ПОСЛЕДОВАТЕЛЬНАЯ ТЕРАПИЯ МЕТАСТАТИЧЕСКОГО КАСТРАЦИОННО-РЕЗИСТЕНТНОГО РАКА ПРЕДСТАТЕЛЬНОЙ ЖЕЛЕЗЫ: НОВЫЕ ВОЗМОЖНОСТИ

В настоящее время в арсенале врача имеется целый ряд лекарственных препаратов, позволяющих увеличить продолжительность жизни больных кастрационно-резистентным раком предстательной железы (КРРПЖ). Большинство из них разрешены для применения в 1-й линии терапии и признаются потенциально равно эффективными ввиду отсутствия их прямого сравнения. Пациенты, страдающие КРРПЖ, нуждаются в непрерывном лечении для сдерживания прогрессирования заболевания, что требует последовательного применения терапевтических агентов. Современные стандарты и рекомендации не дают четкого алгоритма по назначению лечения, поэтому необходим индивидуальный подход в каждом конкретном случае с учетом разнообразных факторов от характера предшествующей терапии до предпочтений пациента. В настоящей статье рассмотрены роль наиболее значимых факторов, влияющих на выбор терапии, и способы оптимизации терапии КРРПЖ в приложении к установленным стандартам лечения и с учетом списка разрешенных в России препаратов.

1. Kirby M., Hirst C., Crawford E.D. Characterising the castration-resistant prostate cancer population: a systematic review. Int J Clin Pract 2011;65(11):1180–92. DOI: 10.1111/j.1742-1241.2011.02799.x. PMID: 21995694.

2. Afshar-Oromieh A., Avtzi E., Glesel F.L. et al. The diagnostic value of PET/CT imaging with the (68)Ga-labelled PSMA ligand HBED-CC in the diagnosis of recurrent prostate cancer. Eur J Nucl Med Mol Imaging 2015;42(2):197–209. DOI: 10.1007/s00259-014-2949-6. PMID: 25411132.

3. Ceci F., Uprimny C., Nilica B. et al. (68) Ga-PSMA PET/CT for restaging recurrent prostate cancer: which factors are associated with PET/CT detection rate. Eur J Nucl Med Mol Imaging 2015;42(8):1284–94. DOI: 10.1007/s00259-015-3078-6. PMID: 25975367.

4. Petrylak D.P., Tangen C.M., Hussain M.H. et al. Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Eng J Med 2004;351(15):1513–20. DOI: 10.1056/NEJMoa041318. PMID: 15470214.

5. Tannock I.F., de Wit R., Berry W.R. et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Eng J Med 2004;351(15):1502–12. DOI: 10.1056/NEJMoa040720. PMID: 15470213.

6. Mottet N., van den Bergh R.C.N., Briers E. EAU–ESTRO–ESUR–SIOG Guidelines on Prostate Cancer. European Association of Urology 2017. P. 145.

7. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines)/Prostate cancer/version 4.2018. August 15, 2018. Available at: https://www.nccn.org/professionals/physician_gls/pdf/prostate.pdf

8. Suominen M.I., Fagerlund K.M., Rissanen J.P. et al. Radium-223 inhibits osseous prostate cancer growth by dual targeting of cancer cells and bone microenvironment in mouse models. Clin Cancer Res 2017;23(15):4335–46. DOI: 10.1158/1078-0432.CCR-16-2955. PMID: 28364014.

9. Porter A.T., McEwan A.J., Powe J.E. et al. Results of a randomized phase-III trial to evaluate the efficacy of strontium-89 adjuvant to local field external beam irradiation in the management of endocrine resistant metastatic prostate cancer. Int J Radiat Oncol 1993;25(5):805–13. PMID: 8478230.

10. Cheetham P.J., Petrylak D.P. Alpha particles as radiopharmaceuticals in the treatment of bone metastases: mechanism of action of radium-223 chloride (Alpharadin) and radiation protection. Oncology 2012;26(4):330–7. PMID: 22655525.

11. Nilsson S. Radium-223 dichloride for the treatment of bone metastatic castrationresistant prostate cancer: an evaluation of its safety. Expert Opin. Drug Saf 2015;14(7):1127–36. DOI: 10.1517/14740338.2015.1045874. PMID: 26022669.

12. Carrasquillo J.A., O’Donoghue J.A., Pandit-Taskar N. et al. Phase I pharmacokinetic and biodistribution study with escalating doses of 223Ra-dichloride in men with castration-resistant metastatic prostate cancer. Eur J Nucl Med Mol Imaging 2013;40(9):1384–93.

