title: Enzalutamide: an evidence-based review of its use in the treatment of prostate cancer.
abstract: BACKGROUND
  Enzalutamide is an oral androgen receptor (AR) signaling inhibitor that was specifically engineered to overcome castration-resistant prostate cancer (CRPC) harboring AR amplification or overexpression. Enzalutamide has demonstrated significant activity in men with metastatic CRPC.
  
  
  OBJECTIVE
  To update the evidence and provide an overview of the available data on enzalutamide.
  
  
  METHODS
  Peer reviewed articles published and listed in Medline Search were reviewed. In addition, relevant ASCO and ESMO abstracts were searched. The activity of enzalutamide is mediated by potently antagonizing the full-length AR, impairing translocation of the AR from the cytoplasm into the nucleus, and inhibiting the transcriptional activity of the AR by modulating the interaction of the AR with androgen-response elements in gene promoter regions. Enzalutamide has a favorable safety profile and the most common adverse events include fatigue, hot flashes and headache; 1% of patients experienced seizure.
  
  
  CONCLUSIONS
  The AFFIRM phase III study evaluated the clinical utility of treatment with enzalutamide in men with docetaxel-refractory metastatic CRPC. Enzalutamide improved overall survival compared to placebo, with a median overall survival of 18.4 months versus 13.6 months respectively.
  
  
  CONCLUSIONS
  Enzalutamide has demonstrated impressive efficacy in men with metastatic CRPC, moving swiftly from a phase I/II study to two pivotal phase III trials testing this agent in both chemotherapy-pretreated as well as chemotherapy-naïve CRPC patients. Ongoing studies are aiming to explore the utility of enzalutamide in earlier stages of the disease, and to investigate the optimal sequencing and combination of enzalutamide with other standard and novel therapies for prostate cancer.
authors.affiliation: Division of Hematology/Oncology, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Ali R
authors.initials: AR
authors.lastname: Golshayan
authors.forename: Emmanuel S
authors.initials: ES
authors.lastname: Antonarakis
keywords: MDV3100; androgen receptor; antiandrogen; castration-resistant prostate cancer; enzalutamide