Will GnRH antagonists improve prostate cancer treatment?

Trends in Endocrinology and Metabolism

Volumn 20, Issue 1, 2009, Pages 43-50

  Huhtaniemi, Ilpo ^a   White, Richard ^b   McArdle, Craig A ^c   Persson, Bo Eric ^b,d  

^a IMPERIAL COLLEGE LONDON   (United Kingdom)

^b Ferring Pharmaceuticals AS   (Denmark)

^c UNIVERSITY OF BRISTOL   (United Kingdom)

^d Elisabethsjukhuset   (Sweden)

Author keywords

[No Author keywords available]

Indexed keywords

ABARELIX; ACYCLINE; BICALUTAMIDE; CETRORELIX; DEGARELIX; FOLLITROPIN; GANIRELIX; GONADORELIN; GONADORELIN AGONIST; GONADORELIN ANTAGONIST; GONADOTROPIN; HISTRELIN; ITURELIX; LEUPRORELIN; MER 104; NBI 42902; TESTOSTERONE; TEVERELIX; TRIPTORELIN; UNCLASSIFIED DRUG;

AMINO ACID SEQUENCE; ANAPHYLAXIS; CANCER CHEMOTHERAPY; CLINICAL TRIAL; DRUG DELIVERY SYSTEM; DRUG EFFICACY; DRUG HYPERSENSITIVITY; DRUG MARKETING; DRUG SAFETY; DRUG TOLERABILITY; EDEMA; HISTAMINE RELEASE; HORMONAL REGULATION; HOT FLUSH; HUMAN; NONHUMAN; PRIORITY JOURNAL; PROSTATE CANCER; RECEPTOR BLOCKING; REVIEW; SINGLE DRUG DOSE; TREATMENT FAILURE; TREATMENT RESPONSE;

ANIMALS; ANTINEOPLASTIC AGENTS, HORMONAL; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; DRUG DESIGN; GONADOTROPIN-RELEASING HORMONE; HORMONE ANTAGONISTS; HUMANS; MALE; MODELS, BIOLOGICAL; OLIGOPEPTIDES; PROSTATIC NEOPLASMS; TREATMENT OUTCOME;

EID: 58149144740     PISSN: 10432760     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.tem.2008.09.003     Document Type: Review

References (81)

