Pharmacological Review On Enzalutamide

Year : 2024 | Volume :11 | Issue : 02 | Page : 7-15
By

Sreelatha Gangu,

Mahaboobi,

Sruthi Katta,

Megavath Subhash,

Narender Boggula,

Rama Rao Tadikonda,

  1. Associate Professor Department of Pharmaceutical Analysis, CMR College of Pharmacy Telangana India
  2. Research Scholar Department of Pharmacy, CMR College of Pharmacy, Hyderabad, Telangana India
  3. Research Scholar Department of Pharmacy, CMR College of Pharmacy, Hyderabad, Telangana India
  4. Research Scholar Department of Pharmaceutical Analysis, CMR College of Pharmacy Telangana India
  5. Associate Professor Department of Pharmaceutical Analysis, CMR College of Pharmacy Telangana India
  6. Principal CMR College of Pharmacy Telangana India

Abstract

A key therapeutic option in the treatment of prostate cancer, especially metastatic castration-resistant prostate cancer (mCRPC), is Enzalutamide, a second-generation anti androgen drug. Enzalutamide, discovered by Charles Sawyer and Michael Jung at the University of California, Los Angeles, was developed and FDA-approved in 2012. Its therapeutic significance was further solidified with subsequent extensions in indications to encompass metastatic castration-sensitive prostate cancer and non-metastatic castration-resistant prostate cancer. Enzalutamide’s crystalline structure and restricted water solubility are two of its physical and chemical characteristics that highlight its formulation and pharmacological implications. Enzalutamide pharmacologically inhibits the binding of dihydro testosterone to the androgen receptor in a competitive manner, hence hindering the progression of cancer. It is mostly metabolized in the liver, where it produces active metabolites that are mainly excreted in faces. Its effectiveness in improving overall survival, especially in high-risk patients, has been demonstrated in clinical trials. Although Enzalutamide has many therapeutic advantages, it also has several noticeable side effects, such as gynecomastia, exhaustion, and seizures. In addition, there are very few cases of CNS adverse effects, such as posterior reversible encephalopathy syndrome (PRES). As a result, close observation is necessary, particularly in those who already have seizure disorders. All things considered, Enzalutamide is a mainstay of the treatment of prostate cancer, providing patients with better results and a higher quality of life at different stages of the disease.

Keywords: Enzalutamide, Prostate cancer, Androgens, Gynecomastia, Metabolites

[This article belongs to Trends in Drug Delivery(tdd)]

How to cite this article: Sreelatha Gangu, Mahaboobi, Sruthi Katta, Megavath Subhash, Narender Boggula, Rama Rao Tadikonda. Pharmacological Review On Enzalutamide. Trends in Drug Delivery. 2024; 11(02):7-15.
How to cite this URL: Sreelatha Gangu, Mahaboobi, Sruthi Katta, Megavath Subhash, Narender Boggula, Rama Rao Tadikonda. Pharmacological Review On Enzalutamide. Trends in Drug Delivery. 2024; 11(02):7-15. Available from: https://journals.stmjournals.com/tdd/article=2024/view=149591