13. Parker C., Nilsson S., Heinrich D. et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med 2013;369(3):213–23. DOI: 10.1056/NEJMoa1213755. PMID: 23863050.

14. Hoskin P., Sartor O., O’Sullivan J.M. et al. Efficacy and safety of radium-223 dichloride in patients with castration resistant prostate cancer and symptomatic bone metastases, with or without previous docetaxel use: a prespecified subgroup analysis from the randomised, doubleblind, phase 3 ALSYMPCA trial. Lancet Oncol 2014;15(12):1397–406. DOI: 10.1016/S1470-2045(14)70474-7. PMID: 25439694.

15. Sartor O., Coleman R., Nilsson S. et al. Effect of radium-223 dichloride on symptomatic skeletal events in patients with castration-resistant prostate cancer and bone metastases: results from a phase 3, doubleblind, randomised trial. Lancet Oncol 2014;15(7):738–46. DOI: 10.1016/S1470-2045(14)70183-4. PMID: 24836273.

16. Logue J., Wedel S., Chodacki A. et al. Reasons for patients discontinuing study treatment in the phase 3 ALSYMPCA trial of radium-223 dichloride in castration-resistant prostate cancer with bone metastases. Ann Oncol 2014;25(Suppl 4):abstract 770P.

17. Parker C., Finkelstein S.E., Michalski J.M. et al. Efficacy and safety of radium-223 dichloride in symptomatic castration-resistant prostate cancer patients with or without baseline opioid use from the phase 3 ALSYMPCA Trial. Eur Urol 2016;70(5):875–83. DOI: 10.1016/j.eururo.2016.06.002. PMID: 27344296.

18. Saad F., Carles J., Gillessen S. et al. Radium-223 and concomitant therapies in patients with metastatic castration-resistant prostate cancer: an international, early access, open-label, single-arm phase 3b trial. Lancet Oncol 2016;17(9):1306–16. DOI: 10.1016/S1470-2045(16)30173-5. PMID: 27473888.

19. Xofigo (radium-223 dichloride). Summary of Product Characteristics. Berlin, Germany: Bayer Pharma AG, 2016.

20. Sartor A. Cabazitaxel vs docetaxel in chemotherapy-naive (CN) patients with metastatic castration-resistant prostate cancer (mCRPC): a three-arm phase III study (FIRSTANA). J Clin Oncol 2016. Abstract 5006.

21. Huillard O., Albiges L., Eymard J.C. et al. Efficacy of docetaxel chemotherapy in metastatic prostate cancer (mPC) patients (pts) experiencing early castration resistance (CR). J Clin Oncol 2013;31 [suppl; abstract 5075].

22. Loriot Y., Eymard J.C., Patrikidou A. et al. Prior long response to androgen deprivation predicts response to next-generation androgen receptor axis targeted drugs in castration resistant prostate cancer. Eur J Cancer 2015;51(14):1946–52. DOI: 10.1016/j.ejca.2015.06.128. PMID: 26208462.

23. Dawson N.A., McLeod D.G. The assessment of treatment outcomes in metastatic prostate cancer: Changing endpoints. Eur J Cancer 1997;33(4):560–5. PMID: 9274435.

24. Gillessen S., Omlin A., Attard G. et al. Management of patients with advanced prostate cancer: recommendations of the St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) 2015. Ann Oncol 2015;26(8):1589–604. DOI: 10.1093/annonc/mdv257. PMID: 26041764.

25. Vogelzang N.J., Coleman R.E., Michalski J.M. et al. Hematologic safety of radium-223 dichloride: baseline prognostic factors associated with myelosuppression in the ALSYMPCA trial. Clin Genitourin Cancer 2017;15(1):42–52. DOI: 10.1016/j.clgc.2016.07.027. PMID: 27613490.

26. Zhang W., Wu T.U., Chen Q. et al. Indirect comparison between abiraterone acetate and enzalutamide for the treatment of metastatic castration-resistant prostate cancer: a systematic review. Asian J Androl 2017;19(2):196–202. DOI: 10.4103/1008-682X.178483. PMID: 27212123.

27. Richards J., Lim A.C., Hay C.W. et al. Interactions of abiraterone, eplerenone, and prednisolone with wild-type and mutant androgen receptor: a rationale for increasing abiraterone exposure or combining with MDV3100. Cancer Res 2012;72(9):2176–82. DOI: 10.1158/0008-5472.CAN-11-3980. PMID: 22411952.