1. Conn P.M., and Crowley Jr. W.F. Gonadotropin-releasing hormone and its analogs. Annu. Rev. Med. 45 (1994) 391-405
2. Sealfon S.C., et al. Molecular mechanisms of ligand interaction with the gonadotropin-releasing hormone receptor. Endocr. Rev. 18 (1997) 180-205
3. Belchetz P.E., et al. Hypophysial responses to continuous and intermittent delivery of hypopthalamic gonadotropin-releasing hormone. Science 202 (1978) 631-633
4. Chengalvala M.V., et al. GnRH agonists and antagonists in cancer therapy. Curr. Med. Chem. Anticancer Agents. 3 (2003) 399-410
5. Betz S.F., et al. Non-peptide gonadotropin-releasing hormone receptor antagonists. J. Med. Chem. 51 (2008) 3331-3348
6. Reiter E., and Lefkowitz R.J. GRKs and β-arrestins: roles in receptor silencing, trafficking and signaling. Trends Endocrinol. Metab. 17 (2006) 159-165
7. Shenoy S.K., and Lefkowitz R.J. Multifaceted roles of β-arrestins in the regulation of seven-membrane-spanning receptor trafficking and signalling. Biochem. J. 375 (2003) 503-515
8. Conn P.M., et al. Mechanism of action of gonadotropin releasing hormone. Annu. Rev. Physiol. 48 (1986) 495-513
9. Millar R.P., et al. Gonadotropin-releasing hormone receptors. Endocr. Rev. 25 (2004) 235-275
10. Reinhart J., et al. Molecular cloning and expression of cDNA encoding the murine gonadotropin-releasing hormone receptor. J. Biol. Chem. 267 (1992) 21281-21284
11. Tsutsumi M., et al. Cloning and functional expression of a mouse gonadotropin-releasing hormone receptor. Mol. Endocrinol. 6 (1992) 1163-1169
12. Davidson J.S., et al. Absence of rapid desensitization of the mouse gonadotropin-releasing hormone receptor. Biochem. J. 300 (1994) 299-302
13. McArdle C.A., et al. Signalling, cycling and desensitisation of gonadotropin-releasing hormone receptors. J. Endocrinol. 173 (2002) 1-11
14. 2+ mobilization. J. Biol. Chem. 271 (1996) 23711-23717
15. Willars G.B., et al. Acute desensitization of phospholipase C-coupled muscarinic M3 receptors but not gonadotropin-releasing hormone receptors co-expressed in αT3-1 cells: implications for mechanisms of rapid desensitization. Biochem. J. 333 (1998) 301-308
16. 2+ responses in αT3-1 gonadotropes. J. Biol. Chem. 276 (2001) 3123-3129
17. Anderson L., et al. Rapid desensitization of GnRH-stimulated intracellular signalling events in αT3-1 and HEK-293 cells expressing the GnRH receptor. Endocrinology 136 (1995) 5228-5231
18. Liu F., et al. Gonadotropin-releasing hormone-desensitized LßT2 gonadotrope cells are refractory to acute protein kinase C, cyclic AMP, and calcium-dependent signaling. Endocrinology 144 (2003) 4354-4365
19. Herbst K.L. Gonadotropin-releasing hormone antagonists. Curr. Opin. Pharmacol. 3 (2003) 660-666
20. Kovacs M., et al. Luteinizing hormone-releasing hormone (LH-RH) antagonist Cetrorelix down-regulates the mRNA expression of pituitary receptors for LH-RH by counteracting the stimulatory effect of endogenous LH-RH. Proc. Natl. Acad. Sci. U. S. A. 98 (2001) 1829-1834
21. Broqua P., et al. Pharmacological profile of a new, potent, and long-acting gonadotropin-releasing hormone antagonist: degarelix. J. Pharmacol. Exp. Ther. 301 (2002) 95-102
22. Huhtaniemi I., et al. Pituitary-testicular function of prostatic cancer patients during treatment with a gonadotropin-releasing hormone agonist analog. II. Endocrinology and histology of the testis. J. Androl. 8 (1987) 363-373
23. Burger L.L., et al. Regulation of gonadotropin subunit gene transcription. J. Mol. Endocrinol. 33 (2004) 559-584
24. Bedecarrats G.Y., and Kaiser U.B. Differential regulation of gonadotropin subunit gene promoter activity by pulsatile gonadotropin-releasing hormone (GnRH) in perifused L beta T2 cells: role of GnRH receptor concentration. Endocrinology 144 (2003) 1802-1811
25. Haisenleder D.J., et al. Gonadotropin-releasing hormone pulses are required to maintain activation of mitogen-activated protein kinase: role in stimulation of gonadotrope gene expression. Endocrinology 139 (1998) 3104-3111
26. Horvath J.E. Effects of long-term treatment with the luteinizing hormone-releasing hormone (LHRH) agonist Decapeptyl and the LHRH antagonist cetrorelix on the levels of pituitary LHRH receptors and their mRNA expression in rats. Proc. Natl. Acad. Sci. U. S. A. 99 (2002) 15048-15053
27. Yasin M., et al. Gonadotropin-releasing hormone (GnRH) pulse pattern regulates GnRH receptor gene expression: augmentation by estradiol. Endocrinology 136 (1995) 1559-1564
28. Princivalle M., et al. Rapid suppression of plasma testosterone levels and tumor growth in the dunning rat model treated with degarelix, a new gonadotropin-releasing hormone antagonist. J. Pharmacol. Exp. Ther. 320 (2007) 1113-1118
