title: Androgen dynamics and serum PSA in patients treated with abiraterone acetate.
abstract: BACKGROUND
  We analyzed the potential of abiraterone acetate (henceforth abiraterone) to reduce androgen levels below lower limits of quantification (LLOQ) and explored the association with changes in PSA decline in metastatic castration-resistant prostate cancer (mCRPC) patients.
  
  
  METHODS
  COU-AA-301 is a 2:1 randomized, double-blind, placebo-controlled study comparing abiraterone (1000 mg q.d.) plus low-dose prednisone (5 mg b.i.d.) with placebo plus prednisone in mCRPC patients post docetaxel. Serum testosterone, androstenedione and dehydroepiandrosterone sulfate from baseline to week 12 were measured by novel ultrasensitive two-dimensional liquid chromatography coupled to tandem mass spectrometry assays in a subset of subjects in each arm (abiraterone plus prednisone, n=80; prednisone, n=38). The association between PSA response (< or =50% baseline) and undetectable androgens (week 12 androgen level below LLOQ) was analyzed using logistic regression.
  
  
  RESULTS
  A significantly greater reduction in serum androgens was observed with abiraterone plus prednisone versus prednisone (all P < or = 0.0003), reaching undetectable levels for testosterone (47.2% versus 0%, respectively). A positive association was observed between achieving undetectable serum androgens and PSA decline (testosterone: odds ratio=1.54; 95% confidence interval: 0.546-4.347). Reduction of androgens to undetectable levels did not occur in all patients achieving a PSA response, and a PSA response did not occur in all patients achieving undetectable androgen levels.
  
  
  CONCLUSIONS
  Abiraterone plus prednisone significantly reduced serum androgens, as measured by ultrasensitive assays and was generally associated with PSA response. However, androgen decline did not uniformly predict PSA decline suggesting ligand-independent or other mechanisms for mCRPC progression.
authors.affiliation: University of California San Francisco, San Francisco, CA, USA.
authors.forename: C J
authors.initials: CJ
authors.lastname: Ryan
authors.affiliation: Janssen Research & Development, Los Angeles, CA, USA.
authors.forename: W
authors.initials: W
authors.lastname: Peng
authors.affiliation: Janssen Research & Development, Los Angeles, CA, USA.
authors.forename: T
authors.initials: T
authors.lastname: Kheoh
authors.affiliation: Janssen Research & Development, Los Angeles, CA, USA.
authors.forename: E
authors.initials: E
authors.lastname: Welkowsky
authors.affiliation: Janssen Research & Development, Los Angeles, CA, USA.
authors.forename: C M
authors.initials: CM
authors.lastname: Haqq
authors.affiliation: Endocrine Sciences, LabCorp, Calabasas, CA, USA.
authors.forename: D W
authors.initials: DW
authors.lastname: Chandler
authors.affiliation: Memorial Sloan Kettering Cancer Center and Weill-Cornell Medical College, New York, NY, USA.
authors.forename: H I
authors.initials: HI
authors.lastname: Scher
authors.affiliation: Janssen Research & Development, Menlo Park, CA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Molina
mesh_terms: D000069501:Abiraterone Acetate; D000728:Androgens / Q000097:blood*; D000736:Androstenes / Q000627:therapeutic use*; D004311:Double-Blind Method; D006801:Humans; D007610:Kallikreins / Q000097:blood*; D008297:Male; D011241:Prednisone / Q000627:therapeutic use; D017430:Prostate-Specific Antigen / Q000097:blood*; D064129:Prostatic Neoplasms, Castration-Resistant / Q000097:blood* / Q000188:drug therapy*; D013739:Testosterone / Q000097:blood; D016896:Treatment Outcome
chemical_list: D000728:Androgens; D000736:Androstenes; D013739:Testosterone; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen; D000069501:Abiraterone Acetate; C089740:abiraterone; D011241:Prednisone