title: 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.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Indiana University School of Medicine, Indianapolis 46202, USA. scott_saxman@iucc.iupui.edu
authors.forename: S B
authors.initials: SB
authors.lastname: Saxman
authors.forename: K J
authors.initials: KJ
authors.lastname: Propert
authors.forename: L H
authors.initials: LH
authors.lastname: Einhorn
authors.forename: E D
authors.initials: ED
authors.lastname: Crawford
authors.forename: I
authors.initials: I
authors.lastname: Tannock
authors.forename: D
authors.initials: D
authors.lastname: Raghavan
authors.forename: P J
authors.initials: PJ
authors.lastname: Loehrer
authors.forename: D
authors.initials: D
authors.lastname: Trump
mesh_terms: D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000556:secondary; D002945:Cisplatin / Q000627:therapeutic use*; D004317:Doxorubicin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D016016:Proportional Hazards Models; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage
chemical_list: D000903:Antibiotics, Antineoplastic; D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D014747:Vinblastine; D004317:Doxorubicin; D002945:Cisplatin; D008727:Methotrexate