29. Jungwirth A., et al. Luteinizing hormone-releasing hormone antagonist cetrorelix (SB-75) and bombesin antagonist RC-3940-II inhibit the growth of androgen-independent PC-3 prostate cancer in nude mice. Prostate 32 (1997) 164-172
30. Jungwirth A., et al. Inhibition of growth of androgen-independent DU-145 prostate cancer in vivo by luteinising hormone-releasing hormone antagonist cetrorelix and bombesin antagonists RC-3940-II and RC-3950-II. Eur. J. Cancer 33 (1997) 1141-1148
31. Marelli M.M., et al. Luteinizing hormone-releasing hormone agonists interfere with the mitogenic activity of the insulin-like growth factor system in androgen-independent prostate cancer cells. Endocrinology 140 (1999) 329-334
32. Wells A., et al. Luteinizing hormone-releasing hormone agonist limits DU-145 prostate cancer growth by attenuating epidermal growth factor receptor signaling. Clin. Cancer Res. 8 (2002) 1251-1257
33. McLeod D., et al. A phase 3, multicenter, open-label, randomized study of abarelix versus leuprolide acetate in men with prostate cancer. Urology 58 (2001) 756-761
34. Huhtaniemi I., et al. Treatment of prostatic cancer with a gonadotropin-releasing hormone agonist analog: acute and long term effects on endocrine functions of testis tissue. J. Clin. Endocrinol. Metab. 61 (1985) 698-704
35. Labrie F., et al. Gonadotropin-releasing hormone agonists in the treatment of prostate cancer. Endocr. Rev. 26 (2005) 361-379
36. Zinner N.R., et al. Similar frequency of testosterone surge after repeat injections of goserelin (Zoladex) 3.6 mg and 10.8 mg: results of a randomized open-label trial. Urology 64 (2004) 1177-1181
37. Morote J., et al. Redefining clinically significant castration levels in patients with prostate cancer receiving continuous androgen deprivation therapy. J. Urol. 178 (2007) 1290-1295
38. Huhtaniemi I.T., et al. Serum bioactive and immunoreactive follicle-stimulating hormone in prostatic cancer patients during gonadotropin-releasing hormone agonist treatment and after orchidectomy. J. Clin. Endocrinol. Metab. 66 (1988) 308-313
39. Garnick M.B., and Campion M. Abarelix Depot, a GnRH antagonist, v LHRH superagonists in prostate cancer: differential effects on follicle-stimulating hormone. Abarelix Depot study group. Mol. Urol. 4 (2000) 275-277
40. Reissmann T., et al. The LHRH antagonist cetrorelix: a review. Hum. Reprod. Update 6 (2000) 322-331
41. Adamopoulos D.A., et al. Testicular secretion after pulsatile human menopausal gonadotropin therapy in gonadotropin-releasing hormone agonist desensitized dysspermic men. Fertil. Steril. 62 (1994) 155-161
42. Foresta C., et al. Suppression of the high endogenous levels of plasma FSH in infertile men are associated with improved Sertoli cell function as reflected by elevated levels of plasma inhibin B. Hum. Reprod. 19 (2004) 1431-1437
43. Porter A., et al. Advancing perspectives on prostate cancer: multihormonal influences in pathogenesis. Mol. Urol. 5 (2001) 181-188
44. Sun L., et al. FSH directly regulates bone mass. Cell 125 (2006) 247-260
45. Beer T.M., et al. Targeting FSH in androgen-independent prostate cancer: abarelix for prostate cancer progressing after orchiectomy. Urology 63 (2004) 342-347
46. Huhtaniemi I., et al. Response of circulating gonadotropin levels to GnRH agonist treatment in prostatic cancer. J. Androl. 12 (1991) 46-53
47. Jaakkola T., et al. The ratios of serum bioactive/immunoreactive luteinizing hormone and follicle-stimulating hormone in various clinical conditions with increased and decreased gonadotropin secretion: reevaluation by a highly sensitive immunometric assay. J. Clin. Endocrinol. Metab. 70 (1990) 1496-1505
48. Tomera K., et al. The gonadotropin-releasing hormone antagonist abarelix depot versus luteinizing hormone releasing hormone agonists leuprolide or goserelin: initial results of endocrinological and biochemical efficacies in patients with prostate cancer. J. Urol. 165 (2001) 1585-1589
49. Koch M., et al. An open-label study of abarelix in men with symptomatic prostate cancer at risk of treatment with LHRH agonists. Urology 62 (2003) 877-882
50. Van Poppel H., and Nilsson S. Testosterone surge: rationale for gonadotropin-releasing hormone blockers?. Urology 71 (2008) 1001-1006
51. Trachtenberg J., et al. A phase 3, multicenter, open label, randomized study of abarelix versus leuprolide plus daily antiandrogen in men with prostate cancer. J. Urol. 167 (2002) 1670-1674
52. Sundaram K., et al. Antagonists of luteinizing hormone releasing hormone bind to rat mast cells and induce histamine release. Agents Actions 25 (1988) 307-313
53. Rivier J.E., et al. New effective gonadotropin releasing hormone antagonists with minimal potency for histamine release in vitro. J. Med. Chem. 29 (1986) 1846-1851
