Abiraterone or Enzalutamide in CRPC After Chemotherapy

  • U-Syn HaEmail author


Most prostate cancer patients treated with androgen deprivation therapy (ADT) as systemic therapy will develop castration-resistant prostate cancer (CRPC). CRPC is most frequently characterized by a rise in serum prostate-specific antigen (PSA) levels over time in the context of low (< 50 ng/mL) serum testosterone levels. Expression of PSA is typically regulated by the androgen receptor (AR), supporting a role for AR in CRPC. The biological significance of CRPC is that an important mechanism of CRPC is the upregulation of intracellular androgen and/or androgen receptor (AR), leading to sustained AR-directed growth of prostate cancer despite a castrate level of serum androgens [1]. Thus, patients with CRPC are usually sensitive to sequential “secondary” hormonal therapies directed at AR inhibition. The treatment landscape for CRPC has expanded in the past decade to include several novel agents. These novel therapies have been directed specifically against CRPC, including abiraterone acetate (AA) and enzalutamide [2, 3]. The recent US Food and Drug Administration (FDA)-approved enzalutamide (Xtandi) and abiraterone (Xytiga) based on researches showed improvement of survival in the treatment for CRPC after chemotherapy. The present article reviews recent advances of the novel AR-targeted therapeutic agents for CRPC.


  1. 1.
    Montgomery RB, Mostaghel EA, Vessella R, Hess DL, Kalhorn TF, Higano CS, et al. Maintenance of intratumoral androgens in metastatic prostate cancer: a mechanism for castration-resistant tumor growth. Cancer Res. 2008;68(11):4447–54.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    de Bono JS, Logothetis CJ, Molina A, Fizazi K, North S, Chu L, et al. Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med. 2011;364(21):1995–2005.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Ryan CJ, Smith MR, de Bono JS, Molina A, Logothetis CJ, de Souza P, et al. Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med. 2013;368(2):138–48.CrossRefPubMedGoogle Scholar
  4. 4.
    Tran C, Ouk S, Clegg NJ, Chen Y, Watson PA, Arora V, et al. Development of a second-generation antiandrogen for treatment of advanced prostate cancer. Science (New York, NY). 2009;324(5928):787–90.CrossRefGoogle Scholar
  5. 5.
    Guerrero J, Alfaro IE, Gomez F, Protter AA, Bernales S. Enzalutamide, an androgen receptor signaling inhibitor, induces tumor regression in a mouse model of castration-resistant prostate cancer. Prostate. 2013;73(12):1291–305.CrossRefPubMedGoogle Scholar
  6. 6.
    El-Amm J, Patel N, Freeman A, Aragon-Ching JB. Metastatic castration-resistant prostate cancer: critical review of enzalutamide. Clin Med Insights Oncol. 2013;7:235–45.PubMedPubMedCentralGoogle Scholar
  7. 7.
    Scher HI, Fizazi K, Saad F, Taplin ME, Sternberg CN, Miller K, et al. Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med. 2012;367(13):1187–97.CrossRefPubMedGoogle Scholar
  8. 8.
    Zhang T, Zhu J, George DJ, Armstrong AJ. Enzalutamide versus abiraterone acetate for the treatment of men with metastatic castration-resistant prostate cancer. Expert Opin Pharmacother. 2015;16(4):473–85.CrossRefPubMedGoogle Scholar
  9. 9.
    Mostaghel EA. Abiraterone in the treatment of metastatic castration-resistant prostate cancer. Cancer Manag Res. 2014;6:39–51.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Locke JA, Wasan KM, Nelson CC, Guns ES, Leon CG. Androgen-mediated cholesterol metabolism in LNCaP and PC-3 cell lines is regulated through two different isoforms of acyl-coenzyme A:Cholesterol Acyltransferase (ACAT). Prostate. 2008;68(1):20–33.CrossRefPubMedGoogle Scholar
  11. 11.
    Efstathiou E, Titus M, Tsavachidou D, Tzelepi V, Wen S, Hoang A, et al. Effects of abiraterone acetate on androgen signaling in castrate-resistant prostate cancer in bone. J Clin Oncol Off J Am Soc Clin Oncol. 2012;30(6):637–43.CrossRefGoogle Scholar
  12. 12.
    Li R, Evaul K, Sharma KK, Chang KH, Yoshimoto J, Liu J, et al. Abiraterone inhibits 3beta-hydroxysteroid dehydrogenase: a rationale for increasing drug exposure in castration-resistant prostate cancer. Clin Cancer Res. 2012;18(13):3571–9.CrossRefPubMedGoogle Scholar
  13. 13.
    Reid AH, Attard G, Danila DC, Oommen NB, Olmos D, Fong PC, et al. Significant and sustained antitumor activity in post-docetaxel, castration-resistant prostate cancer with the CYP17 inhibitor abiraterone acetate. J Clin Oncol Off J Am Soc Clin Oncol. 2010;28(9):1489–95.CrossRefGoogle Scholar
  14. 14.
    Danila DC, Morris MJ, de Bono JS, Ryan CJ, Denmeade SR, Smith MR, et al. Phase II multicenter study of abiraterone acetate plus prednisone therapy in patients with docetaxel-treated castration-resistant prostate cancer. J Clin Oncol Off J Am Soc Clin Oncol. 2010;28(9):1496–501.CrossRefGoogle Scholar
  15. 15.
    Fizazi K, Scher HI, Molina A, Logothetis CJ, Chi KN, Jones RJ, et al. Abiraterone acetate for treatment of metastatic castration-resistant prostate cancer: final overall survival analysis of the COU-AA-301 randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol. 2012;13(10):983–92.CrossRefPubMedGoogle Scholar
  16. 16.
    Kang M, Jeong CW, Kwak C, Ku JH, Kim HH. Comparing the clinical efficacy of abiraterone acetate, enzalutamide, and orteronel in patients with metastatic castration-resistant prostate cancer by performing a network meta-analysis of eight randomized controlled trials. Oncotarget. 2017;8(35):59690–7.CrossRefPubMedPubMedCentralGoogle Scholar

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© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  1. 1.Department of Urology, College of MedicineThe Catholic University of KoreaSeoulSouth Korea

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