title: Additional analysis of the secondary end point of biochemical recurrence rate in a phase 3 trial (CS21) comparing degarelix 80 mg versus leuprolide in prostate cancer patients segmented by baseline characteristics.
abstract: BACKGROUND
  Recent data suggest prostate-specific antigen (PSA) progression may predict overall survival in prostate cancer patients.
  
  
  OBJECTIVE
  To compare the activity of degarelix and leuprolide regarding PSA recurrence-free survival.
  
  
  METHODS
  Phase 3, 1-yr, multicentre, randomised, open-label trial comparing the efficacy and safety of degarelix at 240 mg for 1 mo, and then 80 mg monthly (240/80 mg); degarelix at 240 mg for 1 mo, and then 160 mg monthly; and leuprolide at 7.5 mg/mo. Overall, 610 patients with histologically confirmed prostate cancer (all stages), for whom androgen deprivation therapy was indicated, were included. The primary end point of this trial has been reported previously; the protocolled and exploratory subgroup analyses reported in this paper focus on degarelix at 240/80 mg (dose approved by the US Food and Drug Administration and the European Medicine Evaluation Association for the treatment of patients with hormone-naive advanced prostate cancer).
  
  
  METHODS
  PSA progression-free survival (two consecutive increases in PSA of 50% compared with nadir and ≥ 5 ng/ml on two consecutive measurements at least 2 wk apart or death) and change in PSA were reviewed. Effects of baseline disease stage (localised, locally advanced, and metastatic) and PSA level (<10, 10-20, >20-50, and >50 ng/ml) were analysed.
  
  
  CONCLUSIONS
  Patients receiving degarelix showed a significantly lower risk of PSA progression or death compared with leuprolide (p=0.05). PSA recurrences occurred mainly in patients with advanced disease and exclusively in those with baseline PSA >20 ng/ml. Patients with PSA >20 ng/ml had a significantly longer time to PSA recurrence with degarelix (p=0.04). The relatively low number of patients in each subgroup is a limitation of this study.
  
  
  CONCLUSIONS
  These results generate the hypothesis that degarelix at 240/80 mg offers improved PSA control compared with leuprolide. PSA recurrences occurred almost exclusively in patients with metastatic prostate cancer or high baseline PSA during this 1-yr study. Further studies are warranted to confirm these findings.
authors: Cliniques Universitaires Saint Luc/Université Catholique de Louvain, Brussels, Belgium. bertrand.tombal@uclouvain.be
authors: Bertrand
authors: B
authors: Tombal
authors: Kurt
authors: K
authors: Miller
authors: Laurent
authors: L
authors: Boccon-Gibod
authors: Fritz
authors: F
authors: Schröder
authors: Neal
authors: N
authors: Shore
authors: E David
authors: ED
authors: Crawford
authors: Judd
authors: J
authors: Moul
authors: Jens-Kristian
authors: JK
authors: Jensen
authors: Tine
authors: T
authors: Kold Olesen
authors: Bo-Eric
authors: BE
authors: Persson
mesh_terms: D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage*; D018572:Disease-Free Survival; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors*; D006801:Humans; D016729:Leuprolide / Q000008:administration & dosage*; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000453:epidemiology; D009842:Oligopeptides / Q000008:administration & dosage*; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology
chemical_list: D018931:Antineoplastic Agents, Hormonal; D009842:Oligopeptides; C431566:acetyl-2-naphthylalanyl-3-chlorophenylalanyl-1-oxohexadecyl-seryl-4-aminophenylalanyl(hydroorotyl)-4-aminophenylalanyl(carbamoyl)-leucyl-ILys-prolyl-alaninamide; D007987:Gonadotropin-Releasing Hormone; D017430:Prostate-Specific Antigen; D016729:Leuprolide