title: Antitumour activity of abiraterone acetate against metastatic castration-resistant prostate cancer progressing after docetaxel and enzalutamide (MDV3100).
abstract: BACKGROUND
  Androgen receptor (AR) signalling remains critically important in metastatic castration-resistant prostate cancer (mCRPC) as confirmed by recent phase III trials, showing a survival advantage for abiraterone acetate and enzalutamide (MDV3100). The antitumour activity of abiraterone and prednisolone in patients pre-treated with enzalutamide is as yet unknown.
  
  
  METHODS
  We investigated the antitumour activity of abiraterone and prednisolone in patients with mCRPC who had progressed following treatment with docetaxel (Taxotere) and enzalutamide. Clinical data were retrospectively analysed for prostate-specific antigen (PSA) and RECIST responses, clinical benefit and survival.
  
  
  RESULTS
  Thirty-eight patients were included in the analysis. The median age was 71 years (range 52-84); metastatic sites included bone disease in 37 patients (97%), lymph nodes in 15 patients (39%) and visceral disease in 10 patients (26%). Abiraterone was well tolerated. Three patients (8%) attained a PSA response, defined as ≥50% decline in PSA confirmed after ≥4 weeks, while seven patients (18%) had a ≥30% PSA decline. The median progression-free survival (PFS) was 2.7 months (95% CI 2.3-4.1). Of the 12 patients assessable radiologically, only 1 (8%) attained a confirmed partial response.
  
  
  CONCLUSIONS
  Abiraterone and prednisolone have modest antitumour activities in patients with mCRPC pretreated with docetaxel and enzalutamide.
authors.affiliation: Department of Cancer Medicine, Institut Gustave Roussy, University of Paris-Sud, INSERM 981, Villejuif, France. Electronic address: yohann.loriot@igr.fr.
authors.forename: Y
authors.initials: Y
authors.lastname: Loriot
authors.affiliation: Section of Medicine, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, UK.
authors.forename: D
authors.initials: D
authors.lastname: Bianchini
authors.affiliation: Department of Cancer Medicine, Institut Gustave Roussy, University of Paris-Sud, INSERM 981, Villejuif, France.
authors.forename: E
authors.initials: E
authors.lastname: Ileana
authors.affiliation: Section of Medicine, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, UK.
authors.forename: S
authors.initials: S
authors.lastname: Sandhu
authors.affiliation: Department of Cancer Medicine, Institut Gustave Roussy, University of Paris-Sud, INSERM 981, Villejuif, France.
authors.forename: A
authors.initials: A
authors.lastname: Patrikidou
authors.affiliation: Section of Medicine, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, UK.
authors.forename: C
authors.initials: C
authors.lastname: Pezaro
authors.affiliation: Department of Cancer Medicine, Institut Gustave Roussy, University of Paris-Sud, INSERM 981, Villejuif, France.
authors.forename: L
authors.initials: L
authors.lastname: Albiges
authors.affiliation: Section of Medicine, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, UK.
authors.forename: G
authors.initials: G
authors.lastname: Attard
authors.affiliation: Department of Cancer Medicine, Institut Gustave Roussy, University of Paris-Sud, INSERM 981, Villejuif, France.
authors.forename: K
authors.initials: K
authors.lastname: Fizazi
authors.affiliation: Section of Medicine, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, UK.
authors.forename: J S
authors.initials: JS
authors.lastname: De Bono
authors.affiliation: Department of Cancer Medicine, Institut Gustave Roussy, University of Paris-Sud, INSERM 981, Villejuif, France.
authors.forename: C
authors.initials: C
authors.lastname: Massard
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000736:Androstenes; D000737:Androstenols / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001549:Benzamides; D001859:Bone Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D017326:Clinical Trials, Phase III as Topic; D018572:Disease-Free Survival; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007610:Kallikreins / Q000097:blood; D008297:Male; D008875:Middle Aged; D009570:Nitriles; D010669:Phenylthiohydantoin / Q000031:analogs & derivatives* / Q000494:pharmacology; D011239:Prednisolone / Q000008:administration & dosage; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D043823:Taxoids / Q000494:pharmacology*; D016896:Treatment Outcome
chemical_list: D000736:Androstenes; D000737:Androstenols; D000970:Antineoplastic Agents; D001549:Benzamides; D009570:Nitriles; D043823:Taxoids; D000077143:Docetaxel; D010669:Phenylthiohydantoin; C540278:enzalutamide; D011239:Prednisolone; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen; C089740:abiraterone
keywords: CRPC; enzalutamide; abiraterone; hormonal manipulations