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Enzalutamide (INN, USAN) (brand name Xtandi and former developmental code name MDV3100) is a synthetic, non-steroidal pure antiandrogen which was developed by the pharmaceutical company Medivation for the treatment of metastatic castration-resistant prostate cancer.^[2] Medivation has reported up to an 89% decrease in serum prostate specific antigen (PSA) levels after a month of taking the drug.^[3] Early pre-clinical studies also suggest that enzalutamide inhibits breast cancer cell growth.^[4]^[5] In August 2012, the United States (U.S.) Food and Drug Administration (FDA) approved enzalutamide for the treatment of castration-resistant prostate cancer.^[6]^[7]

Discovery

Enzalutamide was discovered by Charles Sawyers who is now at Memorial Sloan–Kettering Cancer Center and Michael Jung at UCLA.^[8]^[9]

Preclinical pharmacology

Enzalutamide has approximately five-fold higher binding affinity for the androgen receptor (AR) compared to bicalutamide.^[10] As opposed to bicalutamide, enzalutamide does not promote translocation of AR to the cell nucleus and in addition prevents binding of AR to deoxyribonucleic acid (DNA) and AR to coactivator proteins.^[10] As such, it has been described as an AR signaling inhibitor in addition to antagonist.^[11]

When LNCaP cells (a prostate cancer cell line) engineered to express elevated levels of AR (as found in patients with advanced prostate cancer) were treated with enzalutamide, the expression of androgen-dependent genes PSA and TMPRSS2 was down regulated in contrast to bicalutamide where the expression was upregulated.^[10] In VCaP cells which over-express the AR, enzalutamide induced apoptosis whereas bicalutamide did not.^[10] Furthermore, enzalutamide behaves as an antagonist of the W741C mutant AR in contrast to bicalutamide which behaves as a pure agonist when bound to the W741C mutant.^[10]

Clinical studies

Enzalutamide is clinically-active in metastatic castration-resistant prostate cancer.^[12] PSA level decreased more than 50% in 40/65 chemo-naive patients and 38/75 chemotherapy-treated patients.^[12] Median time to radiographic progression was 56 weeks for chemo-naive patients and 25 weeks for the post-chemotherapy population.^[13]

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.^[14] 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.^[15] FDA approval was granted in August 2012.^[6]^[16]

Another phase III trial known as PREVAIL is investigating the effectiveness of enzalutamide with patients who have not yet received chemotherapy.^[17] On October 22, 2011, 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).^[18] 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.^[19]^[20]

Adverse effects

Notable side effects of enzalutamide seen in clinical trials have included gynecomastia, breast pain/tenderness, fatigue, diarrhea, hot flashes, headache, sexual dysfunction, and, less commonly, seizures.^[11]^[21]^[22]^[23]

In regards to seizures, they have occurred in approximately 1% of patients treated with enzalutamide in clinical trials.^[11]^[22] This is thought to be due to enzalutamide crossing the blood-brain-barrier^[24]^[25] and exerting off-target binding to and inhibition of the GABA_A receptor in the central nervous system (it has been found to inhibit the GABA_A receptor in vitro^[25]^[26] and induces seizures in animals at high doses).^[11]^[22] In addition to seizures, other potentially GABA_A receptor-related side effects observed with enzalutamide treatment in clinical trials have included anxiety, insomnia, vertigo, paresthesia, and headache.^[1] Due to its ability to lower the seizure threshold, patients with known seizure disorders or brain injury should be closely monitored during enzalutamide treatment.^[27]

There is a single case report of posterior reversible encephalopathy syndrome (PRES) with enzalutamide treatment.^[28]

Pharmacokinetics

Enzalutamide has a very long half-life of 8–9 days.^[1]

Enzalutamide is reported to be a strong inducer of the enzyme CYP3A4 and a moderate inducer of CYP2C9 and CYP2C19.^[29]

