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.
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.
Authors: Joaquim Bellmunt; Hans von der Maase; Graham M Mead; Iwona Skoneczna; Maria De Santis; Gedske Daugaard; Andreas Boehle; Christine Chevreau; Luis Paz-Ares; Leslie R Laufman; Eric Winquist; Derek Raghavan; Sandrine Marreaud; Sandra Collette; Richard Sylvester; Ronald de Wit Journal: J Clin Oncol Date: 2012-02-27 Impact factor: 44.544
Authors: Lisa A Hammond-Thelin; Melanie B Thomas; Michiko Iwasaki; James L Abbruzzese; Yvonne Lassere; Christina A Meyers; Paulo Hoff; Johann de Bono; Jody Norris; Hitoshi Matsushita; Akira Mita; Eric K Rowinsky Journal: Invest New Drugs Date: 2010-09-14 Impact factor: 3.850
Authors: J Lehmann; M Retz; G Steiner; P Albers; E Jaeger; A Knuth; C Lippert; M Koser; K Stockamp; C Otto; H Melchior; C Fassmann; C Potratz; T Loch; H G Derigs; T Becker; T Kälble; H-J Piechota; L Hertle; S Weinknecht; L Weissbach; M Al-Mwalad; A Hamza; H Henss; D Brkovic; S Pomer; J Roloff; P Walz; R Muschter; U Tunn; E Winter; P Bub; U Kaldenbach; S Roth; A Brauers; G Jakse; A E Richter; M Wirth; J Hartlapp; H Van Ahlen; M Stöckle Journal: Urologe A Date: 2003-04-02 Impact factor: 0.639
Authors: Maria De Santis; Joaquim Bellmunt; Graham Mead; J Martijn Kerst; Michael Leahy; Pablo Maroto; Iwona Skoneczna; Sandrine Marreaud; Ronald de Wit; Richard Sylvester Journal: J Clin Oncol Date: 2009-09-28 Impact factor: 44.544