title: Enzalutamide in castration-resistant prostate cancer patients progressing after docetaxel and abiraterone.
abstract: BACKGROUND
  Abiraterone, an androgen synthesis inhibitor, has been successfully used in the treatment of castration-resistant prostate cancer (CRPC) for 2 yr. Enzalutamide is a second-generation nonsteroidal antiandrogen that has recently been approved for the same indication.
  
  
  OBJECTIVE
  This is the first study to evaluate the effectiveness of enzalutamide after failure of abiraterone.
  
  
  METHODS
  Thirty-five patients were identified as having received sequential therapy with abiraterone followed by enzalutamide. All patients had undergone prior docetaxel chemotherapy, and no patient had received ketoconazole.
  
  
  METHODS
  Posttreatment changes in prostate-specific antigen (PSA) were used to determine the activity of enzalutamide in patients who had received prior abiraterone.
  
  
  CONCLUSIONS
  The median duration of abiraterone treatment was 9.0 mo (range: 2.0-19.0 mo). Of the 35 patients, 16 (45.7%) achieved a >50% decline in PSA, and 14 (40%) had a rising PSA as the best response. The median duration of subsequent enzalutamide treatment was 4.9 mo (Kaplan-Meier estimate; 95% confidence interval [CI], 2.4-7.4). Seven of 16 CRPC patients who were initially abiraterone-sensitive (43.8%) and 3 of 19 CRPC patients who were initially abiraterone-insensitive (15.8%) showed a >50% PSA decline while taking enzalutamide. Of the 35 patients, 17 (48.6%) were primarily enzalutamide-resistant and showed a rising PSA as the best response. Median time to progression was 4.0 mo (95% CI, 2.0-6.0) for 18 of 35 patients with at least one declining PSA value while taking enzalutamide (51.4%). Of the 17 patients who were assessable radiologically, only 1 (2.9%) attained a confirmed partial response. Small sample size was the major limitation.
  
  
  CONCLUSIONS
  Enzalutamide treatment achieved only a modest response rate in patients progressing after abiraterone. Although cross-resistance between abiraterone and enzalutamide was a common phenomenon, it was not inevitable, and a small but significant number of patients showed significant benefit from sequential treatment.
authors.affiliation: Department of Urology, Ulm University Medical Center, Ulm, Germany. Electronic address: ajschrader@gmx.de.
authors.forename: Andres Jan
authors.initials: AJ
authors.lastname: Schrader
authors.forename: Martin
authors.initials: M
authors.lastname: Boegemann
authors.forename: Carsten-H
authors.initials: CH
authors.lastname: Ohlmann
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Schnoeller
authors.forename: Laura-Maria
authors.initials: LM
authors.lastname: Krabbe
authors.forename: Turkan
authors.initials: T
authors.lastname: Hajili
authors.forename: Florian
authors.initials: F
authors.lastname: Jentzmik
authors.forename: Michael
authors.initials: M
authors.lastname: Stoeckle
authors.forename: Mark
authors.initials: M
authors.lastname: Schrader
authors.forename: Edwin
authors.initials: E
authors.lastname: Herrmann
authors.forename: Marcus V
authors.initials: MV
authors.lastname: Cronauer
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000736:Androstenes; D000737:Androstenols / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D018450:Disease Progression; D000077143:Docetaxel; D006801:Humans; D008297:Male; D008875:Middle Aged; D009570:Nitriles; D010669:Phenylthiohydantoin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010865:Pilot Projects; D017430:Prostate-Specific Antigen / Q000097:blood; D064129:Prostatic Neoplasms, Castration-Resistant / Q000097:blood / Q000188:drug therapy*; D043823:Taxoids / Q000627:therapeutic use*; D017211:Treatment Failure
chemical_list: D000736:Androstenes; D000737:Androstenols; D000970:Antineoplastic Agents; D001549:Benzamides; D009570:Nitriles; D043823:Taxoids; D000077143:Docetaxel; D010669:Phenylthiohydantoin; C540278:enzalutamide; D017430:Prostate-Specific Antigen; C089740:abiraterone
keywords: Abiraterone; Biochemical failure; Cross-resistance; Enzalutamide; MDV3100; Sequential therapy