References

^ ^a ^b ^c ^d Jerome Z. Litt (25 January 2013). Litt's Drug Eruptions and Reactions Manual, 19th Edition. CRC Press. pp. 148–. ISBN 978-1-84214-599-9.
^ "Medivation's MDV3100 Shown to Be Effective in a Preclinical Model of Hormone-Refractory Prostate Cancer". Press release. Medivation, Inc. 2007-02-26. Retrieved 2009-05-10.
^ "Medivation's MDV3100 Demonstrates Substantial PSA Reductions In First Patient Groups Treated In Phase 1-2 Hormone Refractory Prostate Cancer Trial". Medical News Today. 2007-11-06. Retrieved 2009-05-10.
^ "Preclinical Evaluation of Enzalutamide in Breast Cancer Models".
^ "Medivation and Astellas Announce New Preclinical Study Results Showing MDV3100 Blocks Breast Cancer Cell Growth". Press Release. MarketWatch. 2011-08-04. Retrieved 2011-09-25.
^ ^a ^b "FDA approves new treatment for a type of late stage prostate cancer". press release. United States Food and Drug Administration. 2012-08-31.
^ Anna Azvolinsky (September 4, 2012). "FDA Approves Enzalutamide (Xtandi) for Late-Stage Prostate Cancer". CancerNetwork.
^ Borman S (2008). "New prostate cancer agent class". Chemical & Engineering News 86 (38): 84–87. doi:10.1021/cen-v086n038.p084.
^ Jung ME, Ouk S, Yoo D, Sawyers CL, Chen C, Tran C, Wongvipat J (April 2010). "Structure-activity relationship for thiohydantoin androgen receptor antagonists for castration-resistant prostate cancer (CRPC)". J. Med. Chem. 53 (7): 2779–96. doi:10.1021/jm901488g. PMC 3180999. PMID 20218717.
^ ^a ^b ^c ^d ^e Tran C, Ouk S, Clegg NJ, Chen Y, Watson PA, Arora V, Wongvipat J, Smith-Jones PM, Yoo D, Kwon A, Wasielewska T, Welsbie D, Chen CD, Higano CS, Beer TM, Hung DT, Scher HI, Jung ME, Sawyers CL (May 2009). "Development of a second-generation antiandrogen for treatment of advanced prostate cancer". Science 324 (5928): 787–90. doi:10.1126/science.1168175. PMC 2981508. PMID 19359544.
^ ^a ^b ^c ^d Antonarakis ES (2013). "Enzalutamide: The emperor of all anti-androgens". Transl Androl Urol 2 (2): 119–120. PMC 3785324. PMID 24076589.
^ ^a ^b Scher HI, Beer TM, Higano CS, Taplin M, Efstathiou E, Anand A, Hung D, Hirmand M, Fleisher M (2009). "Antitumor activity of MDV3100 in a phase I/II study of castration-resistant prostate cancer (CRPC)". J Clin Oncol 27 (15s): abstr 5011.
^ Medivation, Inc. (2011-02-15). "Medivation and Astellas Announce Positive New, Long-Term Follow-Up Data From Phase 1-2 Trial of MDV3100 in Advanced Prostate Cancer Patients". Acquire Media. Retrieved 2011-03-24.
^ "NCT00974311". ClinicalTrials.gov, United States National Institutes of Health. Retrieved 2009-10-29. Safety and Efficacy Study of MDV3100 in Patients With Castration-Resistant Prostate Cancer Who Have Been Previously Treated With Docetaxel-based Chemotherapy (AFFIRM)
^ Scher HI, Fizazi K, Saad F, Taplin ME, Sternberg CN, Miller K, de Wit R, Mulders P, Chi KN, Shore ND, Armstrong AJ, Flaig TW, Fléchon A, Mainwaring P, Fleming M, Hainsworth JD, Hirmand M, Selby B, Seely L, de Bono JS (September 2012). "Increased survival with enzalutamide in prostate cancer after chemotherapy". N. Engl. J. Med. 367 (13): 1187–97. doi:10.1056/NEJMoa1207506. PMID 22894553.
^ Loftus P (2011-11-04). "Prostate Cancer Drug Shows Promise in Study". Health & Wellness. The Wall Street Journal. Retrieved 2011-11-04.
