A randomized comparison of cisplatin alone or in combination with methotrexate, vinblastine, and doxorubicin in patients with metastatic urothelial carcinoma: a cooperative group study.

PURPOSE A prospective randomized trial was performed to determine if the addition of methotrexate, vinblastine, and doxorubicin to cisplatin (M-VAC) imparted a response rate or a survival advantage over single-agent cisplatin in patients with advanced urothelial carcinoma. PATIENTS AND METHODS From October 1984 through May 1989, 269 patients with advanced urothelial carcinoma were entered onto this international intergroup trial and randomized to receive intravenous (IV) cisplatin (70 mg/m2) alone or with methotrexate (30 mg/m2 on days 1, 15, 22), vinblastine (3 mg/m2 on days 2, 15, 22) plus doxorubicin (30 mg/m2 on day 2). Cycles were repeated every 28 days until tumor progression or a maximum of six cycles. There were 246 fully assessable patients of whom 126 were randomized to cisplatin alone and 120 were randomized to the M-VAC regimen. RESULTS As expected, the M-VAC regimen was associated with a greater toxicity, especially leukopenia, mucositis, granulocytopenic fever, and drug-related mortality. Response rates were superior for the M-VAC regimen compared with single-agent cisplatin (39% v 12%; P less than .0001). Similarly, the progression-free survival (10.0 v 4.3 months) and overall survival (12.5 v 8.2 months) were significantly greater for the combined therapy arm. CONCLUSION Although a more toxic regimen, we found M-VAC to be superior to single-agent cisplatin with respect to response rate, duration of remission, and overall survival in patients with advanced urothelial carcinoma.