosphonates in the presence of bone metastases). Although one cannot approach the treatment of advanced breast cancer with the (misplaced) optimism of two decades ago, the expanded armamentarium currently available should lead to a more rational application of chemotherapy. Treatments will increasingly be based on the biology of the cancer, and on the therapeutic index and action of the drugs.
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  • 64
    ISSN: 1573-7217
    Keywords: breast cancer ; chemotherapy ; doxorubicin ; mitoxantrone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Weekly low dose mitoxantrone (3 mg/m2) plus doxorubicin (8 mg/m2) was administered as second-line chemotherapy to 33 patients with advanced breast cancer. Four out of 28 evaluable patients (14%) obtained a partial response with a median duration of 34 weeks (range 18–67+ weeks), while 8 patients (29%) showed stable disease with a median duration of 28 weeks (range 11+–60 weeks). Gastrointestinal toxicity and alopecia were mild. Grade II and III leukopenia occurred in 63% of the courses without serious infectious disease. Four patients experienced an asymptomatic drop of 16–20% in the left ventricular ejection fraction (LVEF) after relatively low cumulative doses of each drug, and one patient with a history of pericarditis carcinomatosa and mediastinal irradiation developed a heart failure. In conclusion, this second-line combination treatment had moderate activity in breast cancer and caused only few subjective side effects, especially with respect to gastrointestinal symptoms.
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  • 65
    ISSN: 1573-5044
    Keywords: chemotherapy ; elimination ; meristems ; ornithogalum ; virus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Virus-indexed Ornithogalum ev. Rojel plants were produced by eliminating Ornithogalum mosaic virus (OMV) through meristem-tip culture. The best plantlet regeneration was obtained from meristems derived from adventitious buds which developed on leaf explants taken from mother plants at the flowering stage. Acyclovir had no effect as an anti-viral compound on plantlet regeneration or virus elimination. Adenine arabinoside retarded plantlet development at concentrations of 10 mg l-1 and higher, while 5.0 mg l-1 suppressed the virus concentration beneath a detectable level in young plants. All the mature plants, however, tested positively for the presence of OMV.
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  • 66
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    Neurological sciences 13 (1992), S. 717-722 
    ISSN: 1590-3478
    Keywords: Glioblastoma ; chemotherapy ; platinum
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Sommario Scopo di questo studio è stato quello di verificare la tollerabilità ed efficacia di alcuni differenti protocolli chemioterapici. Ai fini dello studio sono stati trattati 84 Pazienti affetti da glioblastoma e valutati il Time to tumor progression e Survival Time. I Pazienti sono stati divisi in quattro differenti gruppi terapeutici: a) BCNU b) CDDP+VP-16 c) CBDCA+BCNU e) CBDCA+VP-16+BCNU. A 18 mesi oltre la metà dei pazienti trattati con schemi contenenti platino derivati sono sopravvissuti, con un Survival time significativamente più lungo rispetto a quello dei pazienti trattati con solo BCNU. Le differenze tra i vari gruppi del Time to tumor progression non sono risultate invece statisticamente significative.
    Notes: Abstract The aim of this study was to verify the tolerability and efficacy of therapeutic chemotherapy protocols, employing different combinations of cis-platin, carbo-platin, etoposide and carmustine in primary glioblastoma patients. The purpose was focused on 2 end points: the response index to treatment, the TTP (tumor progression) and the ST (survival time). Eighty-four out of a group of 99 consecutive glioblastoma patients, entered this study. Patients were divided into 4 disparate treatment groups: (A) BCNU alone; (B) CDDP+VP-16; (C) CBDCA+BCNU; (D) CBDCA+BCNU+VP-16. The effectiveness and the TTP of the protocols differed, but differences were not statistically significant. Data concerning platinum treatment compare favorably with the best literature results. At 18 months more than half the carboplatin-treated patients are alive. Moreover these patients had a significantly longer ST than those treated with BCNU. We conclude that platinum-based chemotherapy has a beneficial effect on glial tumors.
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  • 67
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    Neurological sciences 13 (1992), S. 311-315 
    ISSN: 1590-3478
    Keywords: Cisplatin ; peripheral nerve diseases ; chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Sommario Trentotto soggetti portatori di tumori cerebrali della serie gliale sono stati trattati con 5 cicli mensili di cisplatino, ciascuno di 135 mg/m2, per via endovenosa. Segni e sintomi di neuropatia periferica sono stati valutati clinicamente ed elettrofisiologicamente. Il nostro approccio differisce dai precedenti lavori riportati in letteratura in quanto offre due importanti vantaggi: i tumori cerebrali primitivi non causano mai neuropatie paraneoplastiche; non è stato usato nessun altro farmaco neurotossico all'infuori del cisplatino. Lo studio conferma l'esistenza della neuropatia periferica indotta dal cisplatino anche in questo modello altamente specifico. Abbiamo potuto osservare chiari segni clinici di neuropatia periferica nell'80% dei pazienti trattati con una dose cumulativa di cisplatino di 675 mg/m2. Dal punto di vista eletrofisiologico si è osservata una riduzione progressiva e dose-correlata nell'ampiezza dei SAP, espressione di una neuropatia sensitiva assonale e/o neuronale.
