РОЛЬ ДЕГАРЕЛИКСА (ФИРМАГОН) В ЛЕЧЕНИИ РАСПРОСТРАНЕННОГО РАКА ПРЕДСТАТЕЛЬНОЙ ЖЕЛЕЗЫ: МОЖНО ЛИ УЛУЧШИТЬ КАЧЕСТВО КАСТРАЦИОННОЙ ТЕРАПИИ?
https://doi.org/10.17650/1726-9776-2011-7-1-66-72
Аннотация
Дегареликс (Фирмагон, Ферринг Фармасьютикалс) – новый антагонист гонадотропин-рилизинг-гормона (ГнРГ), разрешенный и одобренный к применению при распространенном гормонозависимом раке предстательной железы. Рекомендовано вводить препарат под кожу живота в начальной дозе 240 мг и ежемесячно в поддерживающей дозе 80 мг. В рандомизированном исследовании III фазы продемонстрировано преимущество дегареликса в отношении скорости снижения тестостерона до кастрационного уровня, темпа уменьшения уровня простатического специфического антигена (ПСА), а также отсутствия инициального повышения и колебаний концентрации андрогенов в процессе лечения по сравнению с агонистом ГнРГ лейпрорелином. При наблюдении в течение 1 года установлено, что риск возникновения ПСА-рецидива и смерти достоверно выше при использовании лейпрорелина по сравнению с таковым при применении дегареликса. При переводе больных, получавших лейпрорелин, на терапию дегареликсом отмечено достоверное снижение риска развития ПСА-рецидива. Частота случаев возникновения нежелательных явлений и отмены лечения на фоне терапии дегареликсом не отличается от данных показателей в группе лейпрорелина. Для формирования окончательных выводов необходимо проведение исследований с длительными сроками наблюдения за больными.
Об авторах
В. Б. Матвеев
Отделение урологии РОНЦ им. Н.Н. Блохина РАМН, Москва
Россия
Россия
М. И. Волкова
Отделение урологии РОНЦ им. Н.Н. Блохина РАМН, Москва
Россия
Россия
Список литературы
1. Huggins C., Hodges C.V. Studies on prostatic cancer: effect of castration, of estrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate. Cancer Res 1941;1:293–7.
2. Labrie C., Belanger A., Labrie F. Androgenic activity of dehydroepiandrosterone and androstenedione in the rat ventral prostate. Endocrinology 1988;123:1412–7.
3. Van Poppel H., Nilsson S. Testosterone surge: rationale for gonadotropin-releasing hormone blockers? Urology 2008; 71:1001–6.
4. Oranusi C.K., Nwofor A.M.E. Evaluation of surgical castration for prostate cancer at Nnewi: issues regarding follow-up of cases. Tropic J Med Res 2008;12(1):38–41.
5. The Veterans Administration Cooperative Urological Research Group. Surg Gynecol Obstet 1967;124:1011–7.
6. Robinson M.R., Smith P.H., Richards B. et al. The final analysis of the EORTC Genito-Urinary Tract Cancer Cooperative Group Phase III clinical trial (Protocol 30805) comparing orchidectomy, orchidectomy plus cyproterone acetate, and low dose stilboestrol in the management of metastatic carcinoma of the prostate. Eur Urol 1995;28:273–83.
7. Heidenreich A., Aus G., Bolla M. et al. EAU guidelines on prostate cancer. Eur Urol 2008;53:68–80.
8. Berges R. Eligard: pharmacokinetics, effect on testosterone and PSA levels and tolerability. Eur Urol Suppl 2005;4:20–5.
9. Kuhn J.M., 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.
10. Vogelzang N.J., Chodak G.W., Soloway M.S. et al. Goserelin versus orchiectomy in the treatment of advanced prostate cancer: final results of a randomized trial. Zoladex Prostate Study Group. Urology 1995;46(2):220–6.
11. Kaisary A.V., Tyrrell C.J., Peeling W.B. et al. Comparison of LHRH analogue (ZOLADEX) with orchiectomy in patients with metastatic prostatic carcinoma. Br J Urol 1991;67:502–8.
12. Anderson J., Abrahamsson P.-A., Crawford D. et al. Management of advanced prostate cancer: can we improve on androgen deprivation therapy? Int BJU 2008;101:1497–501.
13. Lin B.J., Chen K.K., Chen M.T., Chang L.S. The time for serum testosterone to reach castrate level after bilateral orchidectomy or oral estrogen in the management of metastatic prostatic cancer. Urology 1994;43:834–77.
14. Sasagawa I., Kubota Y., Nakada T. et al. Influence of luteinizing hormonereleasing hormone analogues on serum levels of prostatic acid phosphatase and prostatic specific antigen in patients with metastatic carcinoma of the prostate. Int Urol Nephrol 1998;30:745–5317.
15. Bubley G.J. Is the flare phenomenon clinically significant? Urology 2001;58 (Suppl 1):5–9.
16. Ziment Group. Market Research Data in five European countries. Commissioned by Ferring – data on file (not in public domain), 2006.
17. Oefelein M.G., Feng A., Scolieri M.J. et al. Reassessment of the definition of castrate levels of testosterone: implications for clinical decision making. Urology 2000;56:1021–4.
