title: Enzalutamide: a review of its use in metastatic, castration-resistant prostate cancer.
abstract: Enzalutamide (MDV3100, XTANDI(®)) is an androgen receptor inhibitor that is indicated for the treatment of metastatic, castration-resistant, prostate cancer (mCRPC) that has progressed despite treatment with docetaxel. This article reviews the pharmacology, efficacy and tolerability of enzalutamide relevant to this indication. In a randomized, double-blind, placebo-controlled, multinational, phase III trial in patients with mCRPC progressing after docetaxel therapy, enzalutamide significantly prolonged overall survival (OS), delayed prostate specific antigen progression and prolonged radiographic progression-free survival and time to the first skeletal event. The median OS was 18.4 months in the enzalutamide group and 13.6 months in the placebo group, which represents a 37 % reduction in the mortality risk in the enzalutamide group. Enzalutamide was also associated with significant benefits in health-related quality of life and in pain palliation. Enzalutamide was generally as well tolerated as placebo during the trial, with most adverse events at a mild or moderate level of severity. Enzalutamide carries a small increased risk of seizures that appears to be dose-dependent. Enzalutamide is an efficacious and well tolerated treatment for this severe, rapidly progressive disease.
authors.affiliation: Adis, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, North Shore, 0754, Auckland, New Zealand, demail@springer.com.
authors.forename: Mark
authors.initials: M
authors.lastname: Sanford
mesh_terms: D059002:Androgen Receptor Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001549:Benzamides; D006801:Humans; D008297:Male; D009362:Neoplasm Metastasis; D009570:Nitriles; D010669:Phenylthiohydantoin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000473:pathology; D016032:Randomized Controlled Trials as Topic; D011944:Receptors, Androgen / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: C410798:AR protein, human; D059002:Androgen Receptor Antagonists; D000970:Antineoplastic Agents; D001549:Benzamides; D009570:Nitriles; D011944:Receptors, Androgen; D010669:Phenylthiohydantoin; C540278:enzalutamide