215
Views
5
CrossRef citations to date
0
Altmetric
Review

Progress in Clinical Research on Gonadotropin-Releasing Hormone Receptor Antagonists for the Treatment of Prostate Cancer

, , , , , , & show all
Pages 639-649 | Published online: 16 Feb 2021

References

  • CenterMM, JemalA, Lortet-TieulentJ, et al. International variation in prostate cancer incidence and mortality rates. Eur Urol. 2012;61(6):1079–1092. doi:10.1016/j.eururo.2012.02.05422424666
  • CulpMB, SoerjomataramI, EfstathiouJA, BrayF, JemalA. Recent global patterns in prostate cancer incidence and mortality rates. Eur Urol. 2020;77(1):38–52. doi:10.1016/j.eururo.2019.08.00531493960
  • HugginsC, HodgesCV. Studies on prostatic cancer. I. The effect of castration, of estrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate. 1941. J Urol. 2002;167(2 Pt 2):948–951. doi:10.1016/S0022-5347(02)80307-X11905923
  • RickFG, BlockNL, SchallyAV. Agonists of luteinizing hormone-releasing hormone in prostate cancer. Expert Opin Pharmacother. 2013;14(16):2237–2247. doi:10.1517/14656566.2013.83432823984804
  • SchallyAV, ArimuraA, BabaY, et al. Isolation and properties of the FSH and LH-releasing hormone. Biochem Biophys Res Commun. 1971;43(2):393–399. doi:10.1016/0006-291X(71)90766-24930860
  • SchallyAV, ArimuraA, KastinAJ, et al. Gonadotropin-releasing hormone: one polypeptide regulates secretion of luteinizing and follicle-stimulating hormones. Science. 1971;173(4001):1036–1038. doi:10.1126/science.173.4001.10364938639
  • RickFG, SchallyAV. Bench-to-bedside development of agonists and antagonists of luteinizing hormone-releasing hormone for treatment of advanced prostate cancer. Urol Oncol. 2015;33(6):270–274. doi:10.1016/j.urolonc.2014.11.00625512159
  • KlotzL, Boccon-GibodL, ShoreND, 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(11):1531–1538. doi:10.1111/j.1464-410X.2008.08183.x19035858
  • TsushimaT, NasuY, SaikaT, et al. Optimal starting time for flutamide to prevent disease flare in prostate cancer patients treated with a gonadotropin-releasing hormone agonist. Urol Int. 2001;66(3):135–139. doi:10.1159/00005659211316974
  • SchallyAV. Luteinizing hormone-releasing hormone analogs: their impact on the control of tumorigenesis. Peptides. 1999;20(10):1247–1262. doi:10.1016/S0196-9781(99)00130-810573298
  • BajuszS, KovacsM, GazdagM, et al. Highly potent antagonists of luteinizing hormone-releasing hormone free of edematogenic effects. Proc Natl Acad Sci U S A. 1988;85(5):1637–1641. doi:10.1073/pnas.85.5.16373278323
  • Gonzalez-BarcenaD, Vadillo-BuenfilM, Cortez-MoralesA, et al. Luteinizing hormone-releasing hormone antagonist cetrorelix as primary single therapy in patients with advanced prostatic cancer and paraplegia due to metastatic invasion of spinal cord. Urology. 1995;45(2):275–281. doi:10.1016/0090-4295(95)80018-27531902
  • Gonzalez-BarcenaD, Vadillo-BuenfilM, Gomez-OrtaF, et al. Responses to the antagonistic analog of LH-RH (SB-75, Cetrorelix) in patients with benign prostatic hyperplasia and prostatic cancer. Prostate. 1994;24(2):84–92. doi:10.1002/pros.29902402067508623
  • ShoreND, AbrahamssonPA, AndersonJ, CrawfordED, LangeP. New considerations for ADT in advanced prostate cancer and the emerging role of GnRH antagonists. Prostate Cancer Prostatic Dis. 2013;16(1):7–15. doi:10.1038/pcan.2012.2522751146
  • ShoreND, SaadF, CooksonMS, et al. Oral relugolix for androgen-deprivation therapy in advanced prostate cancer. N Engl J Med. 2020;382(23):2187–2196. doi:10.1056/NEJMoa200432532469183
  • Van PoppelH, TombalB, de la RosetteJJ, PerssonBE, JensenJK, Kold OlesenT. 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. 2008;54(4):805–813. doi:10.1016/j.eururo.2008.04.06518538469
  • GittelmanM, PommervillePJ, PerssonBE, JensenJK, OlesenTK. A 1-year, open label, randomized phase II dose finding study of degarelix for the treatment of prostate cancer in North America. J Urol. 2008;180(5):1986–1992. doi:10.1016/j.juro.2008.07.03318801505