^ "NCT01212991". ClinicalTrials.gov, United States National Institutes of Health. Retrieved 2011-11-06. A Safety and Efficacy Study of Oral MDV3100 in Chemotherapy-Naive Patients With Progressive Metastatic Prostate Cancer (PREVAIL)
^ Medivation, Inc. (2013-10-22). "Medivation and Astellas Announce the Phase 3 PREVAIL Trial of Enzalutamide Meets Both Co-Primary Endpoints of Overall Survival and Radiographic Progression-Free Survival in Chemotherapy-Naive Patients With Advanced Prostate Cancer". Acquire Media. Retrieved 2013-11-10.
^ Medivation, Inc. (2011-03-30). "Medivation and Astellas Announce Initiation of Phase 2 Clinical Trial Comparing MDV3100 With Bicalutamide in Advanced Prostate Cancer". Press Release. Acquire Media. Retrieved 2011-04-02.
^ "NCT01288911". ClinicalTrials.gov, United States National Institutes of Health. Retrieved 2011-11-06. A Study of MDV3100 Versus Bicalutamide in Castrate Men With Metastatic Prostate Cancer
^ Payton, Sarah (2014). "Prostate cancer: Enzalutamide impresses in European studies". Nature Reviews Urology 11 (5): 243–243. doi:10.1038/nrurol.2014.98. ISSN 1759-4812.
^ ^a ^b ^c Golshayan AR, Antonarakis ES (2013). "Enzalutamide: an evidence-based review of its use in the treatment of prostate cancer". Core Evid 8: 27–35. doi:10.2147/CE.S34747. PMC 3622394. PMID 23589709.
^ Tombal, Bertrand; Borre, Michael; Rathenborg, Per; Werbrouck, Patrick; Van Poppel, Hendrik; Heidenreich, Axel; Iversen, Peter; Braeckman, Johan; Heracek, Jiri; Baskin-Bey, Edwina; Ouatas, Taoufik; Perabo, Frank; Phung, De; Baron, Benoit; Hirmand, Mohammad; Smith, Matthew R. (2015). "Long-term Efficacy and Safety of Enzalutamide Monotherapy in Hormone-naïve Prostate Cancer: 1- and 2-Year Open-label Follow-up Results". European Urology. doi:10.1016/j.eururo.2015.01.027. ISSN 0302-2838.
^ Vogelzang NJ (2012). "Enzalutamide--a major advance in the treatment of metastatic prostate cancer". N. Engl. J. Med. 367 (13): 1256–7. doi:10.1056/NEJMe1209041. PMID 23013078.
^ ^a ^b Wm Kevin Kelly; Edouard J. Trabulsi, MD; Nicholas G. Zaorsky, MD (17 December 2014). Prostate Cancer: A Multidisciplinary Approach to Diagnosis and Management. Demos Medical Publishing. pp. 342–. ISBN 978-1-936287-59-8.
^ Rathkopf, Dana; Scher, Howard I. (2013). "Androgen Receptor Antagonists in Castration-Resistant Prostate Cancer". The Cancer Journal 19 (1): 43–49. doi:10.1097/PPO.0b013e318282635a. ISSN 1528-9117.
^ Tan PS, Haaland B, Montero AJ, Kyriakopoulos CE, Lopes G (2014). "Hormonal Therapeutics Enzalutamide and Abiraterone Acetate in the Treatment of Metastatic Castration-Resistant Prostate Cancer (mCRPC) Post-docetaxel-an Indirect Comparison". Clin Med Insights Oncol 8: 29–36. doi:10.4137/CMO.S13671. PMC 3964205. PMID 24678245.
^ Crona DJ, Whang YE (2015). "Posterior reversible encephalopathy syndrome induced by enzalutamide in a patient with castration-resistant prostate cancer". Invest New Drugs 33 (3): 751–4. doi:10.1007/s10637-014-0193-3. PMID 25467090.
^ Richard J., Editor in Chief Hamilton FAAEM FACMT (4 December 2013). Tarascon Pocket Pharmacopoeia 2014 Deluxe Lab-Coat Edition. Jones & Bartlett Publishers. pp. 336–. ISBN 978-1-284-05399-9.

