title: Adjuvant cisplatin plus methotrexate versus methotrexate, vinblastine, epirubicin, and cisplatin in locally advanced bladder cancer: results of a randomized, multicenter, phase III trial (AUO-AB 05/95).
abstract: OBJECTIVE
  Radical cystectomy as standard treatment of muscle-invasive urothelial carcinoma of the urinary bladder cures less than 50% of patients with locally advanced bladder cancer. We compared two adjuvant combination chemotherapies in patients with stage pT3a-4a and/or pathologic node-positive transitional-cell carcinoma of the bladder after radical cystectomy.
  
  
  METHODS
  A total of 327 patients were randomly assigned to either adjuvant systemic chemotherapy with three cycles of cisplatin 70 mg/qm(2) on day 1 and methotrexate 40 mg/qm(2) on days 8 and 15 of a 21-day cycle (CM) or three cycles of methotrexate 30 mg/qm(2) on days 1, 15, and 22, vinblastine 3 mg/qm(2) on days 2, 15, and 22, epirubicin 45 mg/qm(2) on day 2, and cisplatin 70 mg/qm(2) on day 2 of a 28-day cycle (M-VEC).
  
  
  RESULTS
  The hazard ratio for progression-free survival as the primary end point was 1.13 (90% CI, 0.86 to 1.48) for 163 CM patients compared with 164 M-VEC patients whose right-hand limit remained below the upper bound compatible with the noninferiority hypothesis (alpha = .0403). The 5-year progression-free, tumor-specific, and overall survival rates (point estimates +/- SE) for CM versus M-VEC were 46.3% +/- 4.6% v 48.8% +/- 4.5%, 52.0% +/- 4.6% v 52.3% +/- 4.8%, and 46.1% +/- 4.3% v 45.1% +/- 4.6%, respectively. WHO grade 3 and 4 leukopenia occurred in 7.0% of patients treated with CM and 22.2% of patients treated with M-VEC (P < .0001).
  
  
  CONCLUSIONS
  CM cannot be considered inferior to M-VEC with regard to progression-free survival of patients with locally advanced bladder cancer after radical cystectomy. Moreover, patients receiving adjuvant CM combination therapy experienced significantly less grade 3 and 4 leukopenia than patients treated with M-VEC.
authors.affiliation: Division of Biostatistics, Central Institute of Mental Health Manheim/University of Heidelberg, Germany. jan.lehmann@uniklinikum-saarland.de
authors.forename: Jan
authors.initials: J
authors.lastname: Lehmann
authors.forename: Margitta
authors.initials: M
authors.lastname: Retz
authors.forename: Christina
authors.initials: C
authors.lastname: Wiemers
authors.forename: Joachim
authors.initials: J
authors.lastname: Beck
authors.forename: Joachim
authors.initials: J
authors.lastname: Thüroff
authors.forename: Christoph
authors.initials: C
authors.lastname: Weining
authors.forename: Peter
authors.initials: P
authors.lastname: Albers
authors.forename: Detlef
authors.initials: D
authors.lastname: Frohneberg
authors.forename: Tanja
authors.initials: T
authors.lastname: Becker
authors.forename: Peter-Jörg
authors.initials: PJ
authors.lastname: Funke
authors.forename: Peter
authors.initials: P
authors.lastname: Walz
authors.forename: Sigrun
authors.initials: S
authors.lastname: Langbein
authors.forename: Frank
authors.initials: F
authors.lastname: Reiher
authors.forename: Matthias
authors.initials: M
authors.lastname: Schiller
authors.forename: Kurt
authors.initials: K
authors.lastname: Miller
authors.forename: Stephan
authors.initials: S
authors.lastname: Roth
authors.forename: Tilman
authors.initials: T
authors.lastname: Kälble
authors.forename: Donald
authors.initials: D
authors.lastname: Sternberg
authors.forename: Stefan
authors.initials: S
authors.lastname: Wellek
authors.forename: Michael
authors.initials: M
authors.lastname: Stöckle
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D018450:Disease Progression; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D016019:Survival Analysis; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000601:surgery; D014747:Vinblastine / Q000008:administration & dosage
chemical_list: D015251:Epirubicin; D014747:Vinblastine; D002945:Cisplatin; D008727:Methotrexate