Current and emerging gonadotropin-releasing hormone (GnRH) antagonists for the treatment of prostate cancer

References

• Bolla M, Van Tienhoven G, Warde P, et al. External irradiation with or without long-term androgen suppression for prostate cancer with high metastatic risk: 10-year results of an EORTC randomised study. Lancet Oncol. 2010;Nov;11(11):1066–1073.
   PubMed Web of Science ®Google Scholar
• Dellis A, Papatsoris A. Therapeutic outcomes of the LHRH antagonists. Expert Rev Pharmacoecon Outcomes Res. 2017 Oct;17(5):481–488.
   PubMed Web of Science ®Google Scholar
• Shore ND, Saad F, Cookson MS, et al. HERO study investigators. oral relugolix for androgen-deprivation therapy in advanced prostate cancer. N Engl J Med. 2020 Jun 4;382(23):2187–2196.
   PubMed Web of Science ®Google Scholar
• Huggins C, Hodges CV. Studies on prostatic cancer: i. The effect of castration, of estrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate. J Urol. 1941;168:9–12.
   Web of Science ®Google Scholar
• Ryan CJ, Tindall DJ. Androgen receptor rediscovered: the new biology and targeting the androgen receptor therapeutically. J Clin Onc. 2011;29(27):3651–3658.
   PubMed Web of Science ®Google Scholar
• Engel JB, Schally AV. Drug insight: clinical use of agonists and antagonists of luteinizing-hormone-releasing hormone. Nat Clin Pract Endocrinol Metab. 2007;3:157–167.
   PubMedGoogle Scholar
• Van Poppel H, Nilsson S. Testosterone surge: rationale for gonadotropin-releasing hormone blockers? Urology. 2008;71:1001–1006.
   PubMed Web of Science ®Google Scholar
• Crawford ED, Tombal B, Miller K, et al. A phase III extension trial with a 1-arm crossover from leuprolide to degarelix: comparison of gonadotropin-releasing hormone agonist and antagonist effect on prostate cancer. J Urol. 2011;186:889–897.
   PubMed Web of Science ®Google Scholar
• Frampton JE, Lyseng-Williamson KA. Degarelix. Drugs. 2009;69(14):1967–1976.
   PubMed Web of Science ®Google Scholar
• Garnick MD, Campion M. Abarelix depot, a GnRH antagonist, v LHRH super-agonists in prostate cancer: differential effects on follicle-stimulating hormone. Abarelix Deport Study group. Mol Urol. 2000;4:275–277.
   PubMedGoogle Scholar
• Huirne JAF, Lambalk CB. Gonadotropin-releasing-hormone receptor antagonists. Lancet. 2001;358(9295):1793–1803.
   PubMed Web of Science ®Google Scholar
• Tombal B, Miller K, Boccon-Gibod L, et al. Additional analysis of the secondary end point of biochemical recurrence rate in a phase 3 trial (CS21) comparing degarelix 80 mg versus leuprolide in prostate cancer patients segmented by baseline characteristics. Eur Urol. 2010;57:836–842.
   PubMed Web of Science ®Google Scholar
• McLeod D, Zinner N, Tomera K, et al. A phase 3, multicenter, open label, randomized study of Abarelix versus leuprolide acetate in men with prostate cancer. Urology. 2001;58:756–761.
   PubMed Web of Science ®Google Scholar
• Broqua P, Riviere PJM, Conn PM, et al. Pharmacological profile of a new, potent, and long-acting gonadotropin-releasing hormone antagonist: degarelix. J Pharm Exp Ther. 2002;301(1):95–102.
   PubMed Web of Science ®Google Scholar
• Boccon-Gibod L, van der Meulen E, Persson BE. An update on the use of gonadotropin-releasing hormone antagonists in prostate cancer. Ther Adv Urol. 2011;3(3):127–140.
   PubMedGoogle Scholar
• Weckermann D, Harzmann R. Hormone therapy in prostate cancer: LHRH antagonists versus LHRH analogues. Eur Urol. 2004;46:279–284.
   PubMed Web of Science ®Google Scholar
• Tornoe CW, Agerso H, Nielsen HA, et al. Population pharmacokinetic modeling of a subcutaneous depot for GnRH antagonist Degarelix. Pharm Res. 2004;21(4):574–584.
