title: Phase III trial of methotrexate, vinblastine, doxorubicin, and cisplatin versus carboplatin and paclitaxel in patients with advanced carcinoma of the urothelium.
abstract: BACKGROUND
  The regimens of carboplatin plus paclitaxel (CP) and methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) were compared in patients with advanced urothelial carcinoma.
  
  
  METHODS
  Patients with metastatic urothelial carcinoma were randomized to receive either CP (paclitaxel at a dose of 225 mg/m(2) and carboplatin [targeted area under the concentration-time curve (AUC) of 6] given every 21 days) or the standard M-VAC dosage.
  
  
  RESULTS
  Eighty-five patients were randomized to the respective treatment regimens (41 to CP and 44 to M-VAC). Response rates and overall survival were similar for both treatment arms. Patients treated with CP had an overall response rate of 28.2% (95% binomial confidence interval, 15.0-44.9%) compared with an overall response rate of 35.9% for the M-VAC arm (95% binomial confidence interval, 21.2-52.8%) (P = 0.63, Fisher exact test). The median progression-free survival among patients who were treated with M-VAC was 8.7 months and was 5.2 months for patients receiving CP (P = 0.24, log-rank test). At a median follow-up of 32.5 months, the median survival for patients treated with M-VAC was 15.4 months versus 13.8 months for patients treated with CP (P = 0.65, log-rank test). Patients treated with M-VAC were found to have more severe worst-degree toxicities compared with patients treated with CP (P = 0.0001). There were no significant differences with regard to quality of life as assessed by the Functional Assessment of Cancer Therapy-Bladder (FACT-BL) instrument (P = 0.33).
  
  
  CONCLUSIONS
  Interpretation of the results of this study must be made with caution because the study failed to reach its accrual goal. Patients treated with CP had a median survival of 13.8 months compared with 15.4 months for patients treated with M-VAC. Patients treated with CP appeared in general to better tolerate their treatment; however, there were no significant differences noted with regard to measured quality of life parameters.
authors.affiliation: Department of Hematology/Oncology and Urologic Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA. dreicer@cc.ccf.org
authors.forename: Robert
authors.initials: R
authors.lastname: Dreicer
authors.forename: Judith
authors.initials: J
authors.lastname: Manola
authors.forename: Bruce J
authors.initials: BJ
authors.lastname: Roth
authors.forename: William A
authors.initials: WA
authors.lastname: See
authors.forename: Steven
authors.initials: S
authors.lastname: Kuross
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Edelman
authors.forename: Gary R
authors.initials: GR
authors.lastname: Hudes
authors.forename: George
authors.initials: G
authors.lastname: Wilding
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage; D016019:Survival Analysis; D016896:Treatment Outcome; D014571:Urologic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014747:Vinblastine / Q000008:administration & dosage
chemical_list: D014747:Vinblastine; D004317:Doxorubicin; D016190:Carboplatin; D017239:Paclitaxel; D002945:Cisplatin; D008727:Methotrexate