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01-09-2017 | Review Article

GnRH Antagonist: a New and an Effective Way of Treatment of Advanced Prostate Cancer

Authors: Bertrand Tomabal, S.K Raghunath, N Srivatsa, V.H Nagaraj

Published in: Indian Journal of Surgical Oncology | Issue 3/2017

Abstract

Castration remains the mainstay of treatment in the management of metastatic prostate cancer. Medical castration plays an important role in a majority of these patients. Gonadotropin releasing hormone (GnRH) agonists have been commonly used hitherto to achieve medical castration. Arrival of GnRH antagonists have opened a new approach in the management of these patients with distinct drug-related and cancer-related benefits including prevention of microsurges and reduction in cardiovascular complications. This article elucidates the mechanism of action of GnRH antagonists along with its clinical advantages and demerits.

Persson BE, Kold Olesen T, Jensen JK (2009) Degarelix: a new approach for the treatment of prostate cancer. Neuroendocrinology 90(3):235–244. doi:10.1159/000228832 CrossRefPubMed

Shore ND (2013) Experience with degarelix in the treatment of prostate cancer. Ther Adv Urol 5(1):11–24. doi:10.1177/ 1756287212461048 CrossRefPubMedPubMedCentral

Carter NJ, Keam SJ (2014) Degarelix: a review of its use in patients with prostate cancer. Drugs 74:699–712. doi:10.1007/s40265-014-0211-y CrossRefPubMed

Engel JB, Schally AV (2007) Drug insight: clinical use of agonists and antagonists of luteinizing-hormone-releasing hormone. Nat Clin Pract Endocrinol Metab 3(2):157–167. doi:10.1038/ncpendmet0399 CrossRefPubMed

Frampton J, Lyseng-Williamson K (2009) Degarelix. Drugs 69:1967–1976. doi:10.2165/10484080-000000000-00000 CrossRefPubMed

Pinski J, Yano T, Miller G, Schally AV (1992) Blockade of the LH response induced by the agonist D-Trp-6-LHRH in rats by a highly potent LH-RH antagonist SB-75. Prostate 20(3):213–224CrossRefPubMed

Sharma OP, Weinbauer GF, Behre HM, Nieschlag E (1992) The gonadotropin-releasing hormone (GnRH) agonist-induced initial rise of bioactive LH and testosterone can be blunted in a dose-dependent manner by GnRH antagonist in the non-human primate. Urol Res 20(5):317–321CrossRefPubMed

Broqua P, Riviere PJ, Conn PM, Rivier JE, Aubert ML, Junien JL (2002) Pharmacological profile of a new, potent, and long-acting gonadotropin-releasing hormone antagonist: degarelix. J Pharmacol Exp Ther 301(1):95–102. doi:10.1124/jpet.301.1.95 CrossRefPubMed

Van Poppel H, Tombal B, de la Rosette JJ, Persson BE, Jensen JK, Kold Olesen T (2008) Degarelix: a novel gonadotropin-releasing hormone (GnRH) receptor blocker—results from a 1-yr, multicentre, randomised, phase 2 dosage-finding study in the treatment of prostate cancer. Eur Urol 54(4):805–813. doi:10.1016/j.eururo.2008.04.065 CrossRefPubMed

10.

Gittelman M, Pommerville PJ, Persson BE, Jensen JK, Olesen TK (2008) Degarelix study group. A 1-year, open label, randomized phase II dose finding study of degarelix for the treatment of prostate cancer in North America. J Urol 180(5):1986–1992. doi:10.1016/j.juro.2008.07.033 CrossRefPubMed

11.

Ozono S, Ueda T, Hoshi S et al (2012) The efficacy and safety of degarelix, a GnRH antagonist: a 12-month, multicentre, randomized, maintenance dose-finding phase II study in Japanese patients with prostate cancer. Jpn J Clin Oncol 42(6):477–484. doi:10.1093/jjco/hys035 CrossRefPubMed

12.

Klotz L, Boccon-Gibod L, Shore ND et al (2008) The efficacy and safety of degarelix: a 12-month, comparative, randomized, open-label, parallel-group phase III study in patients with prostate cancer. BJU Int 102(11):1531–1538. doi:10.1111/j.1464-410X.2008.08183.x CrossRefPubMed

13.

Crawford ED, Shore ND, Moul JW et al (2014) Long term tolerability and efficacy of degarelix: 5-year results from a phase III extension trial with a one-arm crossover from leuprolide to degarelix. Urology 83(5):1122–1128. doi:10.1016/j.urology.2014.01.013 CrossRefPubMed

14.

de la Rosette J, Davis R 3rd, Frankel D, Kold Olesen T (2011) Efficacy and safety of androgen deprivation therapy after switching from monthly leuprolide to monthly degarelix in patients with prostate cancer. Int J Clin Pract 65(5):559–566. doi:10.1111/j.1742-1241.2011.02637.x CrossRefPubMed

15.

Smith M, Klotz L, Persson B, Olesen T, Wilde A (2010) Cardiovascular safety of degarelix: results from a 12-month, comparative, randomized, open label, parallel-group phase III trial in patients with prostate cancer. J Urol 184:2313–2319. doi:10.1016/j.juro.2010.08.012 CrossRefPubMedPubMedCentral

16.

Smith M, Klotz L, van der Meulen E, Colli E, Tankó L (2011) Gonadotropin-releasing hormone blockers and cardiovascular disease risk: analyses of prospective clinical trials of degarelix. J Urol 186:1835–1842. doi:10.1016/j.juro.2011.07.035 CrossRefPubMedPubMedCentral

17.

Albertsen PC, Klotz L, Tombal B et al (2014) Cardiovascular morbidity associated with gonadotrophin releasing hormone agonists and an antagonist. Eur Urol 65(3):565–573. doi:10.1016/j.eururo.2013.10.032 CrossRefPubMed

Title: GnRH Antagonist: a New and an Effective Way of Treatment of Advanced Prostate Cancer
Authors: Bertrand Tomabal
S.K Raghunath
N Srivatsa
V.H Nagaraj
Publication date: 01-09-2017
Publisher: Springer India
Published in: Indian Journal of Surgical Oncology / Issue 3/2017
Print ISSN: 0975-7651
Electronic ISSN: 0976-6952
DOI: https://doi.org/10.1007/s13193-016-0611-4

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GnRH Antagonist: a New and an Effective Way of Treatment of Advanced Prostate Cancer

Abstract

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Abstract

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