PL EN


Preferences help
enabled [disable] Abstract
Number of results
Journal
2019 | 9 | 4 | 73-87
Article title

Triptorelin in androgen depravation therapy of advanced prostate cancer

Content
Title variants
Languages of publication
EN
Abstracts
EN
Triptorelin as the luteinizing hormone releasing hormone (LHRH) analogue has its own place among other available forms of androgen-depravation therapy (ADT) of locally advanced and metastatic prostate cancer (PCa). Nowadays, in times of development of new therapies in castration-resistant PCa, ADT remains the back bone therapy, which may be supplemented with one of novel drugs. The results of basic research indicate, that apart from the main mechanism of action based on lowering a testosterone concentration to the castration level, triptorelin may have a direct inhibitory effect on tumor cells. Formulations of tryptorelin are available to administer as 1-month, 3-months and 6-months sustained-release forms that may be given intramuscularly or subcutaneously. Constant concentration of triptoreline is maintained by using special microspheres in drug production. Pharmacokinetic and pharmacodynamic properties of particular forms were extensively tested, which allows for safe usage and retain of predictable and high efficacy. Indicators of effective ADT are fast reduction and maintenance of the state of castration. This phenomenon translates into a decrease of the prostate-specific antigen and longer survival. Triptorelin successfully meets these objectives based on a number of phase I–III studies. There is a noticeable lack of comparative studies on effectiveness of particular ADT forms. This may stem from an assumption, that all LHRH analogues demonstrate similar effectiveness because of the class effect. However, some evidence highlight significant differences in efficacy among these drugs. Triptorelin compares especially favourably, particularly as a drug reducing the testosterone level to the lower recommended values (< 20 ng/dl). Side effect profile during the therapy with triptorelin is largely the result of inhibition of the hypothalamic pituitary-testicular axis. Hormonal disturbances linked to hipoandrogenism cause changes in lipid metabolism and glucose tolerance, which may influence the cardiovascular risk. This article is a review of key reports regarding triptorelin and a summary of the role that triptorelin plays in contemporary ADT in advanced PCa.
Discipline
Publisher

Journal
Year
Volume
9
Issue
4
Pages
73-87
Physical description
Contributors
  • Urology Clinic of Medical Postgraduate Education Center, Department of Urology, Independent Public Hospital them. prof. Witold Orlowski, Medical Postgraduate Education Centre, mieszkokozikowski9@gmail.com
author
  • Urology Clinic of Medical Postgraduate Education Center, Department of Urology, Independent Public Hospital them. prof. Witold Orlowski, Medical Postgraduate Education Centre
References
  • 1. Bray F, Ferlay J, Soerjomataram I et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018; 68(6): 394-424.
  • 2. Potosky AL. The role of increasing detection in the rising incidence of prostate cancer. JAMA 1995; 273(7): 548-52.
  • 3. Ilic D, Neuberger MM, Djulbegovic M et al. Screening for prostate cancer. Cochrane database Syst Rev 2013; Issue 1. Art. No.: CD004720.
  • 4. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin 2019; 69(1): 7-34.
  • 5. Dall’Era MA, deVere-White R, Rodriguez D et al. Changing Incidence of Metastatic Prostate Cancer by Race and Age, 1988–2015. Eur Urol Focus 2018.
  • 6. Green SM, Mostaghel EA, Nelson PS. Androgen action and metabolism in prostate cancer. Mol Cell Endocrinol 2012; 360(1-2): 3-13.
  • 7. Pagliarulo V, Bracarda S, Eisenberger MA et al. Contemporary role of androgen deprivation therapy for prostate cancer. Eur Urol 2012; 61(1): 11-25.
  • 8. Mottet N, van den Bergh RCN, Briers E et al. EAU-ESTRO-ESUR-SIOG Guidelines on Prostate Cancer 2018. In: European Association of Urology Guidelines 2018 Edition [Internet]. Arnhem, The Netherlands: European Association of Urology Guidelines Office; 2018.