    Notes: Abstract 38 patients with glial brain tumors received 135 mg/m2 cisplatin intravenously every month for 5 courses. Signs and symptoms of peripheral neuropathy were evaluated clinically and electrophysiologically. This approach differs from methods previously reported in that it offers two major advantages: primary brain tumors do not cause paraneoplastic neuropathy; no neurotoxic drugs other than cisplatin were employed. Our study confirmed in this highly specific clinical model the existence of cisplatin peripheral neuropathy: we observed definite clinical signs or symptoms of neuropathy in 80% of patients receiving a cumulative cisplatin dosage of 675 mg/m2; there was a progressive dose-related decrease in SAP amplitudes, expression of a sensory axonopathy or neuronopathy.
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  • 68
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    Journal of Cellular Biochemistry 50 (1992), S. 128-131 
    ISSN: 0730-2312
    Keywords: bladder carcinoma ; chemoprevention ; chemotherapy ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: α-Interferon combined with 5-fluorouracil results in significant antitumoral activity im metastatic bladder carcinoma refractory to standard MVAC chemotherapy.As a single agent, α-interferon is ineffective for invasive ormetastatic diseasem, but appears to contribute to the increased response rate of patients with invasive chemotherapy-refractory disease. Although most patinets with superficial bladder carcinoma will not develop invasive disease, patients in complete remission from invasive disease are at high risk for relapse.In vitro assays indicate that fenretinide (4-HPR) line, α-interferon, and 5-fluorouracil posses significant antitumoral activity in human transitional cell carcinoma (TCC) lines. Some features of postchemotherapy-refractory TCC are similar to those of initial superficial disease (senhsitivity to biological therapy). The biological study of patients with residual postchemotherapy disease may permit the development of strategies which will prevent the recurrence of malignancy within the bladder following an initial complete remission, in addition to developin strategies forthe selection and treatment of patients with high risk superficial disease. © 1992 Wiley-Liss, Inc.
    Additional Material: 1 Ill.
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  • 69
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    Digestive diseases and sciences 36 (1991), S. 1653-1656 
    ISSN: 1573-2568
    Keywords: primary adenocarcinoma ; duodenal bulb ; chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A 48-year-old man had primary adenocarcinoma of the duodenal bulb. The extensive hepatic metastasis of the patient did not allow any major surgical procedure. Therefore UFTM chemotherapy was performed and was associated with three years of improvement. Subjective symptoms were relieved and test findings indicated normalization of liver biochemistry as well as CEA and CA 19-9. X-ray, endoscopy, and pathological findings indicated the disappearance of the carcinoma of the duodenal bulb. In addition, both ultrasonic examination and CT of the abdomen showed marked reduction of the hepatic metastasis. The authors do not hesitate to recommend the UFTM therapy as a therapeutic modality for inoperable and metastatic primary adenocarcinoma of the duodenum.
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  • 70
    ISSN: 1573-0646
    Keywords: cisplatin ; etoposide ; melanoma ; chemotherapy ; phase II
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Fourteen patients with metastatic melanoma were treated with cisplatin and etoposide by bolus intravenous infusion daily for 5 consecutive days each month. All patients were evaluable for toxicity and twelve for response. Eight patients were treated with cisplatin 20 mg/m2 and etoposide 100 mg/m2 daily. Because of excessive myelosuppression, the daily dose of etoposide was reduced to 75 mg/m2 in the remaining six patients. There were no major responses among 12 evaluable patients (major response rate ≤ 24% with 95% confidence). The median time to progression was one month. One patient with a liver metastasis had a minor response lasting 6 + months. The combination of cisplatin and etoposide in these doses and schedule lacked sufficient clinical efficacy in the treatment of metastatic melanoma.
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  • 71
    ISSN: 1573-0646
    Keywords: mesothelioma ; dihydro-5-azacytidine ; chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
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  • 72
    ISSN: 1573-0646
    Keywords: endometrial cancer ; chemotherapy ; esorubicin ; cardiac toxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The Southwest Oncology Group conducted a phase II study of esorubicin treatment in patients with advanced endometrial cancer who had received no prior chemotherapy. Twenty of 31 patients were fully evaluable for response and toxicity. There were no clinical responses to treatment and 60% (12/20) of the patients developed severe or life threatening leukopenia on therapy. One evaluable patient was removed from study after a cumulative dose of 150 mg/M2 due to a reduction in left ventricular ejection fraction on MUGA scan and another developed congestive heart failure several months after discontinuation of treatment. Esorubicin has significant toxicity and limited clinical activity in patients with advanced endometrial cancer.