References

  1. Tran C, Ouk S, Clegg NJ, Chen Y, Watson PA, Arora V, Wongvipat J, Smith-Jones PM, Yoo D, Kwon A, Wasielewska T. Development of a second-generation antiandrogen for treatment of advanced prostate cancer. Science. 2009 May 8;324(5928):787-90.
  2. Beer TM, Armstrong AJ, Rathkopf DE, Loriot Y, Sternberg CN, Higano CS, Iversen P, Bhattacharya S, Carles J, Chowdhury S, Davis ID. Enzalutamide in metastatic prostate cancer before chemotherapy. New England Journal of Medicine. 2014 Jul 31;371(5):424-33.
  3. Scher HI, Fizazi K, Saad F, Taplin ME, Sternberg CN, Miller K, De Wit R, Mulders P, Chi KN, Shore ND, Armstrong AJ. Increased survival with enzalutamide in prostate cancer after chemotherapy. New England Journal of Medicine. 2012 Sep 27;367(13):1187-97.
  4. Benoist GE, Hendriks RJ, Mulders PF, Gerritsen WR, Somford DM, Schalken JA, van Oort IM, Burger DM, van Erp NP. Pharmacokinetic Aspects of the Two Novel Oral Drugs Used for Metastatic Castration-Resistant Prostate Cancer: Abiraterone Acetate and Enzalutamide. Clin Pharmacokinetic. 2016; 55(11):1369-1380.
  5. Fujita K, Nonomura N. Role of Androgen Receptor in Prostate Cancer: A Review. World J Mens Health. 2019; 37(3):288-295.
  6. Schalken J, Fitzpatrick JM. Enzalutamide: targeting the androgen signalling pathway in metastatic castration-resistant prostate cancer. BJU Int. 2016; 117(2):215-225.
  7. Menon MP, Higano CS. Enzalutamide, a second-generation androgen receptor antagonist: development and clinical applications in prostate cancer. Curr Oncol Rep. 2013; 15(2):69-75.
  8. Foster WR, Car BD, Shi H, Levesque PC, Obermeier MT, Gan J, Arezzo JC, Powlin SS, Dinchuk JE, Balog A, Salvati ME, Attar RM, Gottardis MM. Drug safety is a barrier to the discovery and development of new androgen receptor antagonists. Prostate. 2011; 71(5):480-488.
  9. Keating GM. Enzalutamide: a review of its use in chemotherapy-naïve metastatic castration-resistant prostate cancer. Drugs & Aging. 2015; 32(3):243–249.
  10. Weber GF. (2015b). Molecular therapies of cancer. In Springer eBooks, USA.
  11. Borman S. New prostate cancer agent class. Chemical & Engineering News. 2008; 86(38):84–87.
  12. Jung ME, Ouk S, Yoo D, Sawyers CL, Chen C, Tran C, Wongvipat J. Structure-activity relationship for thiohydantoin androgen receptor antagonists for castration-resistant prostate cancer (CRPC). J Med Chem. 2010; 53(7):2779-2796.
  13. Narayanan R, Coss CC, Dalton JT. Development of selective androgen receptor modulators (SARMs). Mol Cell Endocrinol. 2018; 465:134-142.
  14. FDA approves Enzalutamide for metastatic castration-sensitive prostate cancer. U.S. Food and Drug Administration(FDA). 17 December 2019.
  15. Liu B, Su L, Geng J, Liu J, Zhao G. Developments in nonsteroidal antiandrogens targeting the androgen receptor. Chem Med Chem. 2010; 5(10): 1651–1661.
  16. Swe NC, Ahmed S, Eid M, Poretsky L, Gianos E, Cusano NE. The effects of gender-affirming hormone therapy on cardiovascular and skeletal health: a literature review. Metabolism Open. 2022; 13:100173.
  17. Tyler Marciniak. Enzalutamide Phase 2 terrain trial demonstrated statistically significant increase in PFS As Compared to Bicalutamide in Metastatic Prostate Cancer. 2015; (847) 736-7145.
  18. Pan F, Reifsnider O, Zheng Y, Proskorovsky I, Li T, He J, et al. Modeling Clinical Outcomes in Prostate Cancer: Application and Validation of the Discrete Event Simulation Approach. Value in Health. 2018; 21(4):416–22.
  19. Medivation’s MDV3100 shown to be effective in a preclinical model of hormone-refractory prostate cancer. Reuters, 2007.
  20. Research C for DE and. FDA approves enzalutamide for castration-resistant prostate cancer. FDA. 2018.
  21. Research C for DE and. FDA approves talazoparib with enzalutamide for HRR gene-mutated metastatic castration-resistant prostate cancer. FDA. 2023.
  22. Scher HI, Beer TM, Higano CS, et al. Antitumour activity of MDV3100 in castration-resistant prostate cancer: a phase 1–2 study. Lancet, 2010; 375:1437–1446.
  23. Gibbons JA, Ouatas T, Krauwinkel W, Ohtsu Y, van der Walt JS, Beddo V, de Vries M, Mordenti J. Clinical Pharmacokinetic Studies of Enzalutamide. Clin Pharmacokinet. 2015; 54(10):1043-1055.
