title: Phase III trial of fluorouracil, interferon alpha-2b, and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in metastatic or unresectable urothelial cancer.
abstract: OBJECTIVE
  Previously, we developed a novel biochemotherapy regimen combining interferon alpha-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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Center for Genitourinary Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Arlene O
authors.initials: AO
authors.lastname: Siefker-Radtke
authors.forename: Randall E
authors.initials: RE
authors.lastname: Millikan
authors.forename: Shi-Ming
authors.initials: SM
authors.lastname: Tu
authors.forename: Dennis F
authors.initials: DF
authors.lastname: Moore
authors.forename: Terry L
authors.initials: TL
authors.lastname: Smith
authors.forename: Dallas
authors.initials: D
authors.lastname: Williams
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Logothetis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004317:Doxorubicin / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage; D008297:Male; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D011446:Prospective Studies; D011994:Recombinant Proteins; D015996:Survival Rate; D016896:Treatment Outcome; D014571:Urologic Neoplasms / Q000188:drug therapy* / Q000401:mortality; D014747:Vinblastine / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D014747:Vinblastine; D004317:Doxorubicin; D002945:Cisplatin; D005472:Fluorouracil; D008727:Methotrexate