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  • 73
    ISSN: 1573-0646
    Keywords: biomodulator ; chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
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  • 74
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    Investigational new drugs 9 (1991), S. 79-82 
    ISSN: 1573-0646
    Keywords: phase II ; lymphoma ; menogaril ; chemotherapy ; low grade
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The NCI Canada Clinical Trials Group conducted a phase II study of menogaril given intravenously every 4 weeks in low-grade non-Hodgkin's lymphoma. Fifteen of 26 eligible patients had had no prior therapy. Partial responses were seen in 9 patients (35%). Toxicity was moderate including myelosuppression, nausea, phlebitis, alopecia, and lethargy. This drug has only modest activity in this potentially responsive group of patients.
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  • 75
    ISSN: 1573-7373
    Keywords: nitrosoureas ; glioma ; BCNU ; SarCNU ; PET ; chemotherapy ; brain tumor ; BBB
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary This paper describes the study of the pharmacodynamics of two 11C-labelled nitrosoureas, 1,3-bis-(2-chloroethyl) nitrosourea (BNCU) and sarcosinamide chloroethylnitrosourea (SarCNU), both labelled in the carbonyl position. Distribution of the radioactivity as measured by positron emission tomography was compared to the distribution of radioactivity observed after injection of 68Ga-EDTA, this being used as an indicator of the blood-brain barrier integrity around the brain tumor. Data suggest that the new nitrosourea, SarCNU, most likely enters brain tissue by different mechanism(s) than BCNU, which enters by diffusion. Data also indicate that use of SarCNU may result in a better tumor to brain ratio than BCNU.
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  • 76
    ISSN: 1573-7373
    Keywords: ifosfamide ; mesna ; astrocytoma ; recurrent ; chemotherapy ; brain neoplasms
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Sixteen patients who developed CT or MRI scan evidence of recurrent diffuse astrocytoma after radiation therapy and nitrosourea-containing chemotherapy received ifosfamide (2500 mg/m2/day for 3 consecutive days) and mesna (500 mg/m2/dose, 5 doses/day for 3 consecutive days). Toxicity consisted primarily of leukopenia in that 60 percent of patients developed leukocyte nadirs less than 1500/mcL. Excessive somnolence occurred in three patients and may have contributed to a case of fatal pneumonia in one patient but was reversible in the other two. No patient had CT or MRI scan evidence of tumor regression. One patient remains stable at 11.3+ months, but all other patients developed evidence of progressive disease less than 6 months from initiation of therapy. The median times to tumor progression and death were 2.0 and 4.8 months, respectively. In conclusion, while ifosfamide and mesna can be given safely at this dose and schedule, there is no evidence of antitumor effect. The degree of leukopenia observed likely would prevent further dose escalation of ifosfamide or addition of other myelosuppressive agents without additional means of bone marrow support in this population of patients.
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  • 77
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    Journal of neuro-oncology 10 (1991), S. 57-74 
    ISSN: 1573-7373
    Keywords: brain neoplasm ; chemotherapy ; drug delivery system ; intraneoplastic injection
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract An extensive effort to search for curative chemotherapeutic approaches has found no ‘breakthrough’ in management of patients with malignant brain tumors. Despite the trials with new agents or protocols of multiple agents, systemic chemotherapy has failed to provide reliable clinical response. Interstitial chemotherapy has been practiced for malignant brain tumors with administering chemotherapeutic compounds directly into the tumor which provide increased and prolonged drug concentration in the tumor, reduction of systemic toxicity and bypassing the blood-brain barrier. These theoretical advantages encourage further pursuing interstitial chemotherapy for patients with malignant brain tumors who would otherwise be always fatal. In this review, the literature has been reviewed to identify methods toxicity and efficacy of interstitial chemotherapy. Clinical and experimental data indicate limited toxicity and promising efficacy. Various methods to administer the agents were utilized; intraoperative topical application, local injections through catheters or implantable controlled drug delivery system. Selection of ideal chemotherapeutic agents and development of drug delivery system need further investigations.
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  • 78
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    Journal of neuro-oncology 10 (1991), S. 191-201 
    ISSN: 1573-7373
    Keywords: primary brain lymphoma ; radiation therapy ; chemotherapy ; AIDS
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Recommendations regarding the current therapy of primary brain lymphoma (NHL-CNS) take into account the occurrence of this tumor in immunocompetent and immumosuppressed hosts. Immunohistochemical evaluation of biopsy material or spinal fluid provides the diagnosis in 90% of patients. For the immunocompetent, pre-irradiation intra-venous or intra-arterial chemotherapy with Methotrexate alone or in combination with other agents is provided to treat tumor within multiple brain sites. Subarachnoid deposits are treated with Methotrexate by intrathecal administration. Radiation is provided after chemotherapy and for the treatment of vitreal/retinal deposits or symptomatic lesions within the spinal axis. The therapy of recurrent NHL-CNS makes use of intravenous Methotrexate or high dose Cytosine Arabinoside. Immunosuppressed patients respond to reduction of immunosuppressive medication. The therapy of NHL-CNS in the AIDS patient makes use of corticosteroids followed by cranial irradiation. A discussion of emerging trends in the therapy of NHL-CNS in the AIDS and non-AIDS population is provided.
