Luteinizing hormone-releasing hormone antagonists in patients with prostate cancer. A standard approach and the results of innovative studies

Prostate cancer (PC) is one of the most burning problems of modern urologic oncology. Hormonal therapy (HT) using medical castration
remains a basic therapy for metastatic PC. HT with a novel class of luteinizing hormone-releasing hormone (LHRH) receptor antagonists is
a promising and effective castration treatment option that has a number of significant advantages over LHRH analogues. The paper reviews the results of trials comparing the efficiency and adverse reactions of HT using LHRH antagonists and analogues and gives those of a Russian multicenter study covering the countrywide experience with degarelix.

1. Состояние онкологической помощи населению России в 2012 году. Под ред. А.Д. Каприна, В.В. Старинского, Г.В. Петровой. М., 2013.

2. Huggins C., Hoges C.V. Studies on prostate cancer. The effect of castration. Cancer Res 1941:385–402.

3. Malkowicz S.B. The role of diethylstilbestrol in the treatment of prostate cancer. Urology 2001;58(2 Suppl 1):108–13.

4. Kaisary A.V., Tyrrell C.J., Peeling W.B. et al. Comparison of LHRH analogue with orchiectomy in patients with metastatic prostatic carcinoma. Br J Urol 1991;67(5):502–8.

5. Keating N.L., O'Malley A.J., Freedland S.J. et al. Diabetes and cardiovascular disease during androgen deprivation therapy: observational study of veterans with prostate cancer. JNCI J Natl Cancer Inst 2010;102:39–46.

6. Bubley G.J. Is the flare phenomenon clinically significant? Urology 2001;58 (2 Suppl 1):5–9.

7. Bertaglia V., Tucci M., Fiori C. et al. Effects of serum testosterone levels after 6 months of androgen deprivation therapy on the outcome of patients with prostate cancer. Clin Genitourin Cancer 2013;11(3):325–30.

8. Rick F.G., Block N.L., Schally A.V. An update on the use of degarelix in the treatment of advanced hormone-dependent prostate cancer. Onco Targets Ther 2013;6:391–402.

9. Anderson J. Degarelix: a novel gonadotropin-releasing hormone blocker for the treatment of prostate cancer. Future Oncol 2009;5(4):433–43.

10. Persson B.E., Kold Olesen T., Jensen J.K. Degarelix: a new approach for the treatment of prostate cancer. Neuroendocrinology 2009;90(3):235–44.

11. Klotz L., Boccon-Gibod L., Shore N.D. et al. The efficacy and safety of degarelix: a 12-month, comparative, randomized, openlabel, parallel-group phase III study in patients with prostate cancer. BJU Int 2008;102(11):1531–8.

12. Crawford E.D., Shore N.D., Moul J.W. et al. Long-term tolerability and efficacy of degarelix: 5-year results from a phase III extension trial with a 1-arm crossover from leuprolide to degarelix. Urology 2014;83(5):1122–8.

13. Klotz L., Miller K., Crawford E.D. et al. Disease control outcomes from analysis of pooled individual patient data from five comparative randomised clinical trials of degarelix versus luteinising hormonereleasing hormone agonists. Eur Urol 2014 Jan 9. pii: S0302–2838(13)01491–7.

14. Miller K., Rüssel C., Goble S. et al. Open-label, exploratory study of degarelix as second-line hormonal therapy in patients with prostate cancer (CS27). EAU 2013; Poster 678.

15. Van Poppel H., Klotz L. Gonadotropinreleasing hormone: an update review of the antagonists versus agonists. Int J Urol 2012;19(7):594–601.

16. Smith M.R., Klotz L., van der Meulen E. et al. Gonadotropin-releasing hormone blockers and cardiovascular disease risk: analysis of prospective clinical trials of degarelix. J Urol 2011;186(5): 1835–42.

17. Tanriverdi F., Gonzalez-Martinez D., Hu Y. et al. GnRH-I and GnRH-II have differential modulatory effects on human peripheral blood mononuclear cell proliferation and interleukin-2 receptor gamma-chain mRNA expression in healthy males. Clin Exp Immunol 2005;142(1):103–10.

18. Chen H.F., Jeung E.B., Stephenson M., Leung P.C. Human peripheral blood mononuclear cells express gonadotropinreleasing hormone (GnRH), GnRH receptor, and interleukin-2 receptor gamma-chain messenger ribonucleic acids that are regulated by GnRH in vitro. J Clin Endocrinol Metab 1999;84(2):743–50.