UpToDate Contents

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1. 去勢抵抗性前立腺癌：アンドロゲンの作用経路を標的する療法 castration resistant prostate cancer treatments targeting the androgen pathway
2. 播種性前立腺癌に対する治療の概要 overview of the treatment of disseminated prostate cancer
3. 去勢感受性前立腺癌の初期全身療法 initial systemic therapy for castration sensitive prostate cancer
4. 高齢者の前立腺癌 prostate cancer in elderly patients
5. 去勢抵抗性前立腺癌に対する免疫療法 immunotherapy for castration resistant prostate cancer

English Journal

Automated Bone Scan Index as a quantitative imaging biomarker in metastatic castration-resistant prostate cancer patients being treated with enzalutamide.

Anand A1,2, Morris MJ3,4, Larson SM4,5, Minarik D6, Josefsson A7, Helgstrand JT8, Oturai PS9, Edenbrandt L10, Røder MA8, Bjartell A11,12.
EJNMMI research.EJNMMI Res.2016 Dec;6(1):23. doi: 10.1186/s13550-016-0173-z. Epub 2016 Mar 9.
BACKGROUND: Having performed analytical validation studies, we are now assessing the clinical utility of the upgraded automated Bone Scan Index (BSI) in metastatic castration-resistant prostate cancer (mCRPC). In the present study, we retrospectively evaluated the discriminatory strength of the auto
PMID 26960325

ASC-J9(®) suppresses castration resistant prostate cancer progression via degrading the enzalutamide-induced androgen receptor mutant AR-F876L.

Wang R1, Lin W1, Lin C1, Li L1, Sun Y1, Chang C2.
Cancer letters.Cancer Lett.2016 Aug 28;379(1):154-60. doi: 10.1016/j.canlet.2016.05.018. Epub 2016 May 24.
Androgen deprivation therapy (ADT) with the newly developed powerful anti-androgen enzalutamide (Enz, also known as MDV3100) has promising therapeutic effects to suppress castration resistant prostate cancer (CRPC) and extending patients' lives an extra 4.8 months. However, most Enz therapy eventual
PMID 27233475

Design and synthesis of novel bicalutamide and enzalutamide derivatives as antiproliferative agents for the treatment of prostate cancer.

Bassetto M1, Ferla S2, Pertusati F1, Kandil S1, Westwell AD1, Brancale A1, McGuigan C1.
European journal of medicinal chemistry.Eur J Med Chem.2016 Aug 8;118:230-43. doi: 10.1016/j.ejmech.2016.04.052. Epub 2016 Apr 22.
Prostate cancer (PC) is one of the major causes of male death worldwide and the development of new and more potent anti-PC compounds is a constant requirement. Among the current treatments, (R)-bicalutamide and enzalutamide are non-steroidal androgen receptor antagonist drugs approved also in the ca
PMID 27131065

Japanese Journal

Enzalutamide versus abiraterone as a first-line endocrine therapy for castration-resistant prostate cancer (ENABLE study for PCa): A study protocol for a multicenter randomized phase III trial

BMC Cancer 17(1), 677, 2017-10-10
NAID 120006370938

エンザルタミド投与後に痙攣発作を認め不幸の転帰をとった去勢抵抗性前立腺癌の1例

泌尿器科紀要 = Acta urologica Japonica 63(10), 431-433, 2017-10
NAID 120006360776

Therapies for castration-resistant prostate cancer in a new era: The indication of vintage hormonal therapy, chemotherapy and the new medicines

International Journal of Urology 24(8), 566-572, 2017-08-01
NAID 120006334922

Related Pictures

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★リンクテーブル★

リンク元

「エンザルタミド」

Enzalutamide
Systematic (IUPAC) name
	4-(3-(4-Cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluoro-N-methylbenzamide
Clinical data
Trade names	Xtandi
AHFS/Drugs.com	entry
Licence data	US FDA:link
Pregnancy; category	US: X;
Legal status	US: ℞-only;
Routes of; administration	Oral
Pharmacokinetic data
Biological half-life	8–9 days
Identifiers
CAS Registry Number	915087-33-1
ATC code	L02BB04
PubChem	CID: 15951529
IUPHAR/BPS	6812
ChemSpider	13093347
UNII	93T0T9GKNU
ChEBI	CHEBI:68534
Chemical data
Formula	C21H16F4N4O2S
Molecular mass	464.44 g/mol
	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 ;

　　[★]

英: enzalutamide
商: イクスタンジ

[Litt2013-1] Jerome Z. Litt (25 January 2013). Litt's Drug Eruptions and Reactions Manual, 19th Edition. CRC Press. pp. 148–. ISBN 978-1-84214-599-9.

[urlMedivation.2C_Inc.-2] "Medivation's MDV3100 Shown to Be Effective in a Preclinical Model of Hormone-Refractory Prostate Cancer". Press release. Medivation, Inc. 2007-02-26. Retrieved 2009-05-10.