   PubMed Web of Science ®Google Scholar
• Klotz L. Pharmacokinetic and pharmacodynamic profile for degarelix for prostate cancer. Expert Opin Drug Metab Toxicol. 2015;11(11):1795–1802.
   PubMed Web of Science ®Google Scholar
• Sonesson A, Rasmussen BB. In vitro and in vivo human metabolism of degarelix, a gonadotropin-releasing hormone receptor blocker. Drug Metab Dispos. 2013;41(7):1339–1346.
   PubMed Web of Science ®Google Scholar
• Suzuki H, Uemura H, Mizokami A, et al. Phase I trial of TAK‐385 in hormone treatment‐naïve Japanese patients with nonmetastatic prostate cancer. Cancer Med. 2019;8:5891–5902.
   PubMed Web of Science ®Google Scholar
• Selvaggi F, Khoe GSS, Van Cangh P, et al. Comparison of abarelix depot (A-D) and goserelin (G) plus bicalutamide (B) in advanced prostate cancer: results of a multicentre, open-label, randomised, phase III study. Eur Urol. 2001;39(Suppl 5):78.
   Google Scholar
• Schröder F, Crawford ED, Axcrona K, et al. Androgen deprivation therapy: past, present and future. BJU Int. 2012;109(Suppl 6):1–12.
   PubMed Web of Science ®Google Scholar
• Soul JW. Utility of LHRH antagonists for advanced prostate cancer. Can J Urol. 2014;21(Suppl 1):22–27.
   PubMed Web of Science ®Google Scholar
• Klotz L, Boccon-Gibod L, Shore ND, et al. 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. 2008;102:1531–1538.
   PubMed Web of Science ®Google Scholar
• Klotz L, Miller K, Crawford ED, et al. Disease control outcomes from analysis of pooled individual patient data from five comparative randomised clinical trials of degarelix versus luteinising hormone releasing hormone agonists. Eur Urol. 2014;66:1101–1108.
   PubMed Web of Science ®Google Scholar
• Sun Y, Xie L, Xu T, et al. Efficacy and safety of degarelix in patients with prostate cancer: results from a phase III study in China. Asian J Urol. 2020 7; Jul(3): 301–308.
   Google Scholar
• Iversen P, Damber JE, Malmberg A, et al. Degarelix monotherapy compared with luteinizing hormone-releasing hormone (LHRH) agonists plus anti-androgen flare protection in advanced prostate cancer: an analysis of two randomized controlled trials. Ther Adv Urol. 2016 Apr;8(2):75–82.
   PubMed Web of Science ®Google Scholar
• Sciarra A, Fasulo A, Ciardi A, et al. A meta-analysis and systematic review of randomized controlled trials with degarelix versus gonadotropin-releasing hormone agonists for advanced prostate cancer. Medicine (Baltimore). 2016 Jul;95(27):e3845.
   PubMed Web of Science ®Google Scholar
• Abufaraj M, Iwata T, Kimura S, et al. Differential impact of gonadotropin-releasing hormone antagonist versus agonist on clinical safety and oncologic outcomes on patients with metastatic prostate cancer: a meta-analysis of randomized controlled trials. Eur Urol. 2021 Jan;79(1):44–53.
   PubMed Web of Science ®Google Scholar
• Anderson J, Al-Ali G, Wirth M, et al. Degarelix versus goserelin (+ antiandrogen flare protection) in the relief of lower urinary tract symptoms secondary to prostate cancer: results from a phase IIIb study (NCT00831233). Urol Int. 2013;90:321–328.
   PubMed Web of Science ®Google Scholar
• Mason M, Richaud P, Bosnyak Z, et al. Degarelix versus goserelin plus bicalutamide in the short-term relief of lower urinary tract symptoms in prostate cancer patients: results of a pooled analysis. Low Urin Tract Symptoms. 2017;9(2):82–88.
   PubMed Web of Science ®Google Scholar
• Mason M, Maldonado Pijoan X, Steidle C, et al. Neoadjuvant androgen deprivation therapy for prostate volume reduction, lower urinary tract symptom relief and quality of life improvement in men with intermediate- to high-risk prostate cancer: a randomised noninferiority trial of degarelix versus goserelin plus bicalutamide. Clin Oncol. 2013;25:190–196.
   PubMed Web of Science ®Google Scholar
• Hata S, Shin T, Abe S, et al. Degarelix as a neoadjuvant hormonal therapy for acute urinary tract toxicity associated with external beam radiotherapy for intermediate- and high-risk prostate cancer: a propensity score matched analysis. Jpn J Clin Oncol. 2021 Mar 3;51(3):478-483.
