Treatment of metastatic castration-resistant prostate cancer (mCRPC) with enzalutamide

Crit Rev Oncol Hematol. 2016 Oct:106:14-24. doi: 10.1016/j.critrevonc.2016.07.005. Epub 2016 Jul 15.

Abstract

Prostate cancer is initially responsive to androgen deprivation therapy, but most patients eventually develop castration-resistant disease. Enzalutamide is an androgen receptor (AR) inhibitor that targets several steps in the AR signaling pathway and has shown significant efficacy in the treatment of metastatic castration-resistant prostate cancer in patients with or without prior chemotherapy. To provide optimal treatment, it is important to understand the implications of enzalutamide use in the context of other therapies, as recent findings have suggested cross-resistance occurs between and within drug classes. Mutations and splice variants of AR also impact the course of prostate cancer. Future strategies involving enzalutamide should account for previous exposure to taxanes or antiandrogen therapies and the presence of AR variants that could affect efficacy.

Keywords: Antiandrogen therapy; Combination therapy; Cross resistance; Enzalutamide; Primary resistance.

Publication types

  • Review

MeSH terms

  • Androgen Receptor Antagonists / adverse effects
  • Androgen Receptor Antagonists / therapeutic use
  • Benzamides
  • Clinical Trials, Phase I as Topic
  • Clinical Trials, Phase II as Topic
  • Clinical Trials, Phase III as Topic
  • Drug Resistance, Neoplasm
  • Humans
  • Male
  • Nitriles
  • Phenylthiohydantoin / adverse effects
  • Phenylthiohydantoin / analogs & derivatives*
  • Phenylthiohydantoin / therapeutic use
  • Prostatic Neoplasms, Castration-Resistant / drug therapy*
  • Prostatic Neoplasms, Castration-Resistant / pathology
  • Randomized Controlled Trials as Topic

Substances

  • Androgen Receptor Antagonists
  • Benzamides
  • Nitriles
  • Phenylthiohydantoin
  • enzalutamide