Enzalutamide

Enzalutamide (INN, USAN)

Clinical data
Pronunciation	ex-TAN-dee
Trade names	Xtandi
AHFS/Drugs.com	xtandi
License data	US FDA: Enzalutamide
Pregnancy category	US: X (Contraindicated)
Routes of administration	Oral (capsules)
ATC code	L02BB04 (WHO)
Legal status
Legal status	US: ℞-only
Pharmacokinetic data
Bioavailability	89.7% (rat)
Protein binding	97–98%
Metabolism	Hepatic (primarily CYP2C8 and CYP3A4)
Biological half-life	8–9 days
Excretion	Renal (71%), biliary (14%)
Identifiers
IUPAC name 4-(3-(4-Cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluoro-N-methylbenzamide
Synonyms	MDV3100
CAS Number	915087-33-1
PubChem (CID)	15951529
IUPHAR/BPS	6812
ChemSpider	13093347
UNII	93T0T9GKNU
KEGG	D10218
ChEBI	CHEBI:68534 Y
ECHA InfoCard	100.231.722
Chemical and physical data
Formula	C21H16F4N4O2S
Molar mass	464.44 g·mol−1
3D model (Jmol)	Interactive image
SMILES N#Cc1c(C(F)(F)F)cc(N2C(C(C)(C)N(c3ccc(C(N(C)[H])=O)c(F)c3)C2=S)=O)cc1
InChI InChI=1S/C21H16F4N4O2S/c1-20(2)18(31)28(12-5-4-11(10-26)15(8-12)21(23,24)25)19(32)29(20)13-6-7-14(16(22)9-13)17(30)27-3/h4-9H,1-3H3,(H,27,30) Key:WXCXUHSOUPDCQV-UHFFFAOYSA-N

Enzalutamide (brand name Xtandi) is a synthetic non-steroidal antiandrogen (NSAA) which was developed by the pharmaceutical company Medivation for the treatment of metastatic, castration-resistant prostate cancer. Medivation has reported up to an 89% decrease in serum prostate specific antigen (PSA) levels after a month of taking the drug. Research suggests that enzalutamide may also be effective in the treatment of certain types of breast cancer. In August 2012, the United States (U.S.) Food and Drug Administration (FDA) approved enzalutamide for the treatment of castration-resistant prostate cancer.

Enzalutamide is clinically active in metastatic castration-resistant prostate cancer. PSA level decreased more than 50% in 40 of 65 chemo-naive patients and 38 of 75 chemotherapy-treated patients. Median time to radiographic progression was 56 weeks for chemo-naive patients and 25 weeks for the post-chemotherapy population.

Medivation conducted an international phase III trial that began in September 2009 known as AFFIRM. The aim of this trial was determine the safety and effectiveness of enzalutamide in patients who have previously failed chemotherapy treatment with docetaxel. In November 2011, this trial was stopped early after an interim analysis revealed that patients given the drug lived for approximately 5 months longer than those taking placebo. FDA approval was granted in August 2012.

Another phase III trial known as PREVAIL is investigating the effectiveness of enzalutamide with patients who have not yet received chemotherapy. On October 22, 2013, Medivation and Astellas announced that the PREVAIL trial met both co-primary endpoints of overall survival, with a 30% reduction in the risk of death compared with placebo (hazard ratio = 0.7; 95% confidence interval, range of 0.59–0.83), and radiographic progression-free survival, with an 81% reduction in risk of radiographic progression or death compared with placebo (hazard ratio = 0.19); 95% conficence interval, 0.15-0.23). In addition, a phase II trial began in March 2011 comparing enzalutamide with bicalutamide in prostate cancer patients who have progressed while on gonadotropin-releasing hormone (GnRH) analogue therapy (e,g., leuprorelin) or surgical castration.