  • 9. Dobruch J, Borówka A. „Back bone therapy” w leczeniu chorych na raka stercza opornego na wytrzebienie. Przegląd Urologiczny 2015; 1(89): 28-30.
  • 10. Siddiqui ZA, Krauss DJ. Adjuvant androgen deprivation therapy for prostate cancer treated with radiation therapy. Transl Androl Urol 2018; 7(3): 378-89.
  • 11. Kadar T, Redding TW, Ben-David M et al. Receptors for prolactin, somatostatin, and luteinizing hormone-releasing hormone in experimental prostate cancer after treatment with analogs of luteinizing hormone-releasing hormone and somatostatin. Proc Natl Acad Sci U S A 1988; 85: 890-94.
  • 12. Kakar SS, Musgrove LC, Devor DC et al. Cloning, sequencing, and expression of human gonadotropin releasing hormone (GnRH) receptor. Biochem Biophys Res Commun 1992; 189(1): 289-95.
  • 13. Medycyna Praktyczna Indeks [Internet]. Medycyna Praktyczna; c1996–2019 [cytowane 5 września 2019] [online: https://indeks.mp.pl/leki/subst. php?id=816&rfbl=1].
  • 14. Tornoe CW, Agerso H, Senderovitz T et al. Population pharmacokinetic/pharmacodynamic (PK/PD) modelling of the hypothalamic-pituitary-gonadal axis following treatment with GnRH analogues. Br J Clin Pharmacol 2007; 63(6): 648-64.
  • 15. Klippel KF, Winkler CJ, Jocham D et al. [Effectiveness and tolerance of 1 dosage forms (subcutaneous and intramuscular) of decapeptyl depot in patients with advanced prostate carcinoma]. Urologe A 1999; 38(3): 270-75.
  • 16. Szymańska E, Winnicka K. Nowoczesna postać leku do oczu o kontrolowanym uwalnianiu. Farm Pol 2009; 65(5): 378-86.
  • 17. PubChem compound summary triptorelin [Internet]. US National Library of Medicine – National Center for Biotechnology Information [cytowane 5 września 2019] [online: https://pubchem.ncbi.nlm.nih.gov/compound/Triptorelin#section=Pharmacology].
  • 18. Paz‐Bouza JI, Schor NA, Monje E et al. Histological findings in the rat prostate cancer model during treatment with a luteinizing hormone‐releasing hormone agonist and novantrone. Prostate 1987.
  • 19. Charakterystyka produktu leczniczego Diphereline SR 3,75; 3,75 mg; proszek i rozpuszczalnik do sporządzania zawiesiny o przedłużonym uwalnianiu do wstrzykiwań [online: http://leki.urpl.gov.pl/files/43_Diphereline_SR_3_75_prosz_rozp_sporz_zaw_przedl_uwaln_wstrzyk_3_75_ mg_4869.pdf].
  • 20. Charakterystyka produktu leczniczego Decapeptyl Depot; 3,75 mg; proszek i rozpuszczalnik do sporządzania zawiesiny do wstrzykiwań [online: http://leki.urpl.gov.pl/files/Decapeptyl_Depot_3_75mg.pdf].
  • 21. Charakterystyka produktu leczniczego Diphereline SR 11,25 mg; 11,25 mg; proszek i rozpuszczalnik do sporządzania zawiesiny o przedłużonym uwalnianiu do wstrzykiwań [online: http://leki.urpl.gov.pl/files/43_Diphereline_SR_11_25_mg_prosz_rozp_sporz_zaw_przed_uwaln_wstrzyk_11_25mg.pdf].
  • 22. Charakterystyka produktu leczniczego Diphereline SR 22,5 mg, 22,5 mg, proszek i rozpuszczalnik do sporządzenia zawiesiny do wstrzykiwań, o przedłużonym uwalnianiu [online: https://gdziepolek.blob.core.windows.net/product-documents/doc84495/diphereline-sr-22-5-mg-dokument.pdf].
