Новые лекарственные препараты в терапии рака предстательной железы, резистентного к кастрации

Читать PDF

Аннотация

Рак предстательной железы (РПЖ) – одно из наиболее распространенных злокачественных новообразований у мужчин в России.
В лечении больных метастатическим РПЖ основное место занимает гормонотерапия, при помощи которой удается достичь лечебного эффекта у большинства пациентов. Однако у подавляющего числа этих больных рано или поздно наступает прогрессирование и развивается гормонорезистентный РПЖ (ГРРПЖ). В настоящее время эффективность схем химиотерапии ГРРПЖ остается низкой. В 2004 г. в двух рандомизированных исследованиях впервые было показано увеличение выживаемости на фоне химиотерапии доцетакселом по сравнению с митоксантроном у больных ГРРПЖ. Целью современных клинических исследований является улучшение показателей выживаемости пациентов, страдающих ГРРПЖ. В обзоре представлены данные о новых классах препаратов и современных клинических исследованиях, направленных на улучшение результатов лечения данной категории больных.

Ключевые слова: гормонорезистентный рак предстательной железы, таргетная терапия, иммунотерапия, доцетаксел, абиратерона ацетат.

________________________________________________

Prostate cancer is one of the most common cancers in men in Russia. Although the majority of patients with metastatic prostate cancer initially respond to androgen deprivation therapy, almost all patients will eventually progress to develop castration-resistant prostate cancer (CRPC). Treatment options for CRPC remain limited. In 2004 two large randomized clinical trials demonstrated for the first time a small but significant survival advantage of docetaxel-based chemotherapy compared with mitoxantrone in patients with metastatic CRPC. Clinical trials in hormone-refractory prostate cancer are now focused on the survival improvement seen with docetaxel-based therapy. This article presents a summary of some of the more promising treatments and regimens for advanced prostate cancer and focuses on the key clinical trials of various treatment options of CRPC currently in use and under investigation.

Key words: castration-resistant prostate cancer, abiraterone acetate, target therapy, immunotherapy, docetaxel.

Полный текст

Материалы доступны только для специалистов сферы здравоохранения. Авторизуйтесь или зарегистрируйтесь.

