Phase III trial of fluorouracil, interferon alfa-2b, and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in metastatic or unresectable urothelial cancer

Purpose: Previously, we developed a novel biochemotherapy regimen combining interferon alfa-2b with fluorouracil and cisplatin (FAP). We now report the results of a prospective randomized trial comparing FAP with methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC), the standard chemotherapy regimen for locally advanced and metastatic urothelial cancer. The purpose of this study was to compare the response rates and overall survival of patients with metastatic or unresectable urothelial cancer treated with these two chemotherapy regimens. Patients and Methods: Between October 1992 and September 1999, 172 previously untreated patients were registered and randomly assigned to treatment with either FAP or M-VAC. Patients were followed until their death. Results: The pretreatment clinical characteristics of the groups were similar except for sex (P < .01). Sex did not affect prognosis or survival. The objective response rate for patients assigned to FAP was 42% (35 of 83 patients), with complete response observed in eight (10%) of 83 patients. Among the patients assigned to M-VAC, 51 (59%) of 86 had an objective response, with complete response observed in 21 (24%) of 86. The Kaplan-Meier estimate of median survival was 12.5 months for both groups. Both regimens were quite toxic, with more mucocutaneous toxicity in the FAP arm and more myelosuppression in the M-VAC arm. Conclusion: Although overall survival was not significantly different, patients assigned to M-VAC had a much better chance of responding to front-line therapy. Thus, FAP is very likely to be inferior to M-VAC and is certainly no less toxic. FAP cannot be recommended as part of the standard armamentarium for urothelial cancer.