title: Enzalutamide: a novel antiandrogen for patients with castrate-resistant prostate cancer.
abstract: Enzalutamide (MDV3100, Xtandi, Medivation\Astellas) is an oral inhibitor of androgen receptor signaling that blocks androgen receptor interaction, inhibits translocation of the androgen receptor to the nucleus, impairs androgen receptor binding to DNA, and inhibits coactivator recruitment and receptor-mediated DNA transcription. In a phase III randomized study comparing enzalutamide with placebo in men with progressive castration-resistant prostate cancer (CRPC) who were previously treated with docetaxel, enzalutamide showed an improvement in overall survival (18.4 vs. 13.6 months, HR, 0.63; P < 0.001). In addition, all secondary endpoints including proportion of patients with prostate-specific antigen (PSA) decline, soft-tissue response, quality-of-life response, time to PSA progression, radiographic progression-free survival, and the time to the first radiographic skeletal event all significantly favored patients treated with enzalutamide. Fatigue, diarrhea, and hot flashes were common in patients treated with enzalutamide, with seizures reported in 5 (0.6%) of the patients. Enzalutamide is a novel therapy that very potently blocks the androgen signaling pathway, which is unregulated during the development of CRPC. The preclinical studies along with the pivotal trials that led to its approval by the U.S. Food and Drug Administration (FDA) in September 2012 will be reviewed.
authors.affiliation: Department of Medical Oncology, Thomas Jefferson University and Hospital, Philadelphia, Pennsylvania 19107, USA.
authors.forename: Jean
authors.initials: J
authors.lastname: Hoffman-Censits
authors.forename: Wm Kevin
authors.initials: WK
authors.lastname: Kelly
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000008:administration & dosage*; D059002:Androgen Receptor Antagonists; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage*; D001549:Benzamides; D002369:Castration; D018572:Disease-Free Survival; D017277:Drug Approval; D019008:Drug Resistance, Neoplasm; D064420:Drug-Related Side Effects and Adverse Reactions / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009570:Nitriles; D010669:Phenylthiohydantoin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D000726:Androgen Antagonists; D059002:Androgen Receptor Antagonists; D018931:Antineoplastic Agents, Hormonal; D001549:Benzamides; D009570:Nitriles; D010669:Phenylthiohydantoin; C540278:enzalutamide; D017430:Prostate-Specific Antigen