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  • 79
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    Journal of neuro-oncology 10 (1991), S. 263-270 
    ISSN: 1573-7373
    Keywords: optic glioma ; chemotherapy ; brain neoplasm ; children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Two infants, ages 14 and 4 months, with extensive optic pathway tumors were treated with intensive chemotherapy called MADDOC: nitrogen mustard, doxorubicin, cis-platinum, dacarbazine, vincristine, and cyclophosphamide. The first child had hydrocephalus with an enhancing mass at the hypothalamus which followed the optic radiation to include the lateral geniculate body and medial temporal lobe. A v-p shunt was placed, and biopsy revealed a Grade 11 astrocytoma. One month later, the child developed malignant ascites. Intensive induction chemotherapy was then begun with cis-platinum 100 mg/m2 and cyclophosphamide 3 g/m2 for two initial cycles. The ascites resolved within one week, and chemotherapy was continued for 10 courses of the 6-drug MADDOC regimen. CT scans showed a gradual shrinkage of the tumor mass by approximately 70%. The enhancing areas continued to decrease in size through 20 months after completing MADDOC. The child has not received radiation and is well 4 years 7 months post diagnosis. The second infant had massive enlargement of the right optic nerve with an enhancing chiasmatic mass extending into the suprasellar space, hypothalamus, and brain stem. This infant was not biopsied; she also received induction MADDOC chemotherapy for 12 cycles. CT scans showed a definite decrease in the chiasmatic mass by the fifth cycle, with continued reduction by approximately 40% after 10 months. Twenty-three months from diagnosis there was asymptomatic evidence of tumor growth. The child is being treated with carboplatinum and remains ophthalmologically and radiographically stable 43 months from diagnosis.
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  • 80
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    Journal of neuro-oncology 11 (1991), S. 165-170 
    ISSN: 1573-7373
    Keywords: chemotherapy ; glioma ; cis-platin ; etoposide ; survival-time
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Thirty eight patients with malignant gliomas (27 GBM and 11 AA) were treated with up to 7 cycles of CDDP + VP16 every month after surgery. Chemotherapy was planned as two cycles before and 5 cycles after radiation (42 Gy) using a three times daily fractionation schedule. No severe toxicity was observed. The object of our study was to investigate the antitumor effectiveness by combining CDDP plus VP16 against primary malignant glial tumors. The time to tumor progression (TTP) and survival time (ST) of the GBM patients in the present study were 38.5 and 68,5 weeks respectively. The TTP of the AA patients was 73 weeks and the ST was not calculated as most patients are still alive. By the 18th. month after surgery, 38% of GBM and 74% of AA patients treated with (CDDP + VP16) are still alive. This study demonstrates that the combination of CDDP and VP16 is effective in patients with malignant gliomas.
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  • 81
    ISSN: 1573-7373
    Keywords: Brain tumor ; nitrosoureas ; neurotoxicity ; chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
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  • 82
    ISSN: 1573-7373
    Keywords: medulloblastoma ; c-myc ; neuronal ; glial ; chemotherapy ; radiotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Medulloblastoma is the most common central nervous system malignancy of childhood, with approximately 350 new cases seen in the United States each year. Although the low incidence of this tumor, compared with adult neoplasms such as breast or colon carcinoma, has limited laboratory and clinical research, recent studies have greatly enhanced our understanding of the biology, phenotype, genotype, and therapy of medulloblastoma. Further efforts to integrate laboratory and clinical studies of this tumor may allow design of novel therapeutic approaches resulting in enhanced disease-free survival.
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  • 83
    ISSN: 1573-7373
    Keywords: childhood brain tumor ; chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Sixteen patients with recurrent childhood brain tumors were treated with intravenous cisplatin, cytosine arabinoside and etoposide (PAE), daily for three days every three to four weeks. Objective responses were observed in 6 of 15 evaluable patients and an additional six patients had stable disease for 〉 6 months. The tumor-specific response rate for astrocytoma/glioma was 3 of 7 and for medulloblastoma was 2 of 4. The mean progression-free interval was 11.0 months and the hazard rate for progression was 0.085 per patient-month of observation. The most common toxicities were neutropenia and thrombocytopenia. Clinically significant ototoxicity wasidentified in 7 patients. The activity of PAE chemotherapy for recurrent childhood brain tumors warrants further investigation.
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    Cancer and metastasis reviews 10 (1991), S. 335-341 
    ISSN: 1573-7233
    Keywords: brain neoplasms ; metastasis ; chemotherapy ; and review
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Chemotherapy for brain metastases has been considered ineffective because the drugs do not penetrate the intact blood brain barrier. Alternate explanations for past failures of chemotherapy include observations that 1) many solid tumors which metastasize to brain are drug-resistant regardless of location, 2) brain metastases often occur following failure of primary chemotherapeutic regimens to control systemic metastases, and 3) previous trials of chemotherapy employed agents other than those known to be most effective against the primary malignancy. Furthermore, laboratory studies have demonstrated that cytoxic levels of many drugs can be measured in tumor tissue from primary and metastatic brain tumors. These clinical and pharmacologic observations suggest that chemotherapy would be expected to have limited value unless known effective combination regimens are employed as first-line therapy in chemosensitive malignancies. Recent reports of chemotherapy for patients with brain metastases from small cell lung carcinoma, gestational choriocarcinoma, germ cell malignancies, and breast carcinoma do describe response rates in the brain similar to those in other organ sites. In conclusion, chemotherapy for cerebral metastases can be expected to be effective only when effective drugs for systemic metastases are available. While the blood-brain barrier may be an additional detriment to successful treatment, other factors may be more important.
