Springer Online Journal Archives 1860-2000
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.
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