  • 23. Han J, Zhang S, Liu W et al. An analytical strategy to characterize the pharmacokinetics and pharmacodynamics of triptorelin in rats based on simultaneous LC-MS/MS analysis of triptorelin and endogenous testosterone in rat plasma. Anal Bioanal Chem 2014; 406(9-10): 2457-65.
  • 24. Gonzalez-Barcena D, Perez-Sanchez PL, Graef A et al. Inhibition of the pituitary-gonadal axis by a single intramuscular administration of D-Trp-6-LH-RH (decapeptyl) in a sustained-release formulation in patients with prostatic carcinoma. Prostate 1989; 14(4): 291-300.
  • 25. Romero E, Velez de Mendizabal N, Cendros JM et al. Pharmacokinetic/pharmacodynamic model of the testosterone effects of triptorelin administered in sustained release formulations in patients with prostate cancer. J Pharmacol Exp Ther 2012; 342(3): 788-98.
  • 26. Szende B, Lovász S, Farid P et al. Apoptosis in Prostate Carcinomas after Short-Term Treatment with Decapeptyl. Ann N Y Acad Sci 2003; 1010: 784-88.
  • 27. Lee LT, Schally AV, Liebow C et al. Dephosphorylation of cancer protein by tyrosine phosphatases in response to analogs of luteinizing hormone-releasing hormone and somatostatin. Anticancer Res 2008; 28(5A): 2599-605.
  • 28. Pinski J, Reile H, Halmos G et al. Inhibitory effects of analogs of luteinizing hormone‐releasing hormone on the growth of the androgen‐independent dunning R‐3327‐AT‐1 rat prostate cancer. Int J Cancer 1994. DOI: 10.1002/ijc.2910590112.
  • 29. Jungwirth A, Schally AV, Pinski J et al. Inhibition of in vivo proliferation of androgen-independent prostate cancers by an antagonist of growth hormone-releasing hormone. Br J Cancer 1997; 75(11): 1585-92.
  • 30. Lamharzi N, Halmos G, Jungwirth A et al. Decrease in the level and mRNA expression of LH-RH and EGF receptors after treatment with LH-RH antagonist Cetrorelix in DU-145 prostate tumor xenografts in nude mice. Int J Oncol 1998; 13(3):429-35.
  • 31. Szepeshazi K, Korkut E, Schally AV. Decrease in the AgNOR number in dunning R3327 prostate cancers after treatment with an agonist and antagonist of luteinizing hormone-releasing hormone. Am J Pathol 1991; 138(5): 1273-77.
  • 32. Eicke N, Gunthert AR, Viereck V et al. GnRH-II receptor-like antigenicity in human placenta and in cancers of the human reproductive organs. Eur J Endocrinol 2005; 153(4): 605-12.
  • 33. Schally AV, Redding TW. Somatostatin analogs as adjuncts to agonists of luteinizing hormone-releasing hormone in the treatment of experimental prostate cancer. Proc Natl Acad Sci U S A 1987; 84(20): 7275-9.
  • 34. Qayum A, Waxman J, Gullick W et al. The effects of gonadotrophin releasing hormone analogues in prostate cancer are mediated through specific tumour receptors. Br J Cancer 1990; 62(1): 96-9.
  • 35. Redding TW, Schally AV. Inhibition of the pituitary-gonadal axis in nude male mice by continuous administration of LHRH agonists and antagonists. J Endocrinol 1990; 126(2): 309-15.
  • 36. Milovanovic SR, Radulovic S, Groot K et al. Inhibition of growth of PC‐82 human prostate cancer line xenografts in nude mice by bombesin antagonist RC‐3095 or combination of agonist [D‐Trp6]‐luteinizing hormone‐releasing hormone and somatostatin analog RC‐160. Prostate 1992; 20(4): 269-80.
  • 37. Paz‐Bouza JI, Schor NA, Monje E et al. Histological findings in the rat prostate cancer model during treatment with a luteinizing hormone‐releasing hormone agonist and novantrone. Prostate 1987; 10(4): 291-302.