  • OzonoS, UedaT, HoshiS, et al. 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. 2012;42(6):477–484. doi:10.1093/jjco/hys03522457321
  • OzonoS, TsukamotoT, NaitoS, 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;47(5):438–446. doi:10.1093/jjco/hyx01128334771
  • OzonoS, TsukamotoT, NaitoS, 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;109(6):1920–1929. doi:10.1111/cas.1360029624800
  • Tombal B, Tammela TLJ, Wolff JM, et al. P109 Efficacy and safety of a 3-monthly depot of degarelix compared with goserelin in prostate cancer. Eur Urol Suppl. 2012;11(5):228–229. doi:10.1016/S1569-9056(13)60476-5
  • MiyazawaY, SekineY, SyutoT, et al. A gonadotropin-releasing hormone antagonist reduces serum adrenal androgen levels in prostate cancer patients. BMC Urol. 2017;17(1):70. doi:10.1186/s12894-017-0261-z28851333
  • TombalB, MillerK, Boccon-GibodL, 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(5):836–842. doi:10.1016/j.eururo.2009.11.02919962227
  • SchroderFH, TombalB, MillerK, et al. Changes in alkaline phosphatase levels in patients with prostate cancer receiving degarelix or leuprolide: results from a 12-month, comparative, phase III study. BJU Int. 2010;106(2):182–187. doi:10.1111/j.1464-410X.2009.08981.x19912212
  • HussainM, GoldmanB, TangenC, et al. Prostate-specific antigen progression predicts overall survival in patients with metastatic prostate cancer: data from southwest oncology group trials 9346 (intergroup study 0162) and 9916. J Clin Oncol. 2009;27(15):2450–2456. doi:10.1200/JCO.2008.19.981019380444
  • HussainM, TangenCM, HiganoC, et al. Absolute prostate-specific antigen value after androgen deprivation is a strong independent predictor of survival in new metastatic prostate cancer: data from southwest oncology group trial 9346 (INT-0162). J Clin Oncol. 2006;24(24):3984–3990. doi:10.1200/JCO.2006.06.424616921051
  • CrawfordED, ShoreND, MoulJW, 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):1122–1128. doi:10.1016/j.urology.2014.01.01324661333
  • CrawfordED, TombalB, MillerK, 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(3):889–897. doi:10.1016/j.juro.2011.04.08321788033
  • IversenP, DamberJE, MalmbergA, PerssonBE, KlotzL. 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;8(2):75–82. doi:10.1177/175628721562147127034720
  • RaduPDA, PichonPDC, CamparoMDP, AntoineMDM. Expression of follicle-stimulating hormone receptor in tumor blood vessels. N Engl J Med. 2010;363:1621–1630. doi:10.1056/NEJMoa100128320961245
  • Ben-JosefE, YangSY, JiTH, et al. Hormone-refractory prostate cancer cells express functional follicle-stimulating hormone receptor (FSHR). J Urol. 1999;161(3):970–976. doi:10.1016/S0022-5347(01)61831-710022736
  • CrawfordED, TombalB, KeaneT, et al. FSH suppression and tumour control in patients with prostate cancer during androgen deprivation with a GnRH agonist or antagonist. Scand J Urol. 2018;52(5–6):349–357. doi:10.1080/21681805.2018.152237230624128
  • HoareD, SkinnerTA, BlackA, Robert SiemensD. Serum follicle-stimulating hormone levels predict time to development of castration-resistant prostate cancer. Can Urol Assoc J. 2015;9(3–4):122–127. doi:10.5489/cuaj.254526085869
  • SunY, XieL, XuT, et al. Efficacy and safety of degarelix in patients with prostate cancer: results from a phase III study in China. Asian J Urol. 2019.
  • YouD, ChungBH, LeeSE, KimCS. Efficacy and safety of degarelix in Korean patients with prostate cancer requiring androgen deprivation therapy: open-label multicenter phase III study. Prostate Int. 2015;3(1):22–26. doi:10.1016/j.prnil.2015.02.00526157762
  • KlotzL, MillerK, CrawfordED, 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(6):1101–1108. doi:10.1016/j.eururo.2013.12.06324440304
  • AbufarajM, IwataT, KimuraS, 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. 2020.