   Web of Science ®Google Scholar
• Korzeniowski MA, Crook JM, Bowes D, et al. A Phase II trial of 8 weeks of degarelix for prostate volume reduction: efficacy and hormonal recovery. Brachytherapy. 2018 May-Jun;17(3):530–536.
   PubMed Web of Science ®Google Scholar
• Abrahamsson PA, Boccon-Gibod L, Morote J, et al. Factors predicting the off-treatment duration in patients with prostate cancer receiving degarelix as intermittent androgen deprivation therapy. Eur Urol Focus. 2017 Oct;3(4–5):470–479.
   PubMedGoogle Scholar
• Klotz L, Loblaw A, Siemens R, et al. A phase ii, randomized, multicenter study comparing 10 months versus 4 months of degarelix therapy in prolonging the off treatment interval in men with localized prostate cancer receiving intermittent androgen deprivation therapy for biochemical recurrence following radical local therapy. J Urol. 2018 Aug;200(2):335–343.
   PubMed Web of Science ®Google Scholar
• Tosco L, Laenen A, Gevaert T, et al. P.E.A.R.L. (ProstatE cAncer Research Leuven). Neoadjuvant degarelix with or without apalutamide followed by radical prostatectomy for intermediate and high-risk prostate cancer: ARNEO, a randomized, double blind, placebo-controlled trial. BMC Cancer. 2018 Apr 2;18(1):354.
   PubMedGoogle Scholar
• Ozono S, Tsukamoto T, Naito S, et al. Efficacy and safety of a 3-month dosing regimen of degarelix in Japanese patients with prostate cancer: a phase II maintenance-dose-finding study. Jpn J Clin Oncol. 2017 May 1;47(5):438–446.
   PubMed Web of Science ®Google Scholar
• Ozono S, Tsukamoto T, Naito S, et al. Efficacy and safety of 3-month dosing regimen of degarelix in Japanese subjects with prostate cancer: a phase III study. Cancer Sci. 2018 Jun;109(6):1920–1929.
   PubMed Web of Science ®Google Scholar
• Dearnaley D, Saltzstein DR, Sylvester JE, et al. Neo/adjuvant ADT to EBRT: final results of the randomized phase 2 trial of the oral GnRH antagonist, TAK‐385 (relugolix) and degarelix in patients with prostate cancer. Ann Oncol. 2016;27:243‐265.
   Web of Science ®Google Scholar
• Saad F, Bailen JL, Pieczonka CM, et al. Second interim analysis (IA2) results from a phase II trial of TAK‐385, an oral GnRH antagonist, in prostate cancer patients (pts). J Clin Oncol. 2016;34:200.
   Google Scholar
• Dearnaley DP, Saltzstein DR, Sylvester JE, et al. The oral gonadotropin-releasing hormone receptor antagonist relugolix as neoadjuvant/adjuvant androgen deprivation therapy to external beam radiotherapy in patients with localised intermediate-risk prostate cancer: a randomised, open-label, parallel-group phase 2 trial. Eur Urol. 2020 Aug;78(2):184–192.
   PubMed Web of Science ®Google Scholar
• Hupe MC, Hammerer P, Ketz M, et al. Retrospective analysis of patients with prostate cancer initiating gnrh agonists/antagonists therapy using a German claims database: epidemiological and patient outcomes. Front Oncol. 2018 Nov;27(8):543.
   Google Scholar
• Margel D, Peer A, Ber Y, et al. Cardiovascular morbidity in a randomized trial comparing GnRH agonist and GnRH antagonist among patients with advanced prostate cancer and preexisting cardiovascular disease. J Urol. 2019 Dec;202(6):1199–1208.
   PubMed Web of Science ®Google Scholar
• Albertsen PC, Klotz L, Tombal B, et al. Cardiovascular morbidity associated with gonadotropin releasing hormone agonists and an antagonist. Eur Urol. 2014 Mar;65(3):565–573.
   PubMed Web of Science ®Google Scholar
• Ma C, Abeysekera IR, Wenbin X, et al. Comparing the risk of cardiovascular disease following GnRH agonist and GnRH antagonist therapy for patient with prostate cancer: a systematic review and meta-analysis. Minerva Urol Nefrol. 2020 Nov 27. DOI:https://doi.org/10.23736/S0393-2249.20.03756-X. [ Epub ahead of print].
