Gemcitabine and cisplatin versus methotrexate vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: Results of a large randomized, multinational, multicenter, phase III study

Purpose: Gemcitabine plus cisplatin (OC) and methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) were compared in patients with locally advanced or metastatic transitional-cell carcinoma (TCC) of the urothelium. Patients and Methods: Patients with stage IV TCC and no prior systemic chemotherapy were randomized to OC (gemcitabine 1,000 mg/m(2) days 1, 8, and 15; cisplatin 70 mg/m(2) day 2) or standard MVAC every 28 days for a maximum of six cycles. Results: Four hundred five patients were randomized (GC, n = 203; MVAC, n = 202). The groups were well-balanced with respect to prognostic factors. Overall survival was similar on both arms (hazards ratio [HR], 1.04; 95% confidence interval [CI], 0.82 to 1.32; P =.75), as were time to progressive disease (HR, 1.05; 95% CI, 0.85 to 1.30), time to treatment failure (HR, 0.89: 95% CI, 0.72 to 1.10), and response rate (GC, 49%; MVAC, 46%). More OC patients completed six cycles of therapy, with fewer dose adjustments. The toxic death rate was 1% on the GC arm and 3% on the MVAC arm. More GC than MVAC patients had grade 3/4 anemia (27% v 18%, respectively) and thrombocytopenia (57% v 21%, respectively). On both arms, the RBC transfusion rate was 13 Of 100 cycles and grade 3/4 hemorrhage or hematuria was 2%; the platelet transfusion rate war four patients per 100 cycles and two patients per 100 cycles on GC and MVAC, respectively. More MVAC patients, compared with GC patients, had grade 3/4 neutropenia (82% v 71%, respectively), neutropenic fever (14% v 2%, respectively), neutropenic sepsis (12% v 1%, respectively), and grade 3/4 mucositis (22% v 1%, respectively) and alapecia (55% v 11%, respectively). Quality of life was maintained during treatment on both arms; however, more patients on GC fared better regarding weight, performance status, and fatigue. Conclusion: GC provides a similar survival advantage to MVAC with a better safety profile and tolerability. This better-risk benefit ratio should change the standard of care for patients with locally advanced and metastatic TCC from MVAC to OC. (C) 2000 by American Society of Clinical Oncology.