Triptorelin in androgen depravation therapy of advanced prostate cancer Review article
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Published:
Dec 31, 2019
Keywords:
advanced prostate cancer, androgen depravation therapy, triptorelin
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Abstract
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.
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Kozikowski M, Dobruch J. Triptorelin in androgen depravation therapy of advanced prostate cancer. OncoReview [Internet]. 2019Dec.31 [cited 2024Jul.23];9(4(36):73-7. Available from: https://journalsmededu.pl/index.php/OncoReview/article/view/1083
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ENDOCRINOLOGY IN ONCOLOGY
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Copyright: © Medical Education sp. z o.o. This is an Open Access article distributed under the terms of the Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). License (https://creativecommons.org/licenses/by-nc/4.0/), allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.
Address reprint requests to: Medical Education, Marcin Kuźma (marcin.kuzma@mededu.pl)
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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.
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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.
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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.
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17. PubChem compound summary triptorelin. US National Library of Medicine – National Center for Biotechnology Information. Online: https://pubchem.ncbi.nlm.nih.gov/compound/Triptorelin#section=Pharmacology (Access: 5.092019).
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. http://doi.org/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.
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