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  • 85
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    Breast cancer research and treatment 17 (1991), S. 171-177 
    ISSN: 1573-7217
    Keywords: adjuvant chemotherapy ; breast cancer ; chemotherapy ; combined modality treatment ; radiotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Thirty four patients treated with mastectomy and axillary node dissection for potentially curable breast cancer received a seven month combined adjuvant chemotherapy and radiation therapy program. These patients were considered to be at high risk for recurrence because they had either three or more positive axillary lymph nodes or their primary tumor was greater than 5 cm in diameter. The chemotherapy given at 3-week intervals consisted of cyclophosphamide, 600 mg/m2, Adriamycin 40mg/m2, and methotrexate 40 mg/m2 during cycles 1 through 3 and 7 through 9. Radiation therapy was administered during cycles 4 through 6 with concomitant administration of 5-fluorouracil 600 mg/m2, vincristine 1.4 mg/m2, and prednisone 40 mg/m2 for 7 days. Median follow up time from initiation of study is 60 months (range 36–93). Seventeen of 34 patients (50%) remain free of recurrent breast cancer. Distant metastases and local-regional recurrence have occurred in 16 (47%) and 4 (12%) patients, respectively. Significant myelosuppression and infections requiring hospitalization were seen in 4 patients, with 1 treatment-related death. Adriamycincontaining chemotherapy and post-operative radiotherapy can thus be combined in an adjuvant treatment program with acceptable toxicity.
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  • 86
    ISSN: 1573-7217
    Keywords: adjuvant treatment ; breast cancer ; chemotherapy ; immunotherapy ; radiotherapy ; randomized trial
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In this study, patients with operable breast cancer T2 or T3, treated by mastectomy + axillary dissection and with invaded axillary nodes (N+), were randomized to receive either: 1) postoperative locoregional and pelvic radiotherapy (RX) and Poly(A).Poly(U) (AU), 60 mg IV once a week for 6 weeks, or 2) CMF (cyclophosphamide 100 mg/sqm P.O. on days 1–14, methotrexate 40 mg/sqm IV on day 1 and 8, fluorouracil 600 mg/sqm IV on day 1 and 8; monthly cycle, for 6 months. Between March 1982 and December 1985, 517 patients were enrolled, 257 of whom were treated by RX + AU and 260 with CMF. The main clinical, pathological and prognostic characteristics were equally distributed in the two groups. The present analysis was conducted after a mean follow-up of 69 months (S.D.=13). There was no significant difference in overall survival (OS) between the two groups (test adjusted by center and menopausal status); the five-year OS rate was 74% in the RXAU group and 77% in the CMF group. Relapse-free survival (RFS) was significantly higher (p=0.05) in the RXAU group compared to the CMF group; the five-year RFS rates were 57% and 46% in the two groups respectively. This short, well-tolerated combined RXAU treatment appears to be as efficient as CMF and might offer an alternative to chemo- or hormonotherapy, in case of contraindications to these treatments.
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  • 87
    ISSN: 1573-7217
    Keywords: adjuvant therapy ; breast cancer ; chemotherapy ; node positive ; radiation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 158 evaluable patients with stage II, lymph node positive, carcinoma of the breast were randomized to adjuvant therapy with either melphalan (L-PAM) or cyclophosphamide, methotrexate, and fluorouracil (CMF) after mastectomy. In addition, patients were randomized to be treated with or without post-operative irradiation therapy (RT) in addition to their chemotherapy. At a median follow-up time of 11 years, there is no difference in time to relapse (P=0.69) or survival (P=0.55) among the four treatment groups. Multivariate analysis including treatment arm, age, race, tumor size, histologic type, performance status, time to onset of treatment, menopausal status, and number of positive nodes, revealed that only the number of positive nodes (〈4 vs ≥ 4) was related to disease-free and overall survival. Ten year relapse-free survival for patients with 〈4 positive nodes compared to those with ≥4 positive nodes was 63% versus 30%, and overall survival 63% versus 41%, respectively. Patients who received post-operative radiation therapy had significantly less local recurrence than those treated with chemotherapy alone (P=0.03) but without improvement in relapse-free or overall survival. In this trial, post-operative radiation therapy when added to chemotherapy decreased the risk of local recurrence without adverse effects on survival. Treatment outcome was not influenced by chemotherapy regimen, but differences may have been obscured by the small sample size.
