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

Scott B. Saxman, Kathleen J. Propert, Lawrence H. Einhorn, E. David Crawford, Ian Tannock, Derek Raghavan, Patrick J. Loehrer, Donald Trump

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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/m2 on day 1) or combination chemotherapy with methotrexate (30 mg/m2 on days 1, 15, and 22), vinblastine (3 mg/m2 on days 2, 15, and 22), doxorubicin (30 mg/m2 on day 2), and cisplatin (70 mg/m2 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.

Original languageEnglish (US)
Pages (from-to)2564-2569
Number of pages6
JournalJournal of Clinical Oncology
Issue number7
StatePublished - Jul 1997


ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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