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.
Written by:
Ha YS, Goodin S, DiPaola RS, Kim IY. Are you the author?
Section of Urologic Oncology and Dean and Betty Gallo Prostate Cancer Center, The Cancer Institute of New Jersey, Robert Wood Johnson Medical School, New Brunswick, New Jersey 08903, USA.
Reference: Drugs Today (Barc). 2013 Jan;49(1):7-13.
doi: 10.1358/dot.2013.49.1.1910724
PubMed Abstract
PMID: 23362491