  • 38. Zalatnai A, Paz‐Bouza JI, Redding TW et al. Histologic changes in the rat prostate cancer model after treatment with somatostatin analogs and D‐ Trp‐6‐LH‐RH. Prostate 1988; 12(1): 85-98.
  • 39. Hellstrom M, Ranefall P, Wester K et al. Effect of androgen deprivation on epithelial and mesenchymal tissue components in localized prostate cancer. Br J Urol. 1997; 79(3): 421-6.
  • 40. Boccardo F, Giuliani L, Santi L. D-Trp-6-LH-RH treatment of advanced prostatic cancer. (London, England) 1986; 1: 621.
  • 41. Boccardo F, Decensi A, Guarneri D et al. Long-term results with a long-acting formulation of D-TRP-6 LH-RH in patients with prostate cancer: an Italian prostatic cancer project (P.O.N.CA.P.) study. Prostate 1987; 11(3): 243-55.
  • 42. Rolandi E, Franceschini R, Giberti C et al. Sustained impairment of pituitary and testicular function in prostatic cancer patients treated with a depot form of a GnRH agonist. Horm Res 1988; 30(1): 22-5.
  • 43. Bouchot O, Soret JY, Jacqmin D et al. Three-month sustained-release form of triptorelin in patients with advanced prostatic adenocarcinoma: results of an open pharmacodynamic and pharmacokinetic multicenter study. Horm Res 1998; 50(2): 89-93.
  • 44. Teillac P, Heyns CF, Kaisary AV et al. Pharmacodynamic equivalence of a decapeptyl 3-month SR formulation with the 28-day SR formulation in patients with advanced prostate cancer. Horm Res 2004; 62(5): 252-8.
  • 45. Lundstrom EA, Rencken RK, van Wyk JH et al. Triptorelin 6-month formulation in the management of patients with locally advanced and metastatic prostate cancer: an open-label, non-comparative, multicentre, phase III study. Clin Drug Investig 2009; 29(12): 757-65.
  • 46. Zlotta A, Debruyne FMJ. Expert opinion on optimal testosterone control in prostate cancer. Eur Urol Suppl 2005; 4(8): 37-41.
  • 47. Lebret T, Rouanne M, Hublarov O et al. Efficacy of triptorelin pamoate 11.25 mg administered subcutaneously for achieving medical castration levels of testosterone in patients with locally advanced or metastatic prostate cancer. Ther Adv Urol 2015; 7(3): 125-34.
  • 48. Breul J, Lundstrom E, Purcea D et al. Efficacy of Testosterone Suppression with Sustained-Release Triptorelin in Advanced Prostate Cancer. Adv Ther 2017; 34(2): 513-23.
  • 49. Kao CC, Chang YH, Wu T et al. Open, multi-center, phase IV study to assess the efficacy and tolerability of triptorelin in Taiwanese patients with advanced prostate cancer. J Chin Med Assoc 2012; 75(6): 255-61.
  • 50. Klippel KF, Winkler CJ, Jocham D et al. [Effectiveness and tolerance of 1 dosage forms (subcutaneous and intramuscular) of decapeptyl depot in patients with advanced prostate carcinoma]. Urologe A 1999; 38(3): 270-5.
  • 51. Martinez-Pineiro L, Schalken JA, Cabri P et al. Evaluation of urinary prostate cancer antigen-3 (PCA3) and TMPRSS2-ERG score changes when starting androgen-deprivation therapy with triptorelin 6-month formulation in patients with locally advanced and metastatic prostate cancer. BJU Int 2014; 114(4): 608-16.
  • 52. de la Taille A, Martinez-Pineiro L, Cabri P et al. Factors predicting progression to castrate-resistant prostate cancer in patients with advanced prostate cancer receiving long-term androgen-deprivation therapy. BJU Int 2017; 119(1): 74-81.