  24. Sadar MD. Advances in small molecule inhibitors of androgen receptor for the treatment of advanced prostate cancer. World J Urol. 2012; 30(3):311–318
  25. Li JJ, Johnson DS (14 December 2015). Chapter 6: Enzalutamide. Innovative Drug Synthesis. John Wiley & Sons. p.103.
  26. Ricci F, Buzzatti G, Rubagotti A, Boccardo F (November 2014). Safety of antiandrogen therapy for treating prostate cancer. Expert Opinion on Drug Safety. 13 (11): 1483–1499.
  27. Claessens F, Helsen C, Prekovic S, Van den Broeck T, Spans L, Van Poppel H, et al. (December 2014). Emerging mechanisms of enzalutamide resistance in prostate cancer. Nature Reviews Urology. 11 (12): 712–716.
  28. Balbas MD, Evans MJ, Hosfield DJ, Wongvipat J, Arora VK, Watson PA, Chen Y, Greene GL, Shen Y, Sawyers CL. Overcoming mutation-based resistance to antiandrogens with rational drug design. Elife. 2013 Apr 9; 2:e00499.
  29. Pekovic S, van Royen ME, Voet AR, Geverts B, Houtman R, Melchers D, et al. (May 2016). The effect of F877L and T878A mutations on androgen receptor response to Enzalutamide. Molecular Cancer Therapeutics. 15 (7): 1702–12.
  30. Antonarakis ES, Lu C, Wang H, Luber B, Nakazawa M, Roeser JC, et al. (September 2014). AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer. New EnglandJournalof Medicine. 371 (11): 1028–1038.
  31. Arora VK, Schenkein E, Murali R, Subudhi SK, Wongvipat J, Balbas MD, et al. (December 2013). Glucocorticoid receptor confers resistance to antiandrogens by bypassing androgen receptorblockade. Cell. 155 (6):130922.
  32. Cui Y, Nadiminty N, Liu C, Lou W, Schwartz CT, Gao AC (June 2014). Upregulation of glucose metabolism by NF-B2/p52 mediates Enzalutamide resistance in castration-resistant prostate cancer cells. Endocrine-Related Cancer. 21 (3): 435–442.
  33. Nguyen HG, Yang JC, Kung HJ, Shi XB, Tilki D, Lara PN, et al. (September 2014). Targeting autophagy overcomes Enzalutamide resistance in castration-resistant prostate cancer cells and improves therapeutic response in a xenograft model. Oncogene. 33 (36): 4521–4530.
  34. Kim TH, Jeong JW, Song JH, Lee KR, Ahn S, Ahn SH, et al. (November 2015). Pharmacokinetics of Enzalutamide, an anti-prostate cancer drug, in rats. Archives of Pharmacal Research. 38 (11): 2076–2082
  35. Wenzel M, Nocera L, Collà Ruvolo C, Würnschimmel C, Tian Z, Shariat SF, et al. (May 2021). “Overall survival and adverse events after treatment with darolutamide vs. apalutamide vs. enzalutamide for high-risk non-metastatic castration-resistant prostate cancer: a systematic review and network meta-analysis”. Prostate Cancer Prostatic Dis (Systematic review). 25 (2): 139–148.
  36. Advanced Prostate Cancer Treatment | XTANDI® (enzalutamide) Safety Info Available from: https://www.xtandi.com/
  37. Antonarakis ES (June 2013). “Enzalutamide: The emperor of all anti-androgens”. Translational Andrology and Urology. 2 (2): 119–120.
  38. Tombal B, Borre M, Rathenborg P, Werbrouck P, Van Poppel H, Heidenreich A, Iversen P, Braeckman J, Heracek J, Baskin-Bey E, Ouatas T. Long-term efficacy and safety of enzalutamide monotherapy in hormone-naïve prostate cancer: 1-and 2-year open-label follow-up results. European urology. 2015 1; 68(5):787-94.
  39. Desai C. Meyler’s side effects of drugs: The international encyclopaedia of adverse drug reactions and interactions. Indian J Pharmacol. 2016; 48(2):224.
  40. Alex AB, Pal SK, Agarwal N. CYP17 inhibitors in prostate cancer: latest evidence and clinical potential. Ther Adv Med Oncol. 2016; 8(4):267-275.
  41. Rathkopf D, Scher HI. Androgen receptor antagonists in castration-resistant prostate cancer. Cancer J. 2013; 19(1):43-49.
  42. Litt JZ. Comprar Litt’s Drug Eruptions and Reactions Manual, | Jerome Z. Litt| 9781842145982| Informa Healthcare. Litt’s Drug Eruptions and Reactions Manual, 19th edn, 2013.
  43. Tan PS, Haaland B, Montero AJ, Kyriakopoulos CE, Lopes G. 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. 2014; 8:29-36
  44. Bonder, B., & De Lima, M. (2019). Posterior reversible encephalopathy syndrome (PRES) in cancer patients. In Springer eBooks(pp. 353–365).

Regular Issue Subscription Review Article
Volume 11
Issue 02
Received April 8, 2024
Accepted May 10, 2024
Published May 15, 2024