Список литературы

1. Попова О.П., Шегай П.В., Иванов А.А. и др. Молекулярные механизмы развития рака предстательной железы: корреляция уровней EGF, HGF и VEGF с показателями гормональной рефрактерности. Молекулярная медицина. 2009; 3: 38–44.
2. Русаков И.Г., Соков Д.Г. Эффективность бисфосфонатов в лечении метастазов рака предстательной железы в кости скелета. Фарматека. 2008; 18: 41–6.
3. Abdulla A, Kapoor A. Emerging novel therapies in the treatment of castrate-resistant prostate cancer. Can Urol Assoc J 2011; 5 (2): 120–33.
4. Armstrong AJ, Creel P, Turnbull J et al. A phase I–II study of docetaxel and atrasentan in men with castration-resistant metastatic prostate cancer. Clin Cancer Res 2008; 14: 6270–6.
5. Bagnato A, Natali PG. Endothelin receptors as novel targets in tumor therapy. J Trans Med 2004; 2: 16.
6. Banerji U. Heat shock protein 90 as a drug target: some like it hot. Clin Cancer Res 2009; 15: 9–14.
7. Beer TM, Slovin SF, Higano CS et al. Phase I trial of ipilimumab (IPI) alone and in combination with radiotherapy (XRT) in patients with metastatic castration resistant prostate cancer (mCRPC). J Clin Oncol 2008; 26 (Suppl.). Abstr. 5004.
8. Berthold DR, Pond G, DeWit R et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer: updated survival of the TAX327 study. Proc ASCO Prostate Cancer Symposium 2007. Abstr. 147.
9. Bone HG, Bolognese MA, Yuen CK et al. Effects of denosumab on bone mineral density and bone turnover in postmenopausal women. J Clin Endocrinol Metab 2008; 93: 2149–57.
10. Carducci MA, Jimeno A. Targeting bone metastasis in prostate cancer with endothelin receptor antagonists. Clin Cancer Res 2006; 12: 6296–300.
11. Chi KN, Hotte SJ, Yu E et al. A randomized phase II study of OGX-011 in combination with docetaxel and prednisone or docetaxel and prednisone alone in patients with metastatic hormone refractory prostate cancer (HRPC). J Clin Oncol 2007; 25. Abstr. 5069.
12. Curwen J, Hughes G, Hickinson M et al. The impact of ZD4054, a specific endothelin A receptor antagonist, on tumor blood supply, invasion, and the bone microenvironment. Mol Cancer Ther 2007; 6 (Suppl.): 153–4.
13. Danila DC, Morris MJ, de Bono JS et al. Phase II multicentre study of abiraterone acetate plus prednisone therapy in patients with docetaxel-treated castration-resistant prostate cancer. J Clin Oncol 2010; 28: 1496–501.
14. Ellis GK, Bone HG, Chlebowski R et al. Randomized trial of denosumab in patients receiving adjuvant aromatase inhibitors for nonmetastatic breast cancer. J Clin Oncol 2008; 26: 4875–82.
15. Fizazi K, Carducci M, Smith M et al. Denosumab compared with zoledronic acid for the treatment of bone metastases in patients with castration resistant prostate cancer. J Clin Oncol 2010; 28. Abstr. LBA4507.
16. Fossa SD, Slee PH, Brausi M et al. Flutamide versus prednisone in patients with prostate cancer symptomatically progressing after androgen-ablative therapy: a phase III study of the European Organization for Research and Treatment of Cancer Genitourinary Group. J Clin Oncol 2001; 19: 62–71.
17. George DJ, Halabi S, Shepard TF et al. Prognostic significance of plasma vascular endothelial growth factor levels in patients with hormone-refractory prostate cancer treated on Cancer and Leukemia Group B 9480. Clin Cancer Res 2001; 7: 1932–6.
18. Heath EI, Hillman DW, Vaishampayan U et al. A phase II trial of 17-allylamino-17-demethoxygeldanamycin in patients with hormone-refractory metastatic prostate cancer. Clin Cancer Res 2008; 14: 7940–6.
19. Isambert N, Freyer G, Zanetta S et al. A phase I dose escalation and pharmacokinetic (PK) study of intravenous aflibercept (VEGF Trap) plus docetaxel (D) in patients (pts) with advanced solid tumors: Preliminary results. J Clin Oncol 2008; 26. Abstr. 3599.
20. Jain RK, Tong RT, Munn LL. Effect of vascular normalization by antiangiogenic therapy on interstitial hypertension, peritumor edema, and lymphatic metastasis: insights from a mathematical model. Cancer Res 2007; 67: 2729–35.
21. Kantoff PW, Higano CS, Shore ND et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med 2010; 363: 411–22.
22. Leach DR, Krummel MF, Allison JP. Enhancement of antitumor immunity by CTLA-4 blockade. Science 1996; 271: 1734–6.
23. Linja MJ, Savinainen KJ, Saramaki OR et al. Amplification and overexpression of androgen receptor gene in hormone-refractory prostate cancer. Cancer Res 2001; 61: 3550–5.