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    Breast cancer research and treatment 20 (1991), S. 63-67 
    ISSN: 1573-7217
    Keywords: amonafide ; advanced breast cancer ; chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Twenty-eight patients with advanced breast cancer refractory to prior hormone and/or first-line chemotherapy (with or without anthracycline drugs) were treated with the investigational agent amonafide at a dose of 800 mg/m2 intravenously over 3 hours repeated every 4 weeks. Five objective tumour responses of 5.0 months' median duration were observed in the 20 patients without previous anthracycline exposure, including 1 CR. Leukopenia was the dose-limiting toxicity; though it was generally modest with the 800 mg/m2 amonafide starting dose, an initial dose reduction should be considered in patients with prior radiotherapy and/or bone marrow involvement. Other adverse reactions included nausea/vomiting (53%), phlebitis/erythema along the vein injected (7%), and mild neurotoxic symptoms during the drug administration such as headache, tinnitus, and diaphoresis (21%). Amonafide is an active compound for the treatment of patients with advanced breast cancer and should be considered for further evaluation and incorporation in combination chemotherapy.
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  • 89
    ISSN: 1573-7217
    Keywords: chemotherapy ; CMF-induced emesis ; ondansetron (GR 38032F) ; serotonin antagonist
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The efficacy of the serotonin antagonist ondansetron (GR 38032F) was evaluated in the prevention of nausea and vomiting induced by CMF chemotherapy in 29 breast cancer patients. At their first treatment course of CMF, all given IV on day 1 q 21 days, patients were given oral antiemetic treatment as follows: ondansetron 8 mg, 2 h prior to CMF, repeated after 5 and 10 h the day of chemotherapy and then 8 mg tds for a minimum of 3 days to a maximum of 5 days following chemotherapy. At first course of CMF, complete protection from emesis and nausea was observed in 86.2% and 62% of patients, respectively. At subsequent CMF courses with ondansetron, complete control of emesis was observed in 80% of patients. Side effects were mild and no dystonic reactions were observed. Ondansetron represents an effective, safe, and easily administered outpatient regimen. The addition of a corticosteroid to ondansetron could further improve control of CMF-induced emesis.
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  • 90
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    Breast cancer research and treatment 20 (1991), S. 125-132 
    ISSN: 1573-7217
    Keywords: amenorrhea ; breast cancer ; chemotherapy ; endocrine profile ; ovarian function
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Cyclophosphamide and other alkylating agents suppress ovarian function in pre-menopausal women. However, endocrine details remain unknown regarding the influence of patients' age and obesity on CMF-induced hormonal changes. We studied changes in endocrine profile due to chemotherapy (CMF) in 70 pre-menopausal patients with axillary node positive, stage II and/or III breast carcinoma. Plasma levels of estrone (E1), estradiol (E2), androstenedione (A2), luteinizing hormone (LH), and prolactin (PRL) were determined on day 1 and 8 of each chemocycle for 12 cycles. After receiving therapy, 23% of the women continued to have regular menstrual cycles (non-amenorrheic group). In the remaining 77%, ovarian function was suppressed, as evidenced by the onset of amenorrhea within 0–11 months (amenorrheic group). The mean time to amenorrhea was 2.83±0.33 months (SE). The time required to develop amenorrhea inversely correlated to the patient's age. Both incidence of amenorrhea and time to amenorrhea remained unaffected by either patients' obesity or the timing of chemotherapy initiation in relation to menstrual cycle phase (progestational, follicular). Plasma hormone levels fluctuated widely in both groups during the first three chemocycles. During chemocycle months 4 to 10, in the amenorrheic group, plasma E1, E2, and P declined to their baseline levels with a concomitant rise in LH levels. At this time, E1, E2, and P levels were significantly lower in amenorrheics, despite menstrual cycle associated fluctuations in the non-amenorrheic group. Estrogens (E1 and E2) gradually declined further following the onset of amenorrhea in subsequent months. Further data analysis suggests that host age or obesity did not influence CMF-induced changes in the plasma endocrine profile.
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    Breast cancer research and treatment 20 (1991), S. 155-166 
    ISSN: 1573-7217
    Keywords: breast cancer ; chemotherapy ; dose intensity ; mathematical modeling
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A mathematical model previously described is applied to the problem of selecting drug combinations for metastatic breast cancer. The model accounts for the differing single-agent activities of the drugs as well as their differing profiles of toxicity. With no bone marrow protection, combinations with cisplatin offer a small improvement in total equivalent dose over therapy with the more active single-agents. Restricting consideration to the four most commonly used agents, single-agent doxorubicin has the greatest equivalent dose. With protection for leukopenia or willingness to accept a higher incidence of severe leukopenia, a combination with large doses of cyclophosphamide, doxorubicin, and fluorouracil, and a small dose of cisplatin has greatest equivalent dose. The doublets cyclophosphamide/fluorouracil or fluorouracil/cisplatin at higher doses are almost as good. With protection for leukopenia and thrombocytopenia, a cyclophosphamide/thiotepa combination at very high doses maximizes total equivalent dose. This approach can be used to identify regimens worthy of prospective evaluation.
