title: Safety and effectiveness of enzalutamide in men with metastatic, castration-resistant prostate cancer.
abstract: BACKGROUND
  Enzalutamide (MDV3100) is a second-generation androgen receptor antagonist that improves survival in metastatic, castration-resistant prostate cancer (mCRPC). Alternatives include chemotherapy, radiation, immunotherapy and abiraterone.
  
  
  METHODS
  The Phase I/II study showed early evidence of efficacy and determined that fatigue is the dose-limiting toxicity. Two randomized, placebo-controlled trials have demonstrated superiority of enzalutamide 160 mg by mouth daily over placebo in terms of overall survival, radiographic progression-free survival as well as a broad range of secondary and exploratory end points in men who had received previous chemotherapy (AFFIRM) and in those who were chemotherapy naive (PREVAIL). Common side effects include fatigue, arthralgias and constipation. A post hoc analysis from AFFIRM found that enzalutamide is safe and effective in men aged ≥ 75 years. The Phase I/II studies as well as AFFIRM and PREVAIL are described in this review.
  
  
  CONCLUSIONS
  Enzalutamide extends overall and progression-free survival and is associated with robust response rates and quality of life benefits in men with mCRPC. Enzalutamide has not been proven to be effective in biochemically relapsed disease or in castration-sensitive prostate cancer. It should not be used in men at high risk for seizure, and patients should be counseled about the increased risk of falls.
authors: Portland Veterans Affairs Medical Center, OHSU Knight Cancer Institute , 3710 SW US Veterans Hospital Road, Portland, 97239 OR , USA +1 503 220 8262 ; +1 503 494 6197 ; graffj@ohsu.edu.
authors: Julie N
authors: JN
authors: Graff
authors: Max J
authors: MJ
authors: Gordon
authors: Tomasz M
authors: TM
authors: Beer
mesh_terms: D059002:Androgen Receptor Antagonists / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D006801:Humans; D008297:Male; D009362:Neoplasm Metastasis; D009570:Nitriles; D010669:Phenylthiohydantoin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000473:pathology; D011788:Quality of Life; D016032:Randomized Controlled Trials as Topic
chemical_list: D059002:Androgen Receptor Antagonists; D000970:Antineoplastic Agents; D001549:Benzamides; D009570:Nitriles; D010669:Phenylthiohydantoin; C540278:enzalutamide
keywords: MDV3100; androgen receptor; castration-resistant prostate cancer; enzalutamide