  • AxcronaK, AaltomaaS, da SilvaCM, et al. Androgen deprivation therapy for volume reduction, lower urinary tract symptom relief and quality of life improvement in patients with prostate cancer: degarelix vs goserelin plus bicalutamide. BJU Int. 2012;110(11):1721–1728. doi:10.1111/j.1464-410X.2012.11107.x22500884
  • AndersonJ, Al-AliG, WirthM, 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(3):321–328. doi:10.1159/00034542323258223
  • MasonM, Maldonado PijoanX, SteidleC, 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 non-inferiority trial of degarelix versus goserelin plus bicalutamide. Clin Oncol (R Coll Radiol). 2013;25(3):190–196. doi:10.1016/j.clon.2012.09.01023257248
  • MasonM, RichaudP, BosnyakZ, MalmbergA, NeijberA. 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. doi:10.1111/luts.1211428394498
  • SakaiM, ElhilaliM, PapadopoulosV. The GnRH antagonist degarelix directly inhibits benign prostate hyperplasia cell growth. Horm Metab Res. 2015;47(12):925–931. doi:10.1055/s-0035-155589926197852
  • Boccon-GibodL, AlbersP, MoroteJ, et al. Degarelix as an intermittent androgen deprivation therapy for one or more treatment cycles in patients with prostate cancer. Eur Urol. 2014;66(4):655–663. doi:10.1016/j.eururo.2014.05.03724954791
  • KlotzL, LoblawA, SiemensR, 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;200(2):335–343. doi:10.1016/j.juro.2018.03.01029534997
  • InoueT, MizowakiT, KabataD, et al. Recovery of serum testosterone levels and sexual function in patients treated with short-term luteinizing hormone-releasing hormone antagonist as a neoadjuvant therapy before external radiotherapy for intermediate-risk prostate cancer: preliminary prospective study. Clin Genitourin Cancer. 2018;16(2):135–141.e131. doi:10.1016/j.clgc.2017.09.00929051056
  • HagiwaraK, KoieT, OhyamaC, et al. Efficacy of a neoadjuvant gonadotropin-releasing hormone antagonist plus low-dose estramustine phosphate in high-risk prostate cancer: a single-center study. Int Urol Nephrol. 2017;49(5):811–816. doi:10.1007/s11255-017-1546-628213801
  • SayyidRK, EvansA, HerseyK, et al. A phase II, randomized, open-label study of neoadjuvant degarelix versus lhrh agonist in prostate cancer patients prior to radical prostatectomy. Clin Cancer Res. 2017;23(8):1974–1980. doi:10.1158/1078-0432.CCR-16-179027756786
  • MillerK, SimsonG, GobleS, PerssonBE. Efficacy of degarelix in prostate cancer patients following failure on luteinizing hormone-releasing hormone agonist treatment: results from an open-label, multicentre, uncontrolled, phase II trial (CS27). Ther Adv Urol. 2015;7(3):105–115. doi:10.1177/175628721557447926161141
  • EzakiT, KosakaT, MizunoR, et al. Efficacy of treatment with a GnRH antagonist in prostate cancer patients previously treated with a GnRH agonist. Cancer Chemother Pharmacol. 2015;76(2):301–306. doi:10.1007/s00280-015-2798-426055219
  • Masson-LecomteA, GuyL, PedronP, et al. A switch from GnRH agonist to GnRH antagonist in castration-resistant prostate cancer patients leads to a low response rate on PSA. World J Urol. 2013;31(2):339–343. doi:10.1007/s00345-012-0841-122527669
  • IversenP, KarupC, van der MeulenE, TankoLB, HuhtaniemiI. Hot flushes in prostatic cancer patients during androgen-deprivation therapy with monthly dose of degarelix or leuprolide. Prostate Cancer Prostatic Dis. 2011;14(2):184–190. doi:10.1038/pcan.2011.1121445092
  • AlbertsenPC, KlotzL, TombalB, GradyJ, OlesenTK, NilssonJ. Cardiovascular morbidity associated with gonadotropin releasing hormone agonists and an antagonist. Eur Urol. 2014;65(3):565–573. doi:10.1016/j.eururo.2013.10.03224210090
  • DaveyP, KirbyMG. Cardiovascular risk profiles of GnRH agonists and antagonists: real-world analysis from UK general practice. World J Urol. 2020. doi:10.1007/s00345-020-03433-3
  • MargelD, PeerA, BerY, 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;202(6):1199–1208. doi:10.1097/JU.000000000000038431188734
  • CardwellCR, O’SullivanJM, JainS, et al. The risk of cardiovascular disease in prostate cancer patients receiving androgen deprivation therapies. Epidemiology. 2020;31(3):432–440. doi:10.1097/EDE.000000000000113231651660
  • LeeD, NielsenSK, van KeepM, AnderssonF, GreeneD. Quality of life improvement in patients treated with degarelix versus leuprorelin for advanced prostate cancer. J Urol. 2015;193(3):839–846. doi:10.1016/j.juro.2014.09.09825264336
  • MacLeanDB, ShiH, FaesselHM, SaadF. Medical castration using the investigational oral GnRH antagonist TAK-385 (relugolix): phase 1 study in healthy males. J Clin Endocrinol Metab. 2015;100(12):4579–4587. doi:10.1210/jc.2015-277026502357
  • SuzukiH, UemuraH, MizokamiA, et al. Phase I trial of TAK-385 in hormone treatment-naive Japanese patients with nonmetastatic prostate cancer. Cancer Med. 2019;8(13):5891–5902. doi:10.1002/cam4.244231429205
  • SaadF, BailenJL, PieczonkaCM, 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(2):200. doi:10.1200/jco.2016.34.2_suppl.200
  • DearnaleyDP, SaltzsteinDR, SylvesterJE, 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;78(2):184–192. doi:10.1016/j.eururo.2020.03.00132273183