Weekly gemcitabine in advanced bladder cancer: a preliminary report from a phase I study.

BACKGROUND: Gemcitabine (2'2-difluorodeoxycytidine; GEM) is a novel deoxycytidine analogue with promising antitumor activity, currently under phase II investigation at doses > or = 800 mg/m2/week. PATIENTS AND METHODS: The present report summarizes the results obtained in a cohort of 15 patients with metastatic bladder cancer included in a larger phase I study, receiving GEM at therapeutically active doses (> or = 875 mg/m2/week x 3 every 28 days). Except for 1 chemotherapy-naive patient, all had received prior chemotherapy with the M-VAC regimen. RESULTS: All but 1 patient were given GEM doses exceeding 1,000 mg/m2 (1 case at 875, 3 at 1,095 and 11 at 1,370 mg/m2) for a total of 50 delivered courses. One complete and 2 partial remissions were seen among 14 previously treated patients. Furthermore, 1 additional partial remission was observed in the single case with no prior chemotherapy, for an overall response rate of 27% (90% C.I. 4.3%-49.1%). All responders had visceral sites of disease. Dose-limiting hematologic toxicity was found at 1,370 mg/m2/wk as underscored by the higher number of toxic treatment delays requiring subsequent dose attenuation in 6 of 11 patients. Toxicity was mild and easily managed. It included (patients with WHO grade 2-3): leukopenia (53%), thrombocytopenia (20%), anemia (53%), AST/ALT rise (27%) and (grade 2 only) fever (60%) and emesis (40%). CONCLUSIONS: The favourable tolerability and evidence of antitumor activity of GEM in patients with bladder cancer and prior M-VAC at doses > or = 875 mg/m2/wk are encouraging and deserve confirmation in larger phase II studies.