  • 53. Heidenreich A, Porres D, Epplen R et al. [Change of the LHRH analogue in progressive castration-refractory prostate cancer]. Urologe A 2012; 51(9): 1282-7.
  • 54. Calais da Silva F, Calais da Silva FM, Goncalves F et al. Locally advanced and metastatic prostate cancer treated with intermittent androgen monotherapy or maximal androgen blockade: results from a randomised phase 3 study by the South European Uroncological Group. Eur Urol 2014; 66(2): 232-9.
  • 55. Mathe G, Schally AV, Comaru-Schally AM et al. Phase II trial with D-Trp-6-LH-RH in prostatic carcinoma: comparison with other hormonal agents. Prostate 1986; 9(4): 327-42.
  • 56. Parmar H, Phillips RH, Lightman SL et al. Early tumor exacerbation in patients treated with long acting analogues of gonadotrophin releasing hormone. British Medical Journal (Clinical research ed.) 1985; 291: 1645.
  • 57. Parmar H, Edwards L, Phillips RH et al. Orchiectomy versus long-acting D-Trp-6-LHRH in advanced prostatic cancer. Br J Urol 1987; 59(3): 248-54.
  • 58. Parmar H, Phillips RH, Lightman SL et al. How would you like to have an orchidectomy for advanced prostatic cancer? Am J Clin Oncol 1988; 11 Suppl 2: S160-8.
  • 59. Ostergren PB, Kistorp C, Fode M et al. Luteinizing Hormone-Releasing Hormone Agonists are Superior to Subcapsular Orchiectomy in Lowering Testosterone Levels of Men with Prostate Cancer: Results from a Randomized Clinical Trial. J Urol 2017; 197(6): 1441-7.
  • 60. Bolton EM, Lynch T. Are all gonadotrophin-releasing hormone agonists equivalent for the treatment of prostate cancer? A systematic review. BJU Int 2018; 122(3): 371-83.
  • 61. Kuhn JM, Abourachid H, Brucher P et al. A randomized comparison of the clinical and hormonal effects of two GnRH agonists in patients with prostate cancer. Eur Urol 1997; 32(4): 397-403.
  • 62. Abbou CC, Lucas C, Leblanc V. [Tolerance and clinical and biological responses during the first 6 months of treatment with 1-month sustained release LHRH agonists leuprolerin and triptolerin in patients with metastatic prostate cancer]. Prog Urol 1997; 7(6): 984-95.
  • 63. Heyns CF, Simonin MP, Grosgurin P et al. Comparative efficacy of triptorelin pamoate and leuprolide acetate in men with advanced prostate cancer. BJU Int 2003; 92(3): 226-31.
  • 64. Crawford ED, Phillips JM. Six-month gonadotropin releasing hormone (GnRH) agonist depots provide efficacy, safety, convenience, and comfort. Cancer Manag Res 2011; 3: 201-9.
  • 65. Shim M, Bang WJ, Oh CY et al. Effectiveness of three different luteinizing hormone-releasing hormone agonists in the chemical castration of patients with prostate cancer: Goserelin versus triptorelin versus leuprolide. Investig Clin Urol 2019; 60(4): 244-50.
  • 66. Uttley L, Whyte S, Gomersall T et al. Degarelix for Treating Advanced Hormone-Dependent Prostate Cancer: An Evidence Review Group Perspective of a NICE Single Technology Appraisal. Pharmacoeconomics 2017; 35(7): 717-26.
  • 67. Hedlund PO, Henriksson P. Parenteral estrogen versus total androgen ablation in the treatment of advanced prostate carcinoma: effects on overall survival and cardiovascular mortality. The Scandinavian Prostatic Cancer Group (SPCG)-5 Trial Study. Urology 2000; 55(3): 328-33.
  • 68. Dalesio O, Van Tinteren H, Clarke M et al. Maximum androgen blockade in advanced prostate cancer: An overview of the randomised trials. Lancet 2000; 355: 1491-8.
