Gemcitabine in locally advanced and/or metastatic bladder cancer.

Gemcitabine is a promising new drug in patients with locally advanced and/or metastatic transitional cell carcinoma of the urothelium. The drug has been tested as a single-agent in one phase I study and four phase II studies. Gemcitabine was administered on days 1, 8 and 15 every 28 days with a dose in the phase II studies ranging from 1000 to 1250 mg/m(2). Response rates for single-agent gemcitabine in as well previously untreated as cisplatin-based pretreated patients ranged from 23 to 29% with CR rates between 4 and 13%. Toxicities were mild to modest and generally without grade 4 toxicities. The combination of gemcitabine and cisplatin has been tested in three phase II studies. Gemcitabine was administered in a dose of 1000 mg/m(2) on days 1, 8 and 15 every 28 days whereas the cisplatin dose and schedule varied. In one study, cisplatin was given in a dose of 35 mg/m(2) on days 1, 8, and 15 together with gemcitabine; in the two other studies in a dose of 70-75 mg/m(2) on day 1 or 2 in each treatment course. The response rates ranged from 42 to 66% with CR rates of 18, 21 and 28%. Median survival was reported in two of the studies, 12.5 and 13.2 months, respectively. Toxicities were generally manageable although the weekly schedule of cisplatin resulted in a high degree of grade 3-4 neutropenia and thrombocytopenia. Thus, the schedule has been optimized by use of monthly cisplatin in a dose of 70 to 75 mg/m(2). The two-drug combination of gemcitabine and cisplatin has also been compared with MVAC in a randomized phase III trial. Gemcitabine was administered in a dose of 1000 mg/m(2) on days 1, 8 and 15 and cisplatin in a dose of 70 mg/m(2) on day 2 every 28 days. The study was initiated late in 1996 and the planned recruitment of 400 patients was reached at the end of October 1998. The results are now eagerly awaited. Preliminary results for gemcitabine tested in two- and three-drug combinations with new agents such as paclitaxel have indicated response rates of up to 79% and these combinations should be further explored.

RCT Entities:   Population Interventions Outcomes