   Google Scholar
• George G, Garmo H, Scailteux LM, et al. Risk of cardiovascular disease following gonadotropin-releasing hormone agonists vs antagonists in prostate cancer: real-world evidence from five databases. Int J Cancer. 2020 Nov 13;148(9):2203–2211. Epub ahead of print.
   PubMed Web of Science ®Google Scholar
• Davey P, Kirby MG. Cardiovascular risk profiles of GnRH agonists and antagonists: real-world analysis from UK general practice. World J Urol. 2020 Sep 26. DOI:https://doi.org/10.1007/s00345-020-03433-3. Epub ahead of print.
   PubMed Web of Science ®Google Scholar
• Olsson H, Petri N, Erichsen L, et al. Effect of Degarelix, a Gonadotropin-releasing hormone receptor antagonist for the treatment of prostate cancer, on cardiac repolarisation in a randomised, placebo and active comparator controlled thorough QT/QTc trial in healthy men. Clin Drug Investig. 2017 Sep;37(9):873–879.
   PubMed Web of Science ®Google Scholar
• Sawazaki H, Araki D, Kitamura Y, et al. Metabolic changes with degarelix vs leuprolide plus bicalutamide in patients with prostate cancer: a randomized clinical study. World J Urol. 2020 Jun;38(6):1465–1471.
   PubMed Web of Science ®Google Scholar
• Tokiwa S, Shimmura H, Nomura S, et al. Degarelix treatment is compatible with diabetes and antithrombotic therapy in patients with prostate cancer. Res Rep Urol. 2017 Dec;6(9):225–232.
   Google Scholar
• Yannucci J, Manola J, Garnick MB, et al. The effect of androgen deprivation therapy on fasting serum lipid and glucose parameters. J Urol. 2006 Aug;176(2):520–525.
   PubMed Web of Science ®Google Scholar
• Mohamad NV, Soelaiman IN, Chin KY. The skeletal effects of gonadotropin-releasing hormone antagonists: a concise review. Endocr Metab Immune Disord Drug Targets. 2020 Dec 16;21. https://doi.org/10.2174/1871530321666201216164410. Epub ahead of print.
   Google Scholar
• Jayusman PA, Mohamed IN, Shuid AN. The effects of chemical castration with degarelix on bone turnover: densitometric and biomechanics bone properties of male rats. Int J Endocrinol Metab. 2018 Jul 2;16(3):e64038.
   PubMed Web of Science ®Google Scholar
• Clinton TN, Woldu SL, Raj GV. Degarelix versus luteinizing hormone-releasing hormone agonists for the treatment of prostate cancer. Expert Opin Pharmacother. 2017;18(8):825–832.
   PubMed Web of Science ®Google Scholar
• Atchia KS, Wallis CJD, Fleshner N, et al. Switching from a gonadotropin-releasing hormone (GnRH) agonist to a GnRH antagonist in prostate cancer patients: a systematic review and meta-analysis. Can Urol Assoc J. 2020 Feb;14(2):36–41.
   PubMed Web of Science ®Google Scholar
• Cucchiara V, Yang JC, Liu C, et al. GnRH antagonists have direct inhibitory effects on castration-resistant prostate cancer via intracrine androgen and AR-V7 expression. Mol Cancer Ther. 2019;18(10):1811–1821.
   PubMed Web of Science ®Google Scholar
• Belkacemi Y, Latorzeff I, Hasbini A, et al. Patterns of practice of androgen deprivation therapy combined to radiotherapy in favorable and unfavorable intermediate risk prostate cancer. Results of the PROACT survey from the French GETUG radiation oncology group. Cancer Radiother. 2020 Dec;24(8):892–897.
   PubMed Web of Science ®Google Scholar
• Crawford ED, Schally AV. The role of FSH and LH in prostate cancer and cardiometabolic comorbidities. Can J Urol. 2020 Apr;27(2):10167–10173.
   PubMedGoogle Scholar
• ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2017 Jun 17. Identifier NCT02663908, A trial comparing cardiovascular safety of degarelix versus leuprolide in patients with advanced prostate cancer and cardiovascular disease (PRONOUNCE); 2016 Jan 22 [cited 2017 Sep 5]; Available from: https://clinicaltrials.gov/ct2/show/NCT02663908.
   Google Scholar