[url-3] "Medivation's MDV3100 Demonstrates Substantial PSA Reductions In First Patient Groups Treated In Phase 1-2 Hormone Refractory Prostate Cancer Trial". Medical News Today. 2007-11-06. Retrieved 2009-05-10.

[Cochrane_2012-4] "Preclinical Evaluation of Enzalutamide in Breast Cancer Models".

[url_MDV3100_Breast_Cancer_MarketWatch-5] "Medivation and Astellas Announce New Preclinical Study Results Showing MDV3100 Blocks Breast Cancer Cell Growth". Press Release. MarketWatch. 2011-08-04. Retrieved 2011-09-25.

[urlFDA_approves_new_treatment_for_a_type_of_late_stage_prostate_cancer-6] "FDA approves new treatment for a type of late stage prostate cancer". press release. United States Food and Drug Administration. 2012-08-31.

[7] Anna Azvolinsky (September 4, 2012). "FDA Approves Enzalutamide (Xtandi) for Late-Stage Prostate Cancer". CancerNetwork.

[8] Borman S (2008). "New prostate cancer agent class". Chemical & Engineering News 86 (38): 84–87. doi:10.1021/cen-v086n038.p084.

[pmid20218717-9] Jung ME, Ouk S, Yoo D, Sawyers CL, Chen C, Tran C, Wongvipat J (April 2010). "Structure-activity relationship for thiohydantoin androgen receptor antagonists for castration-resistant prostate cancer (CRPC)". J. Med. Chem. 53 (7): 2779–96. doi:10.1021/jm901488g. PMC 3180999. PMID 20218717.

[pmid19359544-10] Tran C, Ouk S, Clegg NJ, Chen Y, Watson PA, Arora V, Wongvipat J, Smith-Jones PM, Yoo D, Kwon A, Wasielewska T, Welsbie D, Chen CD, Higano CS, Beer TM, Hung DT, Scher HI, Jung ME, Sawyers CL (May 2009). "Development of a second-generation antiandrogen for treatment of advanced prostate cancer". Science 324 (5928): 787–90. doi:10.1126/science.1168175. PMC 2981508. PMID 19359544.

[pmid24076589-11] Antonarakis ES (2013). "Enzalutamide: The emperor of all anti-androgens". Transl Androl Urol 2 (2): 119–120. PMC 3785324. PMID 24076589.

[Scher_2009-12] Scher HI, Beer TM, Higano CS, Taplin M, Efstathiou E, Anand A, Hung D, Hirmand M, Fleisher M (2009). "Antitumor activity of MDV3100 in a phase I/II study of castration-resistant prostate cancer (CRPC)". J Clin Oncol 27 (15s): abstr 5011.

[url_Medivation_MDV3100_phase_1_2-13] Medivation, Inc. (2011-02-15). "Medivation and Astellas Announce Positive New, Long-Term Follow-Up Data From Phase 1-2 Trial of MDV3100 in Advanced Prostate Cancer Patients". Acquire Media. Retrieved 2011-03-24.

[ClinicalTrials.gov_NCT00974311-14] "NCT00974311". ClinicalTrials.gov, United States National Institutes of Health. Retrieved 2009-10-29. Safety and Efficacy Study of MDV3100 in Patients With Castration-Resistant Prostate Cancer Who Have Been Previously Treated With Docetaxel-based Chemotherapy (AFFIRM)

[Scher_2012-15] Scher HI, Fizazi K, Saad F, Taplin ME, Sternberg CN, Miller K, de Wit R, Mulders P, Chi KN, Shore ND, Armstrong AJ, Flaig TW, Fléchon A, Mainwaring P, Fleming M, Hainsworth JD, Hirmand M, Selby B, Seely L, de Bono JS (September 2012). "Increased survival with enzalutamide in prostate cancer after chemotherapy". N. Engl. J. Med. 367 (13): 1187–97. doi:10.1056/NEJMoa1207506. PMID 22894553.

[urlProstate_Cancer_Drug_Shows_Promise_in_Study_-_WSJ.com-16] Loftus P (2011-11-04). "Prostate Cancer Drug Shows Promise in Study". Health & Wellness. The Wall Street Journal. Retrieved 2011-11-04.

