title: Safety of enzalutamide in patients with metastatic castration-resistant prostate cancer previously treated with docetaxel: expanded access in North America.
abstract: BACKGROUND
  The open-label, single-arm enzalutamide expanded access program (EAP) in the United States and Canada evaluated the safety of enzalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC) who had previously received docetaxel.
  
  
  METHODS
  Patients (n = 507) received enzalutamide 160 mg/day until disease progression, intolerable adverse events (AEs), or commercial availability occurred. AEs and other safety variables were assessed on day 1, weeks 4 and 12, and every 12 weeks thereafter. Data following transition to commercial drug were not collected.
  
  
  RESULTS
  Median age was 71 years (range 43-97); 426 patients (83.9%) had a baseline ECOG score of ≤1. In addition to docetaxel, the majority of patients had received prior prostate cancer treatments such as abiraterone (76.1%) or cabazitaxel (28.6%). Median study treatment duration was 2.6 months (range 0.03-9.07). The most frequently reported reasons for discontinuation were commercial availability of enzalutamide (46.7%) and progressive disease (33.7%). A total of 88.2% of patients experienced AEs; 45.4% experienced AEs with a maximum grade of 1 or 2. Fatigue (39.1%), nausea (22.7%), and anorexia (14.8%) were the most commonly reported AEs. Seizure was reported in four patients (0.8%). The most commonly reported event leading to death was progression of metastatic prostate cancer (7.7%).
  
  
  CONCLUSIONS
  In this heavily pretreated EAP population with progressive mCRPC, enzalutamide was well tolerated and the safety profile was consistent with that of the AFFIRM trial.
authors: University Health Network/Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
authors: Anthony M
authors: AM
authors: Joshua
authors: Neal D
authors: ND
authors: Shore
authors: Fred
authors: F
authors: Saad
authors: Kim N
authors: KN
authors: Chi
authors: Carl A
authors: CA
authors: Olsson
authors: Urban
authors: U
authors: Emmenegger
authors: Mark
authors: M
authors: Scholz
authors: William
authors: W
authors: Berry
authors: Som D
authors: SD
authors: Mukherjee
authors: Eric
authors: E
authors: Winquist
authors: Naomi B
authors: NB
authors: Haas
authors: Margaret A
authors: MA
authors: Foley
authors: Carl
authors: C
authors: Dmuchowski
authors: Frank
authors: F
authors: Perabo
authors: Mohammad
authors: M
authors: Hirmand
authors: Nahla
authors: N
authors: Hasabou
authors: Dana
authors: D
authors: Rathkopf
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001549:Benzamides; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009570:Nitriles; D009656:North America / Q000453:epidemiology; D010669:Phenylthiohydantoin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000453:epidemiology*; D043823:Taxoids / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D009570:Nitriles; D043823:Taxoids; D000077143:Docetaxel; D010669:Phenylthiohydantoin; C540278:enzalutamide
keywords: enzalutamide; expanded access program; metastatic castration-resistant prostate cancer; safety; treatment exposure