WEEKLY GEMCITABINE IN ADVANCED BLADDER-CANCER - A PRELIMINARY-REPORT FROM A PHASE-I STUDY

Background: Gemcitabine (2'2-difluorodeoxycytidine; GEM) is a novel de oxycytidine analogue with promising antitumor activity, currently unde r phase II investigation at doses greater-than-or-equal-to 800 mg/m2/w eek. Patients and methods: The present report summarizes the results o btained in a cohort of 15 patients with metastatic bladder cancer incl uded in a larger phase I study, receiving GEM at therapeutically activ e doses (greater-than-or-equal-to 875 mg/m2/week x 3 every 28 days). E xcept for 1 chemotherapy-naive patient, all had received prior chemoth erapy with the M-VAC regimen. Results: All but 1 patient were given GE M doses exceeding 1,000 mg/m2 (1 case at 875, 3 at 1,095 and 11 at 1,3 70 mg/m2) for a total of 50 delivered courses. One complete and 2 part ial remissions were seen among 14 previously treated patients. Further more, 1 additional partial remission was observed in the single case w ith 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-lim iting hematologic toxicity was found at 1,370 mg/m2/wk as underscored by the higher number of toxic treatment delays requiring subsequent do se attenuation in 6 of 11 patients. Toxicity was mild and easily manag ed. It included (patients with WHO grade 2-3): leukopenia (53%), throm bocytopenia (20%), anemia (53%), AST/ALT rise (27%) and (grade 2 only) fever (60%) and emesis (40%). Conclusions: The favourable tolerabilit y and evidence of antitumor activity of GEM in patients with bladder c ancer and prior M-VAC at doses greater-than-or-equal-to 875 mg/m2/wk a re encouraging and deserve confirmation in larger phase II studies.