24. McVicar GR, Kuzel TM, Curti BD et al. An open-label, multicenter, phase I–II study of AT-101 in combination with docetaxel (D) and prednisone (P) in men with hormone refractory prostate cancer (HRPC). J Clin Oncol 2008 (Suppl.). Abstr. 16043.
25. Miayake H, Tolcher A, Gleave ME. Chemosensitization and delayed androgen-independent recurrence of prostate cancer with the use of antisense Bcl-2 oligodeoxynucleotides. J Natl Cancer Inst 2000; 92: 34–41.
26. Miyake H, Nelson C, Rennie PS, Gleave ME. Testosterone-repressed prostate message-2 is an antiapoptotic gene involved in progression to androgen independence in prostate cancer. Cancer Res 2000; 606: 170–6.
27. Nam S, Kim D, Cheng JQ et al. Action of the Src family kinase inhibitor, dasatinib (BMS-354825), on human prostate cancer cells. Cancer Res 2005; 65: 9185–9.
28. Nelson JB, Love W, Chin JL et al. Phase 3, randomized, controlled trial of atrasentan in patients with nonmetastatic, hormone-refractory prostate cancer. Cancer 2008; 113: 2478–87.
29. Picus J, Halabi S, Rini B et al. The use of bevacizumab (B) with docetaxel (D) and estramustine (E) in hormone refractory prostate cancer (HRPC): initial results of CALGB 90006. Proc Am Soc Clin Oncol 2003; 22. Abstr. 1578.
30. Robertson CN, Roberson KM, Padilla GM et al. Induction of apoptosis by diethylstilbestrol in hormone-insensitive prostate cancer cells. J Natl Cancer Inst 1996; 88: 908–17.
31. O'Day S, Hodi FS, McDermott DF et al. A phase III, randomized, double-blind, multicenter study comparing monotherapy with ipilimumab or gp100 peptide vaccine and the combination in patients with previously treated, unresectable stage III or IV melanoma. J Clin Oncol 2010; 28: 7.
32. Schellhammer P. Combined androgen blockade for the treatment of metastatic carcinoma of the prostate. Urology 1996; 47: 622–8.
33. Small EJ, Fratesi P, Reese DM et al. Immunotherapy of hormonerefractory prostate cancer with antigen-loaded dendritic cells. J Clin Oncol 2000; 18: 3894–903.
34. Snoek R, Cheng H, Margiotti K et al. In vivo knockdown of the androgen receptor results in growth inhibition and regression of well-established, castration-resistant prostate tumors. Clin Cancer Res 2009; 15: 39–47.
35. Sternberg CN, Dumez H, Van Poppel H et al. Docetaxel plus oblimersen sodium (Bcl-2 antisense oligonucleotide): an EORTC multicenter, randomized phase II study in patients with castration-resistant prostate cancer. Ann Oncol 2009; 20 (7): 1264–9.
36. Warren R, Liu G. ZD4054: a specific endothelin A receptor antagonist with promising activity in metastatic castration-resistant prostate cancer. Exp Opin Invest Drugs 2008; 17: 1237–45.
37. Tsujimoto Y, Cossman J, Jaffe E, Croce CM. Involvement of the bcl-2 gene in human follicular lymphoma. Science 1985; 228: 1440–3.
38. Yamanaka K, Rocchi P, Miyake H et al. A novel antisense oligonucleotide inhibiting several antiapoptotic Bcl-2 family members induces apoptosis and enhances chemosensitivity in androgenindependent human prostate cancer PC3 cells. Mol Cancer Ther 2005; 4: 1689–98.
39. Yang JC, Haworth L, Sherry RM et al. A randomized trial of bevacizumab, an antivascular endothelial growth factor antibody, for metastatic renal cancer. N Engl J Med 2003; 349: 427–34.
40. Zhang H, Kim JK, Edwards CA et al. Clusterin inhibits apoptosis by interacting with activated Bax. Nat Cell Biol 2005; 7: 909–15.
41. Small EJ et al. Antiandrogen withdrawal alone or in combination with ketoconazole in androgen-independent prostate cancer patients: A phase III trial (CALGB 9583). J of Clinical Oncology 2004; 22 (6).
42. De Bono J et al. The new England J of Medicine 2011; 364 (21).

Авторы

С.Б.Петров1, А.К.Носов1, Н.А.Воробьев2

1 ФГУ НИИ онкологии им. Н.Н.Петрова Минздравсоцразвития РФ, Санкт-Петербург;
2 ГОУ ДПО Санкт-Петербургская медицинская академия последипломного образования Федерального агентства по здравоохранению и социальному развитию

________________________________________________

S.B.Petrov1, A.K.Nosov1, N.A.Vorobeyv2

1 N.N.Petrov Science Research Clinical institute of Oncology of Russian Health Ministry;
2 St.-Petersburg Medical Academy postgraduate Education

Назад к списку

Цель портала OmniDoctor – предоставление профессиональной информации врачам, провизорам и фармацевтам.