1992/07/01 by Patrick J. Loehrer, Lawrence H. Einhorn, Paul Elson +7 · 1 citation
Medicine · #Bladder and Urothelial Cancer Treatments #Chemotherapy #Cisplatin #Gastroenterology #Internal medicine #Leukopenia #Medicine #Methotrexate #Mucositis #Oncology #Randomized controlled trial #Regimen #Surgery #Urinary Tract Infections Management #Urinary and Genital Oncology Studies #Urology #Vinblastine
paper · doi:10.1200/jco.1992.10.7.1066
openalex publication_date 1992/07/01 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01
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.