Long-term follow-up of a phase III intergroup study of cisplatin alone or in combination with methotrexate, vinblastine, and doxorubicin in patients with metastatic urothelial carcinoma: A cooperative group study

Purpose: A previously reported randomized intergroup trial demonstrated that combination chemotherapy with methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) was superior to single-agent cisplatin in patients with advanced urothelial carcinoma, We conducted a long-term analysis of patients included in the intergroup trial to examine factors associated with long-term survival, Patients and Methods: Two-hundred fifty-five assessable patients with urothelial carcinoma were randomized to receive either single-agent cisplatin (70 mg/m(2) on day 1) or combination chemotherapy with methotrexate (30 mg/m(2) on days 1, 15, and 22), vinblastine (3 mg/m(2) on days 2, 15, and 22), doxorubicin (30 mg/m(2) on day 2), and cisplatin (70 mg/m(2) on day 2), Courses were repeated every 28 days, The association between patient characteristics and survival was assessed using Cox proportional hazards models. Results: With long-term follow-up evaluation, survival in the M-VAC arm continues to be superior to cisplatin (P = .00015, log-rank test), Predictors of survival include performance status, histology, and the presence of liver or bone metastasis. Only 3.7% of the patients randomized to M-VAC are alive and continuously disease-free at 6 years, Conclusion: Long-term follow-up evaluation of the intergroup trial confirms that M-VAC is superior to single-agent cisplatin in patients with advanced urothelial carcinoma; however, durable progression-free survival is rare. Patients with non-transitional-cell histology, poor performance status, and/or bone or visceral involvement fare poorly and are unlikely to benefit significantly from M-VAC chemotherapy. (C) 1997 by American Society of Clinical Oncology.