title: Neoadjuvant cisplatinum based combination chemotherapy in patients with invasive bladder cancer: a combined analysis of two Nordic studies.
abstract: OBJECTIVE
  A Nordic collaborative group assessed the effectiveness of cisplatinum based combination chemotherapy prior to cystectomy in two consecutive trials. We analyzed overall survival in all patients and in prespecified subgroups defined by preoperative T-stage, gender and age.
  
  
  METHODS
  The studies included in 1985-1997 620 patients with clinically T1G3, T2-T4aNXM0 urothelial bladder cancer and WHO performance </=2. Platinum was combined with adriamycin in the first and with methotrexate in the second trial. In the first of the studies, preoperative radiotherapy was used in both arms. Individual patient data were used. No patients were lost to follow-up. The median follow-up was 4.7 years. A fixed effect model was used to combine the results of the two trials. Subgroup analyses were performed for T-stages, gender and age groups. All analyses were done according to intention to treat.
  
  
  RESULTS
  The combined study results showed a hazard ratio of 0.80 (95% confidence interval 0.64-0.99) for overall survival in favor of neoadjuvant treatment. Survival was 56% at five years in the experimental group versus 48% in the control group, thus corresponding to an eight percent absolute risk reduction after neoadjuvant chemotherapy. We could not substantiate any differences in effect by subgroup.
  
  
  CONCLUSIONS
  In a combined analysis of two trials within the same study organization and the same clinical and biological domain, neoadjuvant platinum based combination chemotherapy was associated with a 20% reduction in the relative hazard in probability of death.
authors.affiliation: Department of Urology, Akademiska University Hospital, SE-751 85 Uppsala, Sweden. amir.sherif@swipnet.se
authors.forename: Amir
authors.initials: A
authors.lastname: Sherif
authors.forename: Lars
authors.initials: L
authors.lastname: Holmberg
authors.forename: Erkki
authors.initials: E
authors.lastname: Rintala
authors.forename: Oddvar
authors.initials: O
authors.lastname: Mestad
authors.forename: Jonas
authors.initials: J
authors.lastname: Nilsson
authors.forename: Sten
authors.initials: S
authors.lastname: Nilsson
authors.forename: Per-Uno
authors.initials: PU
authors.lastname: Malmström
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D016009:Chi-Square Distribution; D002945:Cisplatin / Q000008:administration & dosage; D015653:Cystectomy; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D016032:Randomized Controlled Trials as Topic; D012537:Scandinavian and Nordic Countries; D016019:Survival Analysis; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy / Q000601:surgery
chemical_list: D004317:Doxorubicin; D002945:Cisplatin; D008727:Methotrexate