title: Adjuvant chemotherapy with cisplatin and gemcitabine versus chemotherapy at relapse in patients with muscle-invasive bladder cancer submitted to radical cystectomy: an Italian, multicenter, randomized phase III trial.
abstract: BACKGROUND
  The purpose of the study was to evaluate the benefit of adjuvant chemotherapy (AC) versus surgery alone in patients with muscle-invasive bladder cancer (MIBC).
  
  
  METHODS
  One hundred and ninety-four patients with pT2G3, pT3-4, N0-2 transitional cell bladder carcinoma were randomly allocated to control (92 patients) or to four courses of AC (102 patients). These latter patients were further randomly assigned to receive gemcitabine 1000 mg/m(2) days 1, 8 and 15 and cisplatin 70 mg/m(2) day 2 or gemcitabine as above plus cisplatin 70 mg/m(2) day 15, every 28 days.
  
  
  RESULTS
  At a median follow-up of 35 months, the 5-year overall survival (OS) was 48.5%, with no difference between the two arms [P = 0.24, hazard ratio (HR) 1.29, 95% confidence interval (CI) 0.84-1.99]. Mortality hazard was significantly correlated with Nodes (N) and Tumor (T) stage. The control and AC arms had comparable disease-free survival (42.3% and 37.2%, respectively; P = 0.70, HR 1.08, 95% CI 0.73-1.59). Only 62% of patients received the planned cycles. A significant higher incidence of thrombocytopenia was observed in patients receiving cisplatin on day 2 (P = 0.006). A similar global quality of life was observed in the two arms.
  
  
  CONCLUSIONS
  The study was underpowered to demonstrate that AC with cisplatin and gemcitabine improves OS and disease-free survival in patients with MIBC.
authors.affiliation: Department of Medical Oncology, Regina Elena Cancer Institute, Rome. Electronic address: cognetti@ifo.it.
authors.forename: F
authors.initials: F
authors.lastname: Cognetti
authors.affiliation: Division of Medical Oncology, Belcolle Hospital, Viterbo.
authors.forename: E M
authors.initials: EM
authors.lastname: Ruggeri
authors.affiliation: Department of Medical Oncology, Regina Elena Cancer Institute, Rome.
authors.forename: A
authors.initials: A
authors.lastname: Felici
authors.affiliation: Department of Urology, Regina Elena Cancer Institute, Rome.
authors.forename: M
authors.initials: M
authors.lastname: Gallucci
authors.affiliation: Department of Urology, San Giovanni Bosco Hospital, Torino.
authors.forename: G
authors.initials: G
authors.lastname: Muto
authors.affiliation: Division of Medical Oncology, Belcolle Hospital, Viterbo.
authors.forename: C F
authors.initials: CF
authors.lastname: Pollera
authors.affiliation: Department of Medical Oncology, Policlinico Universitario, Cagliari.
authors.forename: B
authors.initials: B
authors.lastname: Massidda
authors.affiliation: Departments of Medical Oncology and of Oncology, Biology and Genetics (Biostatistics Unit), National Cancer Research Institute and University, Genova; Departments of Medical Oncology and of Oncology, Biology and Genetics, National Cancer Research Institute and University, Genova.
authors.forename: A
authors.initials: A
authors.lastname: Rubagotti
authors.affiliation: Department of Biostatistics, Regina Elena Cancer Institute, Rome, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Giannarelli
authors.affiliation: Departments of Medical Oncology and of Oncology, Biology and Genetics, National Cancer Research Institute and University, Genova.
authors.forename: F
authors.initials: F
authors.lastname: Boccardo
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D015653:Cystectomy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007558:Italy; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D016016:Proportional Hazards Models; D012008:Recurrence; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D002945:Cisplatin; D000093542:Gemcitabine