54. Jiang G., et al. GnRH antagonists: a new generation of long acting analogues incorporating p-ureido-phenylalanines at positions 5 and 6. J. Med. Chem. 44 (2001) 453-467
55. Seidenfeld J., et al. Single-therapy androgen suppression in men with advanced prostate cancer: a systematic review and meta-analysis. Ann. Intern. Med. 132 (2000) 566-577
56. Kinouchi T., et al. Failure to maintain the suppressed level of serum testosterone during luteinizing hormone-releasing hormone agonist therapy in a patient with prostate cancer. Int. J. Urol. 9 (2002) 359-361
57. Krongrad A., et al. Resistance to gonadotropin-releasing hormone agonist in a patient with metastatic prostate cancer. South. Med. J. 90 (1997) 460-461
58. Oefelein M.G., and Cornum R. Failure to achieve castrate levels of testosterone during luteinizing hormone releasing hormone agonist therapy: the case for monitoring serum testosterone and a treatment decision algorithm. J. Urol. 164 (2000) 726-729
59. Rocco B., et al. Gn-RH antagonist possible response, after Gn-RH agonist failure in a man with metastatic prostate cancer. Anticancer Res. 25 (2005) 577-578
60. Smith M.R., and McGovern F.J. Gonadotropin-releasing hormone agonist failure in a man with prostate cancer. J. Urol. 166 (2001) 211
61. Iversen P., et al. LHRH analogue as a depot preparation (Zoladex) in the treatment of advanced carcinoma of the prostate followed by orchiectomy as a second line therapy - a phase II study. Scand. J. Urol. Nephrol. 23 (1989) 177-183
62. Curry III E.A., and Sweeney C.J. Resistance to luteinizing hormone releasing hormone agonist therapy for metastatic prostate cancer. J. Urol. 168 (2002) 193
63. Daskivich T.J., and Oh W.K. Failure of gonadotropin-releasing hormone agonists with and without sterile abscess formation at depot sites: insight into mechanisms?. Urology 67 (2006) 1084 e15-7
64. Ogan K., et al. Gonadotropin releasing hormone analogue antiandrogen failure secondary to a pituitary adenoma. J. Urol. 160 (1998) 497-498
65. Smith M.R. Obesity and sex steroids during gonadotropin-releasing hormone agonist treatment for prostate cancer. Clin. Cancer Res. 13 (2007) 241-245
66. Gittelman, M. et al. A one-year, open-label, randomized phase II dose-finding study of degarelix, a novel gonadotropin-releasing hormone (GnRH) blocker, in the treatment of prostate cancer in North America. J. Urol. (in press)
67. Van Poppel H., et al. 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 (2008) 805-815
68. Boccon-Gibod L., et al. Degarelix compared to leuprolide depot 7.5 mg in a 12-month randomized, open-label, parallel-group phase III study in prostate cancer patients. Eur. Urol. Suppl. 7 (2008) 205
69. Gonzalez-Barcena D., 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 45 (1995) 275-281
70. Gonzalez-Barcena D., et al. Responses to the antagonistic analog of LH-RH (SB-75, Cetrorelix) in patients with benign prostatic hyperplasia and prostatic cancer. Prostate 24 (1994) 84-92
71. PHRMA report. (2008) Medicines in development for cancer. Available at: http://www.phrma.org/files/meds_in_dev/cancer2008.pdf.
72. Merrion Pharmaceuticals Annual Report 2007. Available at: http://files.shareholder.com/downloads/MERR/405389531x0x205071/138f9ece-d904-470e-abe2-237fde20226a/205071.pdf.
73. Herbst K.L., et al. Acyline: the first study in humans of potent, new gonadotropin-releasing hormone antagonist. J. Clin. Endocrinol. Metab. 87 (2002) 3215-3220
74. Maclean C., et al. Efficacy and safety of teverelix LA, a new GnRH antagonist in patients with advanced prostate cancer. Results from a phase II multi-centre, open-label, pilot study. Eur. Urol. Suppl. 6 (2006) 87
75. Debruyne F.M. Gonadotropin-releasing hormone in the management of prostate cancer. Rev. Urol. 6 Suppl 7 (2004) S25-S32
76. Cook T., and Sheridan W.P. Development of GnRH antagonists for prostate cancer: new approaches to treatment. Oncologist 5 (2000) 162-168
77. Schmidt F., et al. [Ac-D-NAL(2)1,4FD-Phe2,D-Trp3,D-Arg6]-LHRH, a potent antagonist of LHRH, produces transient edema and behavioral changes in rats. Contraception 29 (1984) 283-289
78. Cox M.C., et al. Leuprolide acetate given by a subcutaneous extended-release injection: less of a pain?. Expert Rev. Anticancer Ther. 5 (2005) 605-611
79. ® 6: achieving optimal testosterone control with the convenience of a twice-a-year formulation. Eur. Urol. Suppl. 6 (2007) 840-845
80. Schlegel P.N. Efficacy and safety of histrelin subdermal implant in patients with advanced prostate cancer. J. Urol. 175 (2006) 1353-1358
81. Tornoe C.W., et al. Population pharmacokinetic/pharmacodynamic (PK/PD) modelling of the hypothalamic-pituitary-gonadal axis following treatment with GnRH analogues. Br. J. Clin. Pharmacol. 63 (2007) 648-664