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  • 92
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    Breast cancer research and treatment 20 (1991), S. S11 
    ISSN: 1573-7217
    Keywords: breast cancer ; dose intensity ; autologous bone marrow transplantation ; chemotherapy ; hematopoietic growth factors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The results of systemic treatment for primary and metastatic breast cancer have plateaued in the past decade. The majority of oncologists continue to use the same chemotherapy regimens and endocrine therapies that were available in the mid 1970s. In metastatic breast cancer, still only 60–70% of patients can be expected to achieve a remission, with only 10–20% of these being a complete remission, which is usually of short duration. Metastatic breast cancer remains incurable today. Obviously, new treatment strategies are needed. The development of new active drugs, or the development of innovative ways of giving old drugs, has been disappointing in breast cancer. Similarly, combining hormones with chemotherapy, or the use of various biologic response modifiers, has not resulted in a major advance. One strategy that is currently undergoing active research is increased dose intensity of chemotherapy. This can be achieved by delivering extremely high doses of cytotoxic chemotherapy followed by hematopoietic support. A second approach involves delivering lower doses, but on a more frequent schedule than conventional programs. Preliminary results from phase II evaluation of these programs demonstrate high complete response rates, relatively short response durations, and considerable toxicity. However, 10–20% of patients treated with these regimens remain in complete remission several years after treatment, providing optimism that this approach may be effective in some patients. Advances in hematopoietic support, including autologous bone marrow transplantation (ABMT), peripheral stem cell administration, and the use of hematopoietic growth factors, have reduced toxicity. This strategy is now ready for phase III randomized trials in metastatic breast cancer as well as in the high-risk adjuvant patient to determine if high-dose therapy offers a worthwhile advantage in patients with breast cancer.
    Type of Medium: Electronic Resource
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  • 93
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    Investigational new drugs 9 (1991), S. 97-100 
    ISSN: 1573-0646
    Keywords: n-methylformamide ; melanoma ; chemotherapy ; phase II
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Sixteen patients with metastatic melanoma were treated with N-methylformamide (NMF), a polar-planar compound with in vitro cytotoxic and differentiating properties. Sixteen patients were evaluable for toxicity and 14 for response. The initial four patients received an intravenous bolus of NMF 800 mg/m2 daily for 5 consecutive days every 28 days. Because of excessive gastrointestinal toxicity, the dose was reduced to 700 mg/m2/day for the subsequent 12 patients. Two patients had immediate adverse effects from NMF; one had a grand mal seizure and the other developed severe abdominal pain. Nausea, vomiting and abdominal pain were dose-limiting. Transient elevation of liver function tests occurred in all patients. Myelosuppression was not observed. There were no objective responses among 14 evaluable patients (95% confidence limits 0–20%). One patient with pulmonary metastases had a minor response lasting 13 months. Median time to progression of disease was one month. NMF in these doses and schedule lacks clinical efficacy in the treatment of metastatic melanoma.
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  • 94
    ISSN: 1590-3478
    Keywords: Interferon ; chemotherapy ; glial tumor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Sommario In questo studio preliminare vengono presi in considerazione 28 pazienti affetti da glioblastoma multiforme. Un primo gruppo di sei pazienti è stato sottoposto esclusivamente ad immunoterapia locoregionale con β-INF. Un secondo gruppo di quattro pazienti è stato sottoposto a immunoterapia locoregionale con β-INF in associazione a chemioterapia sistemica (cis-platino+etoposide). Il Time to tumor progression dei primi due gruppi di pazienti è stato confrontato con quello di un terzo gruppo di diciotto pazienti trattati con chemioterapia sistemica.
    Notes: Abstract Dosage and schedules for the treatment of malignant glial tumors using IFN (interferon) are still uncertain and controversial. In this study we give the preliminary results of treatment in 28 patients with glioblastoma multiforme (GBM). 6 patients were treated with local injection of β-IFN through an Ommaya reservoir; 4 patients with β-IFN followed by systemic chemotherapy (Cisplatin+Etoposide), and 18 patients with chemotherapy only. Two end points were evaluated: 1) Whether or not the patients responded to treatment. 2) Length of Time to Tumor Progression(TTP) after surgery. We found that IFN alone was ineffective. Results were improved when local immunotherapy was associated with systemic chemotherapy. New drugs and investigation of possible pharmacological synergism are needed.
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  • 95
    ISSN: 1436-2813
    Keywords: estrogen receptor ; breast cancer ; nude mouse ; chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We examined the effect of chemotherapeutic agents on the estrogen receptors (ER) of breast carcinomasin vivo using human breast carcinoma strains (Br-10, T-61) serially transplanted into nude mice. When the tumor size reached approximately 1×1×1 cm, mitomycin C (MMC) at doses of 1, 2 and 4.5 mg/kg and cyclophosphamide (CPA) at a dose of 120 mg/kg, were administered once intraperitoneally, and the ERs of the tumors were measured sequentially by the dextran-coated charcoal method. Four days after the MMC administration at above doses, the binding sites of ER in Br-10 were not reduced and binding affinity was not affected. When the changes in ER content with time after the treatment with 4.5 mg/kg MMC and 120 mg/kg CPA were investigated, the ER content was found to be stable until 4 days after the treatment with both drugs, although the growth of T-61 had been significantly inhibited by the drugs. From these findings, it seems reasonable to initiate chemotherapy before endocrine therapy, since the chemotherapeutic agents did not reduce the ER content of the breast cancer strains.