18. Lin B.J., Chen K.K., Chen M.T., Chang L.S. The time for serum testosterone to reach castrate level after bilateral orchidectomy or oral estrogen in the management ofmetastatic prostatic cancer. Urology 1994;43:834–7.
19. Oefelein M.G., 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 2000;164:726–9.
20. 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;58:756–61.
21. Esquena S., Abascal J.M., Trilla E., Morote J. Failure of luteinising hormonal releasing hormonal agonist therapy to achieve castration. Does it exist? Eur Urol Suppl 2004;3:57;abstr 218.
22. Wechsel H.W., Zerbib M., Pagano F., Coptcoat M.J. Randomized open labeled comparative study of the efficacy, safety and tolerability of leuprorelin acetate 1M and 3M depot in patients with advanced prostatic cancer. Eur Urol 1996;30(Suppl 1):7–14.
23. Kawakami J., Morales A. A comprehensive hormonal evaluation in patients with cancer of the prostate on androgen suppression with LHRH agonists. J Urol 2002;167(Suppl 4):288.
24. Zinner N.R., Bidair M., Centeno A., Tomera K. 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 2004;64:1177–81.
25. Sharifi R., Browneller R. Serum testosterone suppression and potential for agonistic stimulation during chronic treatment with monthly and 3-month depot formulations of leuprolide acetate for advanced prostate cancer. J Urol 2002;168:1001–4.
26. Morote J., Planas J., Raventos C.X. et al. Redefining clinically significant castration levels in patients with prostate cancer receiving continuous androgen deprivation therapy. J Urol 2007;178:1290–5.
27. Hocart S.J., Nekola M.V., Coy D.H. Effect of reductive alkylation of D-lysine in position 6 on the histamine-releasing activity of luteinizing hormone-releasing hormone antagonists. J Med Chem 1987;30:739–43.
28. Flouret G., Mahan K., Majewski T. Decreased histamine release by luteinizing hormone-releasing hormone antagonists obtained upon translocation of the cationic amino acid from position 8 to position 7. J Med Chem 1992;35:636–40.
29. Bagatell C.J., Conn P.M., Bremner W.J. Single-dose administration of the gonadotropin-releasing hormone antagonist, Nal-Lys (antide) to healthy men. Fertil Steril 1993;60:680–5.
30. Bagatell C.J., Rivier J.E., Bremner W.J. Dose effects of the gonadotropinreleasing hormone antagonist, Nal-Glu, combined with testosterone enanthate on gonadotropin levels in normal men. Fertil Steril 1995;64:139–45.
31. Plenaxis T.M. Abarelix for injectable suspension. Product description. Available at: http://www.fda.gov/Cder/foi/label/2003/021320lbl.pdf (accessed 21 August 2008).
32. Broqua P., Riviere P.J., Conn P.M. et al. Pharmacological profile of a new, potent, and long-acting gonadotropin-releasing hormone antagonist: degarelix. J Pharmacol Exper Ther 2002;301(1):95–102.
33. http://regulatoryaffairs.pharmaceuticalbusinessreview.com/news/astellaspharma-files-degarelix-acetate-maa-tomhlw-_291010
34. Van Poppel H., Tombal B., de la Rosette J.J. et al. Degarelix: a novel gonadotropinreleasing 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):805–13.
35. Gittelman M., Pommerville P.J., Persson B.E. et al; Degarelix Study Group. 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):1986–92.
36. Инструкция к препарату Фирмагон. 37. Princivalle M., Broqua P., White R. 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 Exper Ther 2007; 320(3):1113–8.
37. Klotz L., Boccon-Gibod L., Shore N.D. 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):1531–8.
38. 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;57:836–42.
39. Crawford E.D., Moul J.W., Shore N.D. et al. Switching from leuprolide to degarelix vs continuous degarelix treatment – effects on long-term prostatespecific antigen control. Poster and abstract presentation at the AUA 2010 Annual Meeting, San Francisco, CA, USA. J Urol 2010;183(Suppl):262;abstr 670
40. Schröder Fritz H., Tombal B., Miller K. 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):182–7.
41. Debruyne F., Bhat G., Garnick M.B. Abarelix for injectable suspension: firstin-class gonadotropin-releasing hormone antagonist for prostate cancer. Future Oncol 2006;2:677–96.
Рецензия
Для цитирования:
Матвеев В.Б., Волкова М.И. РОЛЬ ДЕГАРЕЛИКСА (ФИРМАГОН) В ЛЕЧЕНИИ РАСПРОСТРАНЕННОГО РАКА ПРЕДСТАТЕЛЬНОЙ ЖЕЛЕЗЫ: МОЖНО ЛИ УЛУЧШИТЬ КАЧЕСТВО КАСТРАЦИОННОЙ ТЕРАПИИ? Онкоурология. 2011;7(1):66-72. https://doi.org/10.17650/1726-9776-2011-7-1-66-72
For citation:
Matveev V.B., Volkova M.I. ROLE OF DEGARELIX (FIRMAGON) IN THE TREATMENT OF DISSEMINATED PROSTATE CANCER: CAN THE QUALITY OF CASTRATION THERAPY BE IMPROVED? Cancer Urology. 2011;7(1):66-72. (In Russ.) https://doi.org/10.17650/1726-9776-2011-7-1-66-72
Просмотров:
2353
Послать статью по эл. почте 
