title: Translating clinical trials to clinical practice: outcomes of men with metastatic castration resistant prostate cancer treated with docetaxel and prednisone in and out of clinical trials.
abstract: BACKGROUND
  Multiple factors can influence outcomes of patients receiving identical interventions in clinical trials and in routine practice. Here, we compare outcomes of men with metastatic castrate-resistant prostate cancer (mCRPC) treated with docetaxel and prednisone in routine practice and in clinical trials.
  
  
  METHODS
  We reviewed patients with mCRPC treated with docetaxel at Princess Margaret Cancer Centre. Primary outcomes were overall survival and PSA response rate. Secondary outcomes were reasons for discontinuation and febrile neutropenia. Outcomes were compared for men treated in routine practice and in clinical trials, and with data from the TAX 327 study.
  
  
  RESULTS
  From 2001 to 2011, 438 men were treated, of whom 357 received 3-weekly docetaxel as first-line chemotherapy: 314 in routine practice and 43 in clinical trials. Trial patients were younger and had better performance status. Median survival was 13.6 months [95% confidence interval (95% CI) 12.1-15.1 months] in routine practice and 20.4 months (95% CI 17.4-23.4 months, P = 0.007) within clinical trials, compared with 19.3 months (95% CI 17.6-21.3 months, P < 0.001) in the TAX 327 study. PSA response rates were 45%, 54%, and 53%, respectively (P = NS). Reasons for treatment discontinuation were similar although trial patients received more cycles (median: 6 versus 8 versus 9.5, P < 0.001). Rates of febrile neutropenia were 9.6, 0, and 3% (P < 0.001) while rates of death within 30 days of last dose were 4%, 0%, and 3%, respectively (P = NS).
  
  
  CONCLUSIONS
  Survival of patients with mCRPC treated with docetaxel in routine practice is shorter than for men included in trials and is associated with more toxicity.
authors.affiliation: Division of Medical Oncology and Hematology, University of Toronto, Toronto.
authors.forename: A J
authors.initials: AJ
authors.lastname: Templeton
authors.forename: F E
authors.initials: FE
authors.lastname: Vera-Badillo
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.forename: M
authors.initials: M
authors.lastname: Attalla
authors.forename: P
authors.initials: P
authors.lastname: De Gouveia
authors.forename: R
authors.initials: R
authors.lastname: Leibowitz-Amit
authors.forename: J J
authors.initials: JJ
authors.lastname: Knox
authors.forename: M
authors.initials: M
authors.lastname: Moore
authors.forename: S S
authors.initials: SS
authors.lastname: Sridhar
authors.forename: A M
authors.initials: AM
authors.lastname: Joshua
authors.forename: G R
authors.initials: GR
authors.lastname: Pond
authors.forename: E
authors.initials: E
authors.lastname: Amir
authors.forename: I F
authors.initials: IF
authors.lastname: Tannock
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D000077143:Docetaxel; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage; D017430:Prostate-Specific Antigen / Q000097:blood; D064129:Prostatic Neoplasms, Castration-Resistant / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D043823:Taxoids; D000077143:Docetaxel; D017430:Prostate-Specific Antigen; D011241:Prednisone
keywords: clinical trial; docetaxel; prostate cancer; routine practice