title: The effect of baseline testosterone on the efficacy of degarelix and leuprolide: further insights from a 12-month, comparative, phase III study in prostate cancer patients.
abstract: OBJECTIVE
  To investigate the effects of baseline testosterone on testosterone control and prostate-specific antigen (PSA) suppression using data from a phase III trial (CS21) comparing degarelix and leuprolide in prostate cancer.
  
  
  METHODS
  In CS21, patients with histologically confirmed prostate cancer (all stages) were randomized to degarelix 240 mg for 1 month followed by monthly maintenance doses of 80 or 160 mg, or leuprolide 7.5 mg/month. Patients receiving leuprolide could receive antiandrogens for flare protection. Treatment effects on testosterone and PSA reduction, testosterone surge, and microsurges were investigated in 3 baseline testosterone subgroups: <3.5, 3.5-5.0, and >5.0 ng/mL. Data are presented for the groups receiving degarelix 240/80 mg (the approved dose) and leuprolide 7.5 mg.
  
  
  RESULTS
  Higher baseline testosterone delayed castration with both treatments. However, castrate testosterone levels and PSA suppression occurred more rapidly with degarelix irrespective of baseline testosterone. With leuprolide, the magnitude of testosterone surge and microsurges increased with increasing baseline testosterone. There was no overall correlation between baseline testosterone and initial PSA decrease in either treatment group, although PSA suppression tended to be slowest with leuprolide and fastest with degarelix in the high baseline testosterone subgroup.
  
  
  CONCLUSIONS
  Patients with high baseline testosterone may have greater risk of tumor stimulation (clinical flare) and mini-flares during gonadotrophin-releasing hormone agonist treatment and so the need for flare protection with antiandrogens in these patients is obvious, especially in metastatic disease. Although higher baseline testosterone delays castration, castrate testosterone and PSA suppression occur more rapidly with degarelix, irrespective of baseline testosterone, without the need for flare protection.
authors: Institute of Clinical Sciences, Sahlgrenska Academy at Göteborg University, Göteborg, Sweden. jan-erik.damber@urology.gu.se
authors: Jan-Erik
authors: JE
authors: Damber
authors: Teuvo L J
authors: TL
authors: Tammela
authors: Peter
authors: P
authors: Iversen
authors: Per-Anders
authors: PA
authors: Abrahamsson
authors: Laurent
authors: L
authors: Boccon-Gibod
authors: Tine Kold
authors: TK
authors: Olesen
authors: Egbert
authors: E
authors: van der Meulen
authors: Bo-Eric
authors: BE
authors: Persson
mesh_terms: D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors*; D006801:Humans; D016729:Leuprolide / Q000627:therapeutic use*; D008297:Male; D009842:Oligopeptides / Q000627:therapeutic use*; D011471:Prostatic Neoplasms / Q000097:blood* / Q000188:drug therapy*; D013739:Testosterone / Q000097:blood*
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; D013739:Testosterone; D016729:Leuprolide