Enzalutamide for the treatment of castration-resistant prostate cancer

Drugs Today (Barc). 2013 Jan;49(1):7-13. doi: 10.1358/dot.2013.49.1.1910724.


Castration-resistant prostate cancer (CRPC) remains a major clinical challenge, given the mechanistic heterogeneity due to a complex signal transduction network. Enzalutamide (MDV-3100), recently approved by the U.S. Food and Drug Administration (FDA) at a dose of 160 mg/day for the treatment of CRPC, blocks androgen signaling by directly binding to the androgen receptor (AR) and inhibiting nuclear translocation and coactivator recruitment of the ligand-receptor complex. In preclinical studies, enzalutamide has been shown to block the binding of AR to DNA, resulting in apoptosis and retardation of tumor growth. Clinically, a phase I/II study (N = 140) revealed that enzalutamide had an optimal safety profile and significant antitumor activity in patients with CRPC regardless of prior chemotherapy. In the AFFIRM phase III trial (N = 1,199), oral enzalutamide significantly improved survival in men with metastatic CRPC after chemotherapy. Currently, a phase III trial (PREVAIL) is under way to determine the effectiveness of enzalutamide in patients who have not received prior docetaxel chemotherapy.

Publication types

  • Review

MeSH terms

  • Androgen Antagonists / adverse effects
  • Androgen Antagonists / pharmacokinetics
  • Androgen Antagonists / therapeutic use*
  • Animals
  • Antineoplastic Agents, Hormonal / adverse effects
  • Antineoplastic Agents, Hormonal / pharmacokinetics
  • Antineoplastic Agents, Hormonal / therapeutic use*
  • Castration* / methods
  • Drug Interactions
  • Humans
  • Male
  • Neoplasms, Hormone-Dependent / drug therapy*
  • Neoplasms, Hormone-Dependent / metabolism
  • Phenylthiohydantoin / adverse effects
  • Phenylthiohydantoin / analogs & derivatives*
  • Phenylthiohydantoin / pharmacokinetics
  • Phenylthiohydantoin / therapeutic use
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / mortality
  • Prostatic Neoplasms / pathology
  • Receptors, Androgen / drug effects
  • Receptors, Androgen / metabolism
  • Signal Transduction / drug effects
  • Treatment Outcome


  • AR protein, human
  • Androgen Antagonists
  • Antineoplastic Agents, Hormonal
  • Receptors, Androgen
  • Phenylthiohydantoin
  • enzalutamide