Enzalutamide for the treatment of castration-resistant prostate cancer.
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.
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. kimiy@umdnj.edu
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D000726:Androgen Antagonists / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001549:Benzamides; D002369:Castration / Q000379:methods; D004347:Drug Interactions; D006801:Humans; D008297:Male; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000378:metabolism; D009570:Nitriles; D010669:Phenylthiohydantoin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D011944:Receptors, Androgen / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome
C410798:AR protein, human; D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D001549:Benzamides; D009570:Nitriles; D011944:Receptors, Androgen; D010669:Phenylthiohydantoin; C540278:enzalutamide