[ClinicalTrials.gov_PREVAIL-17] "NCT01212991". ClinicalTrials.gov, United States National Institutes of Health. Retrieved 2011-11-06. A Safety and Efficacy Study of Oral MDV3100 in Chemotherapy-Naive Patients With Progressive Metastatic Prostate Cancer (PREVAIL)

[url_Medivation_enzalutamide_phase_3_PREVAIL-18] Medivation, Inc. (2013-10-22). "Medivation and Astellas Announce the Phase 3 PREVAIL Trial of Enzalutamide Meets Both Co-Primary Endpoints of Overall Survival and Radiographic Progression-Free Survival in Chemotherapy-Naive Patients With Advanced Prostate Cancer". Acquire Media. Retrieved 2013-11-10.

[url_Medivation_MDV3100_vs_bicalutamide-19] Medivation, Inc. (2011-03-30). "Medivation and Astellas Announce Initiation of Phase 2 Clinical Trial Comparing MDV3100 With Bicalutamide in Advanced Prostate Cancer". Press Release. Acquire Media. Retrieved 2011-04-02.

[ClinicalTrials.gov_NCT01288911-20] "NCT01288911". ClinicalTrials.gov, United States National Institutes of Health. Retrieved 2011-11-06. A Study of MDV3100 Versus Bicalutamide in Castrate Men With Metastatic Prostate Cancer

[Payton2014-21] Payton, Sarah (2014). "Prostate cancer: Enzalutamide impresses in European studies". Nature Reviews Urology 11 (5): 243–243. doi:10.1038/nrurol.2014.98. ISSN 1759-4812.

[pmid23589709-22] Golshayan AR, Antonarakis ES (2013). "Enzalutamide: an evidence-based review of its use in the treatment of prostate cancer". Core Evid 8: 27–35. doi:10.2147/CE.S34747. PMC 3622394. PMID 23589709.

[TombalBorre2015-23] Tombal, Bertrand; Borre, Michael; Rathenborg, Per; Werbrouck, Patrick; Van Poppel, Hendrik; Heidenreich, Axel; Iversen, Peter; Braeckman, Johan; Heracek, Jiri; Baskin-Bey, Edwina; Ouatas, Taoufik; Perabo, Frank; Phung, De; Baron, Benoit; Hirmand, Mohammad; Smith, Matthew R. (2015). "Long-term Efficacy and Safety of Enzalutamide Monotherapy in Hormone-naïve Prostate Cancer: 1- and 2-Year Open-label Follow-up Results". European Urology. doi:10.1016/j.eururo.2015.01.027. ISSN 0302-2838.

[pmid23013078-24] Vogelzang NJ (2012). "Enzalutamide--a major advance in the treatment of metastatic prostate cancer". N. Engl. J. Med. 367 (13): 1256–7. doi:10.1056/NEJMe1209041. PMID 23013078.

[KellyMD2014-25] Wm Kevin Kelly; Edouard J. Trabulsi, MD; Nicholas G. Zaorsky, MD (17 December 2014). Prostate Cancer: A Multidisciplinary Approach to Diagnosis and Management. Demos Medical Publishing. pp. 342–. ISBN 978-1-936287-59-8.

[RathkopfScher2013-26] Rathkopf, Dana; Scher, Howard I. (2013). "Androgen Receptor Antagonists in Castration-Resistant Prostate Cancer". The Cancer Journal 19 (1): 43–49. doi:10.1097/PPO.0b013e318282635a. ISSN 1528-9117.

[pmid24678245-27] Tan PS, Haaland B, Montero AJ, Kyriakopoulos CE, Lopes G (2014). "Hormonal Therapeutics Enzalutamide and Abiraterone Acetate in the Treatment of Metastatic Castration-Resistant Prostate Cancer (mCRPC) Post-docetaxel-an Indirect Comparison". Clin Med Insights Oncol 8: 29–36. doi:10.4137/CMO.S13671. PMC 3964205. PMID 24678245.

[pmid25467090-28] Crona DJ, Whang YE (2015). "Posterior reversible encephalopathy syndrome induced by enzalutamide in a patient with castration-resistant prostate cancer". Invest New Drugs 33 (3): 751–4. doi:10.1007/s10637-014-0193-3. PMID 25467090.

[FACMT2013-29] Richard J., Editor in Chief Hamilton FAAEM FACMT (4 December 2013). Tarascon Pocket Pharmacopoeia 2014 Deluxe Lab-Coat Edition. Jones & Bartlett Publishers. pp. 336–. ISBN 978-1-284-05399-9.

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enzalutamide