title: Long-term tolerability and efficacy of degarelix: 5-year results from a phase III extension trial with a 1-arm crossover from leuprolide to degarelix.
abstract: OBJECTIVE
  To demonstrate the safety and efficacy of up to 5 years of degarelix treatment and the effects of crossing over from leuprolide to degarelix in the extension phase of a phase III pivotal 1-year trial.
  
  
  METHODS
  Patients receiving degarelix who completed the 1-year trial continued on 80 mg (n = 125) or 160 mg (n = 126) maintenance doses. Patients who received leuprolide were rerandomized to degarelix 240/80 mg (n = 69) or 240/160 mg (n = 65). Safety and tolerability were assessed (primary end point), as well as testosterone and prostate-specific antigen levels and prostate-specific antigen progression-free survival (secondary end points).
  
  
  RESULTS
  Adverse event frequency was similar between both the groups. Adverse events included initial injection site reactions, hot flushes, and increased weight. Testosterone and prostate-specific antigen values during the extension study were similar to those seen during the 1-year trial in patients who continued on degarelix or crossed over from leuprolide. The prostate-specific antigen progression-free survival hazard rate was decreased significantly after the crossover in the leuprolide to degarelix group (from 0.20 to 0.09; P = .002), whereas in patients who continued on degarelix, the rate did not change significantly. In patients with baseline prostate-specific antigen >20 ng/mL, the same hazard rate change pattern was observed on crossover (from 0.38 to 0.19; P = .019).
  
  
  CONCLUSIONS
  Degarelix was well tolerated; no safety concerns were identified. The significant prostate-specific antigen progression-free survival benefit established for degarelix over leuprolide during year 1 remained consistent at 5 years.
authors.affiliation: Department of Urologic Oncology, School of Medicine, University of Colorado Denver, Aurora, CO. Electronic address: david.crawford@uchsc.edu.
authors.forename: E David
authors.initials: ED
authors.lastname: Crawford
authors.affiliation: Carolina Urologic Research Center, Myrtle Beach, SC.
authors.forename: Neal D
authors.initials: ND
authors.lastname: Shore
authors.affiliation: Division of Surgery and Urology, Duke University Medical Center, Durham, NC.
authors.forename: Judd W
authors.initials: JW
authors.lastname: Moul
authors.affiliation: Department of Urology, University Clinics Saint Luc/Catholic University of Leuven, Brussels, Belgium.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Tombal
authors.affiliation: Department of Urology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Fritz H
authors.initials: FH
authors.lastname: Schröder
authors.affiliation: Department of Urology, Charité University Medicine Berlin, Berlin, Germany.
authors.forename: Kurt
authors.initials: K
authors.lastname: Miller
authors.affiliation: Department of Urology, CHU Hospital Bichat-Claude Bernard, Paris, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Boccon-Gibod
authors.affiliation: Ferring Pharmaceuticals, Copenhagen, Denmark.
authors.forename: Anders
authors.initials: A
authors.lastname: Malmberg
authors.affiliation: Ferring Pharmaceuticals, Copenhagen, Denmark.
authors.forename: Tine Kold
authors.initials: TK
authors.lastname: Olesen
authors.affiliation: Ferring Pharmaceuticals, Saint-Prex, Switzerland.
authors.forename: Bo-Eric
authors.initials: BE
authors.lastname: Persson
authors.affiliation: Division of Urology, University of Toronto, Ontario, Canada.
authors.forename: Laurence
authors.initials: L
authors.lastname: Klotz
mesh_terms: D018592:Cross-Over Studies; D018572:Disease-Free Survival; D006801:Humans; D016729:Leuprolide / Q000627:therapeutic use*; D008297:Male; D009842:Oligopeptides / Q000009:adverse effects / Q000627:therapeutic use*; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy*; D013739:Testosterone / Q000097:blood; D013997:Time Factors
chemical_list: D009842:Oligopeptides; C431566:acetyl-2-naphthylalanyl-3-chlorophenylalanyl-1-oxohexadecyl-seryl-4-aminophenylalanyl(hydroorotyl)-4-aminophenylalanyl(carbamoyl)-leucyl-ILys-prolyl-alaninamide; D013739:Testosterone; D017430:Prostate-Specific Antigen; D016729:Leuprolide