title: Dutasteride treatment over 2 years delays prostate-specific antigen progression in patients with biochemical failure after radical therapy for prostate cancer: results from the randomised, placebo-controlled Avodart After Radical Therapy for Prostate Cancer Study (ARTS).
abstract: BACKGROUND
  Rising prostate-specific antigen (PSA) levels after radical therapy are indicative of recurrent or residual prostate cancer (PCa). This biochemical recurrence typically predates clinically detectable metastatic disease by several years. Management of patients with biochemical recurrence is controversial.
  
  
  OBJECTIVE
  To assess the effect of dutasteride on progression of PCa in patients with biochemical failure after radical therapy.
  
  
  METHODS
  Randomised, double-blind, placebo-controlled trial in 294 men from 64 centres across 9 European countries.
  
  
  METHODS
  The 5α-reductase inhibitor, dutasteride.
  
  
  METHODS
  The primary end point was time to PSA doubling from start of randomised treatment, analysed by log-rank test stratified by previous therapy and investigative-site cluster. Secondary end points included time to disease progression and the proportion of subjects with disease progression.
  
  
  CONCLUSIONS
  Of the 294 subjects randomised (147 in each treatment group), 187 (64%) completed 24 mo of treatment and 107 discontinued treatment prematurely (71 [48%] of the placebo group, 36 [24%] of the dutasteride group). Dutasteride significantly delayed the time to PSA doubling compared with placebo after 24 mo of treatment (p<0.001); the relative risk (RR) reduction was 66.1% (95% confidence interval [CI], 50.35-76.90) for the overall study period. Dutasteride also significantly delayed disease progression (which included PSA- and non-PSA-related outcomes) compared with placebo (p<0.001); the overall RR reduction in favour of dutasteride was 59% (95% CI, 32.53-75.09). The incidence of adverse events (AEs), serious AEs, and AEs leading to study withdrawal were similar between the treatment groups. A limitation was that investigators were not blinded to PSA levels during the study.
  
  
  CONCLUSIONS
  Dutasteride delayed the biochemical progression of PCa in patients with biochemical failure after radical therapy for clinically localised disease. The safety and tolerability of dutasteride were generally consistent with previous experience.
  
  
  BACKGROUND
  ClinicalTrials.gov, NCT00558363.
authors.affiliation: Erasmus Medical Centre, Rotterdam, The Netherlands. secr.schroder@erasmusmc.nl
authors.forename: Fritz
authors.initials: F
authors.lastname: Schröder
authors.forename: Chris
authors.initials: C
authors.lastname: Bangma
authors.forename: Javier C
authors.initials: JC
authors.lastname: Angulo
authors.forename: Antonio
authors.initials: A
authors.lastname: Alcaraz
authors.forename: Marc
authors.initials: M
authors.lastname: Colombel
authors.forename: Tom
authors.initials: T
authors.lastname: McNicholas
authors.forename: Teuvo L
authors.initials: TL
authors.lastname: Tammela
authors.forename: Indrani
authors.initials: I
authors.lastname: Nandy
authors.forename: Ramiro
authors.initials: R
authors.lastname: Castro
mesh_terms: D058891:5-alpha Reductase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage* / Q000009:adverse effects; D001378:Azasteroids / Q000008:administration & dosage*; D018450:Disease Progression; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D000068538:Dutasteride; D005060:Europe; D006801:Humans; D007610:Kallikreins / Q000097:blood*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000097:blood*; D011468:Prostatectomy / Q000009:adverse effects; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D015854:Up-Regulation
chemical_list: D058891:5-alpha Reductase Inhibitors; D018931:Antineoplastic Agents, Hormonal; D001378:Azasteroids; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen; D000068538:Dutasteride