title: Clinical activity and tolerability of enzalutamide (MDV3100) in patients with metastatic, castration-resistant prostate cancer who progress after docetaxel and abiraterone treatment.
abstract: BACKGROUND
  Enzalutamide (Enz) and abiraterone acetate (AA) are hormone treatments that have a proven survival advantage in patients with metastatic, castration-resistant prostate cancer who previously received docetaxel (Doc). Recently, limited activity of AA after Enz and of Enz after AA was demonstrated in small cohort studies. Here, the authors present the activity and tolerability of Enz in patients who previously received AA and Doc in the largest cohort to date.
  
  
  METHODS
  The efficacy and tolerability of Enz were investigated in men with progressive, metastatic, castrate-resistant prostate cancer who previously received Doc and AA. Toxicity, progression-free survival, time to prostate-specific antigen (PSA) progression, and overall survival were retrospectively evaluated.
  
  
  RESULTS
  Sixty-one patients were included in the analysis. The median age was 69 years (interquartile range [IQR], 64-74 years), 57 patients (93%) had an Eastern Cooperative Oncology Group performance status from 0 to 2, 48 patients (79%) had bone metastases, 33 patients (54%) had lymph node metastases, and 13 patients (21%) had visceral metastases. The median duration of Enz treatment was 14.9 weeks (IQR, 11.1-20.0 weeks), and 13 patients (21%) had a maximum PSA decline ≥50%. The median progression-free survival was 12.0 weeks (95% confidence interval [CI], 11.1-16.0 weeks), the median time to PSA progression was 17.4 weeks (95% CI, >16.0 weeks), and the median overall survival was 31.6 weeks (95% CI, >28.7 weeks). Enz was well tolerated, and fatigue and musculoskeletal pain were the most frequent grade ≥2 adverse events. The PSA response to Doc and AA did not predict the PSA response to Enz.
  
  
  CONCLUSIONS
  Enz has modest clinical activity in patients with metastatic, castrate-resistant prostate cancer who previously received Doc and AA. PSA response to Doc and AA does not predict for PSA response to ENz.
authors.affiliation: Department of Oncology, Tergooi Hospital, Blaricum, the Netherlands.
authors.forename: Sushil
authors.initials: S
authors.lastname: Badrising
authors.forename: Vincent
authors.initials: V
authors.lastname: van der Noort
authors.forename: Inge M
authors.initials: IM
authors.lastname: van Oort
authors.forename: H Pieter
authors.initials: HP
authors.lastname: van den Berg
authors.forename: Maartje
authors.initials: M
authors.lastname: Los
authors.forename: Paul
authors.initials: P
authors.lastname: Hamberg
authors.forename: Jules L
authors.initials: JL
authors.lastname: Coenen
authors.forename: Alfons J M
authors.initials: AJ
authors.lastname: van den Eertwegh
authors.forename: Igle J
authors.initials: IJ
authors.lastname: de Jong
authors.forename: Emile D
authors.initials: ED
authors.lastname: Kerver
authors.forename: Harm
authors.initials: H
authors.lastname: van Tinteren
authors.forename: Andries M
authors.initials: AM
authors.lastname: Bergman
mesh_terms: D000368:Aged; D000736:Androstenes; D000737:Androstenols / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001549:Benzamides; D000077143:Docetaxel; D006801:Humans; D008297:Male; D008875:Middle Aged; D009570:Nitriles; D010669:Phenylthiohydantoin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000473:pathology; D016019:Survival Analysis; D043823:Taxoids / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000736:Androstenes; D000737:Androstenols; D000970:Antineoplastic Agents; D001549:Benzamides; D009570:Nitriles; D043823:Taxoids; D000077143:Docetaxel; D010669:Phenylthiohydantoin; C540278:enzalutamide; C089740:abiraterone
keywords: MDV3100; abiraterone; cross-resistance; docetaxel; enzalutamide; expanded access program; prostate cancer