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  • 1
    ISSN: 1569-8041
    Keywords: gemcitabine ; pancreatic cancer ; phase I ; vinorelbine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose:Gemcitabine and vinorelbine are active drugs with broadspectrum of activity and manageable toxicity in clinical trials. The aims ofthis study were to describe the toxicity, to determine the dose-limitingtoxicity, and to define the doses of gemcitabine and vinorelbine to berecommended for phase II studies in patients with advanced cancers. Patients and methods:Drugs were given as 30–min infusions on day1 and 8 (vinorelbine before gemcitabine) every 3 weeks. Thirty-six patients(male : female ratio 25 : 11; mean age 54, PS 〉60) were treated including1 retroperitoneal sarcoma, 7 head and neck, 10 lung, 4 thyroid, 6 pancreatic,1 bladder, 2 ovary, 2 gastric, 1 rectum, 1 unknown primary, and 1 renal cellcarcinoma. Doses of gemcitabine/vinorelbine ranged from 800/20mg/m2 to 1500/30 mg/m2. Results:The dose-limiting toxicity was neutropenia. A transientgrade 2–3 elevation of transaminases was frequently observed at severaldose-levels, although this toxicity did not appear to be dose dependant andwas reversible at day 21 before the next cycle. Other toxicities were mild andeasily manageable, consisting of fatigue and flu-like syndromes. Since the MTDwas not reach at the higher dose-level, the recommended dose level of thegemcitabine–vinorelbine combination was 1500/30 mg/m2. Onetoxic death due to hematologic toxicity was reported in a heavily pretreatedpatient who underwent prior chemotherapy and pelvic radiotherapy. A total of12 patients were treated at the recommended dose level which was associatedwith grade 3–4 neutropenia in 3 of 12 patients and in 22.9% ofcycles. Conclusions:This study estimates that the recommended dose forphase II studies of gemcitabine–vinorelbine is 1500/30 mg/m2at day 1 and 8 every three weeks. A careful monitoring of the hematologictoxicity is recommended in heavily pretreated patients and in patients whoreceived pelvic radiotherapy. Partial responses observed in a patient with anadvanced cisplatin–5–fluorouracil-resistant pancreatic adenocarcinomaand in a patient with mesothelioma support further evaluation of thiscombination in patients with tumors refractory to classical antitumor agents.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1569-8041
    Keywords: chemotherapy ; mitomycin ; recurrent ; undifferentiated carcinoma of nasopharyngeal type
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: This phase-II study was conducted to investigate the potential benefit from the addition of mitomycin to a conventional anthracycline-cisplatin- and 5-fluorouracil-based chemotherapy for recurrent and metastatic undifferentiated carcinoma of nasopharyngeal type (UCNT). Patients and methods: Between July 1989 and December 1991, 44 consecutive patients (M/F 36/8; median age: 45, range 20–72; performance status (PS) 0: 20 patients, PS 1: 14 patients, PS 2: 10 patients) with recurrent or metastatic UCNT were entered in this study after complete clinical, biological, and radiological pre-therapeutic work-ups. Chemotherapy (FMEP regimen) consisted of 800 mg/m2/day 5-fluorouracil in continuous infusion from day 1 to day 4 combined with 70 mg/m2 epirubicin, 10 mg/m2 mitomycin, and 100 mg/m2 cisplatin on day 1, every four weeks for six cycles. Mitomycin was delivered in cycles 1, 3, and 5 only. Eleven patients had isolated loco-regional recurrences, 12 patients had local recurrences associated with distant metastasis, and 21 patients had metastasis only. Toxicity and response were evaluated according to WHO criteria. Toxicity: Grade 3–4 neutropenia was observed in 122 of 212 evaluable cycles (57%) and 39 of 44 patients (89%); febrile neutropenia occurred in 16 patients (36%) and 24 cycles (11.3%). Grade 3–4 thrombocytopenia was observed in 27 patients (61%) and 45 cycles (21%), including 27 of 45 cycles (60%) with mitomycin. Grade 3 anemia was noted in 18 patients (40%) and 23 cycles (11%), including 18 of 23 cycles (78%) with mitomycin. Grade 3–4 mucositis occurred in 25 cycles (11%) and 14 patients (32%), mainly in those previously treated with radiation therapy in the head and neck area. There were four treatment-related deaths (9%); three of them neutropenia-related, and one of cardiac toxicity. Response: Forty-four patients were evaluable for response: There were 23 of 44 objective responses (52%), including six complete responses (13%), and 17 partial responses (38%). Additional radiotherapy was given to 13 patients after documentation of response: Nasopharyngeal tumor + cervical nodes (eight patients) and/or on bone metastasis sites (five patients); mediastinal lymph nodes (one patient). At a median follow-up of 87 months (range 71–100), five patients are alive and in continuous complete remission. The median survival time was 14 months and the median time to progression nine months. Conclusion: The regimen under study is active in recurrent/metastatic UCNT, but associated with excessive toxicity.
    Type of Medium: Electronic Resource
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