    Type of Medium: Electronic Resource
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  • 96
    ISSN: 1436-2813
    Keywords: breast cancer ; hormonal status ; adjuvant therapy ; tamoxifen ; chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The ovarian and pituitary functions of 64 operable breast cancer patients undergoing adjuvant therapy with cytotoxic chemotherapy and/or tamoxifen were investigated. The post menopausal patients, divided into 3 treatment groups, one with tamoxifen alone, one with tamoxifen and chemotherapy and the other with chemotherapy alone had serum estradiol 17-β (E2) and progesterone levels lower than the evaluable limits. Although there was no significant difference in the level of estrone sulfate (E1-S) between these three groups, the level of lutainizing hormone (LH) and follicle stimulating hormone (FSH) in the patients treated with tamoxifen alone and tamoxifen and chemotherapy were significantly lower than those treated with chemotherapy alone. The decrease in gonadotropin levels induced by tamoxifen treatment was reversible as it appeared after the initiation of tamoxifen and recovered after its cessation. In the premenopausal patients, a group treated with tamoxifen and chemotherapy had significantly higher E1-S, E2 and progesterone levels and significantly lower gonadotropin levels than a group treated with chemotherapy alone or one treated with a cyclophosphamide regimen. These increases in the levels of estrogen and progesterone were also reversible, and induced by tamoxifen. Thus, adjuvant endocrinochemotherapy causes profound alteration in the hypothalamo-pituitary-ovarian axis and therefore, monitoring a variety of hormonal levels is thought to be necessary for assessing the consequences of adjuvant therapy in breast cancer patients, especially in premenopausal patients using tamoxifen.
    Type of Medium: Electronic Resource
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  • 97
    ISSN: 0942-0940
    Keywords: Adriamycin ; malignant gliomas ; glioblastoma ; chemotherapy ; tissue concentration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Eight patients with malignant gliomas verified on CT scan, received an intravenous injection of 50 mg of Adriamycin R, 24 hours prior to surgical removal of the tumour. Peroperatively, both tumour and surrounding tissue specimens were obtained for determination of the tissue concentrations of Adriamycin and its reduced metabolite Adriamycinol. It was found that Adriamycin could be detected in tumour tissue from all patients. The concentration varied between 0,9 and 4,6 nmol/g tissue. In contrast, Adriamycin could only be detected in surrounding brain tissue from one patient. In anin vitro study a human malignant glioma cell line (U-251 MG) was exposed to various concentrations of Adriamycin for 24 hours. It was found that an intracellular drug concentration above 30 nmol/g cells caused a concentration dependent inhibition of cell growth. Thus, it is likely that the poor effect of Adriamycin on patients with malignant gliomas is due to an ineffective drug accumulation in the tumour tissue.
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  • 98
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    Acta neurochirurgica 103 (1990), S. 35-46 
    ISSN: 0942-0940
    Keywords: Brain neoplasm ; chemotherapy ; malignant glioma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In recent years, there has been a great improvement in the knowledge of the biological aspects of malignant gliomas of the brain. Conversely, there has been an increase of interest in the multimodal treatment of these tumours. In this review, we have analyzed the results of the several reports which have appeared in the literature that deal with the chemotherapeutic treatment of malignant gliomas. Furthermore, some areas of biological investigation that could have an impact on pharmacological therapy are discussed.
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  • 99
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    European journal of clinical pharmacology 38 (1990), S. 525-525 
    ISSN: 1432-1041
    Keywords: clebopride ; chemotherapy ; antiemetic agents ; benzamide ; nausea and vomiting
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Type of Medium: Electronic Resource
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  • 100
    Electronic Resource
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    Springer
    European journal of clinical pharmacology 38 (1990), S. 115-120 
    ISSN: 1432-1041
    Keywords: nausea ; chemotherapy ; cancer patients ; nausea assessment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a standardized way three different methods of measuring nausea have been assessed in 849 patients enrolled in 4 double blind, randomized, clinical trials, and 2 observational studies. Nausea was measured before and 2, 4, 6, 8 and 24 hours after cancer chemotherapy by using a discrete scale (DS), a visual analogue scale (VAS) and a continuous chromatic analogue scale (ACCS), and it was evaluated according to 4 different dimensions: maximal intensity (MI) entity (E) duration (D) and quantity (Q). The distributions of nausea measurements in the population, agreement between the scales and their sensitivity, and agreement between dimensions and their sensitivity were analyzed. A uniform distribution of nausea measurements was found only in patients receiving chemotherapy without any antiemetic treatment. There was substantial equivalence of the different scales, and no advantage was shown an using an analogue (VAS) than a discrete (DS) scale. A trend toward increasing sensitivity in detecting differences as the dimensions of nausea considered became more inclusive of the various aspects of this symptom (Q more sensible than E more sensible than MI) was observed.
    Type of Medium: Electronic Resource
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