  • 69. Labrie F, Dupont A, Giguere M et al. Combination therapy with flutamide and castration (orchiectomy or LHRH agonist): the minimal endocrine therapy in both untreated and previously treated patients. J Steroid Biochem 1987; 27(1–3): 525-32.
  • 70. Spetz AC, Hammar M, Lindberg B et al. Prospective evaluation of hot flashes during treatment with parenteral estrogen or complete androgen ablation for metastatic carcinoma of the prostate. Prospective evaluation of hot flashes during treatment with parenteral estrogen or complete androgen ablation for metastatic carcinoma of the prostate. J Urol 2001; 166(2): 517-20.
  • 71. Kintzel PE, Chase SL, Schultz LM et al. Increased risk of metabolic syndrome, diabetes mellitus, and cardiovascular disease in men receiving androgen deprivation therapy for prostate cancer. Pharmacotherapy 2008; 28(12): 1511-22.
  • 72. Hedlund PO, Johansson R, Damber JE et al. Significance of pretreatment cardiovascular morbidity as a risk factor during treatment with parenteral oestrogen or combined androgen deprivation of 915 patients with metastasized prostate cancer: evaluation of cardiovascular events in a randomized trial. Scand J Urol Nephrol 2011; 45(5): 346-53.
  • 73. Moorjani S, Dupont A, Labrie F et al. Changes in plasma lipoproteins during various androgen suppression therapies in men with prostatic carcinoma: effects of orchiectomy, estrogen, and combination treatment with luteinizing hormone-releasing hormone agonist and flutamide. J Clin Endocrinol Metab 1988; 66(2): 314-22.
  • 74. Ostergren PB, Kistorp C, Fode M et al. Metabolic consequences of gonadotropin-releasing hormone agonists vs orchiectomy: a randomized clinical study. BJU Int 2019; 123(4): 602-11.
  • 75. Maillefert JF, Sibilia J, Michel F et al. Bone mineral density in men treated with synthetic gonadotropin-releasing hormone agonists for prostatic carcinoma. J Urol 1999; 161(4): 1219-22.
  • 76. Smith MR, Boyce SP, Moyneur E et al. Risk of clinical fractures after gonadotropin-releasing hormone agonist therapy for prostate cancer. J Urol 2006; 175(1): 136-9; discussion 139.
  • 77. Lehrer S, Rheinstein PH, Rosenzweig KE. No Relationship of Anti-Androgens to Alzheimer’s Disease or Cognitive Disorder in the MedWatch Database. J Alzheimer’s Dis reports 2018; 2(1): 123-7.
  • 78. Oefelein MG, Feng A, Scolieri MJ et al. Reassessment of the definition of castrate levels of testosterone: Implications for clinical decision making. Urology 2000; 56(6): 1021-4.
  • 79. Perachino M, Cavalli V, Bravi F. Testosterone levels in patients with metastatic prostate cancer treated with luteinizing hormone-releasing hormone therapy: prognostic significance? BJU Int 2010; 105(5): 648-51.
  • 80. Klotz L, O’Callaghan C, Ding K et al. Nadir testosterone within first year of androgen-deprivation therapy (ADT) predicts for time to castration-resistant progression: A secondary analysis of the PR-7 trial of intermittent versus continuous ADT. J Clin Oncol 2015; 33(10): 1151-6.
  • 81. Morote J, Orsola A, Planas J et al. Redefining Clinically Significant Castration Levels in Patients With Prostate Cancer Receiving Continuous Androgen Deprivation Therapy. J Urol 2007; 178(4 Pt 1): 1290-5.
  • 82. Omasits U, Ahrens CH, Müller S et al. Protter: interactive protein feature visualization and integration with experimental proteomic data. Bioinformatics 2014; 30: 884-86.
Document Type
article
Publication order reference
Identifiers
YADDA identifier
bwmeta1.element.psjd-e4bd1e67-2d4e-46e7-880c-626de18569cd
JavaScript is turned off in your web browser. Turn it on to take full advantage of this site, then refresh the page.