28. Sonpavde G., Bhor M., Hennessy D. et al. Sequencing of cabazitaxel and abiraterone acetate after docetaxel in metastatic castration-resistant prostate cancer: treatment patterns and clinical outcomes in multicenter community-based us oncology practices. Clin Genitourin Cancer 2015;13(4):309–18. DOI: 10.1016/j.clgc.2014.12.019. PMID: 25743206.

29. Antonarakis E.S., Tagawa S.T., Galletti G. et al. Randomized, noncomparative, phase II trial of early switch from docetaxel to cabazitaxel or vice versa, with integrated biomarker analysis, in men with chemotherapy-naïve, metastatic, castration-resistant prostate cancer. J Clin Oncol 2017;35(28):3181–8. DOI: 10.1200/JCO.2017.72.4138. PMID: 28632486.

30. Du Y., Carrio I., De Vincentis G. et al. Practical recommendations for radium-223 treatment of metastatic castration-resistant prostate cancer. Eur J Nucl Med Mol Imaging 2017;44(10):1671–8. DOI: 10.1007/s00259-017-3756-7. PMID: 28631036.

31. Sartor O., Vogelzang N.J., Sweeney C. et al. Radium-223 safety, efficacy, and concurrent use with abiraterone or enzalutamide: first U.S. experience from an expanded access program. Oncologist 2018;23(2):193–202. DOI: 10.1634/theoncologist.2017-0413. PMID: 29183960.

32. Logue J., Schostak M., Baldari S. et al. REASSURE observational study of radium-223 (Ra-223): First interim results by prior/concomitant treatment (Tx) in patients (Pts) with metastatic castration-resistant prostate cancer (mCRPC) enrolled in Europe. Eur Urol Suppl 2018;17(2);e1855.

33. de Bono J.S., Oudard S., Ozguroglu M. et al. Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. Lancet 2010;376(9747):1147–54. DOI: 10.1016/S0140-6736(10)61389-X. PMID: 20888992.

34. Crona D.J., Milowsky M.I., Whang Y.E. Androgen receptor targeting drugs in castration-resistant prostate cancer and mechanisms of resistance. Clin Pharmacol Ther 2015;98(6):582–9. DOI: 10.1002/cpt.256. PMID: 26331358.

35. Nakazawa M., Antonarakis E.S., Luo J. Androgen receptor splice variants in the era of enzalutamide and abiraterone. Horm Cancer 2014;5(5):265–73. DOI: 10.1007/s12672-014-0190-1. PMID: 25048254.

36. Antonarakis E.S., Lu C., Wang H. et al. AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer. N Engl J Med 2014;371(11):1028–38.

37. de Bono J.S. Phase III non-inferiority study of cabazitaxel (C) 20 mg/m2 (C20) versus 25 mg/m2 (C25) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) previously treated with docetaxel (D). J Clin Oncol 2016;34:abstract 5008.

38. Al Nakouzi N., Le Moulec S., Albiges L. et al. Cabazitaxel remains active in patients progressing after docetaxel followed by novel androgen receptor pathway targeted therapies. Eur Urol 2015;68(2):228–35. DOI: 10.1016/j.eururo.2014.04.015. PMID: 24837187.

39. Pezaro C.J., Omlin A.G., Altavilla A. et al. Activity of cabazitaxel in castration-resistant prostate cancer progressing after docetaxel and next-generation endocrine agents. Eur Urol 2014;66(3):459–65. DOI: 10.1016/j.eururo.2013.11.044. PMID: 24411987.

40. Sella A., Sella T., Peer A. et al. Activity of cabazitaxel after docetaxel and abiraterone acetate therapy in patients with castration-resistant prostate cancer. Clin Genitourin Cancer 2014;12(6):428–32. DOI: 10.1016/j.clgc.2014.06.007. PMID: 25066221.

41. van Soest R.J., de Morrée E.S., Kweldam C.F. et al. Targeting the androgen receptor confers in vivo cross-resistance between enzalutamide and docetaxel, but not cabazitaxel, in castration-resistant prostate cancer. Eur Urol 2015;67(6):981–85.

42. Delanoy N., Angelergues A., Efstathiou E. et al. Sequencing in metastatic castration-resistant prostate cancer (mCRPC): updated results of the FLAC International Database. J Clin Oncol 2017;35:abstract 267.

43. Chowdhury S., Birtle A.J., Bjartell A. et al. Real-world outcomes in second-line treatment of metastatic castration-resistant prostate cancer (mCRPC): the Prostate Cancer Registry. J Clin Oncol 2017;35:abstract 5038.

44. von Hardenberg J., Schwartz M., Werner T. et al. Оncologic response and hospitalization rate of patients receiving cabazitaxel in the fourth-line and beyond in castration-resistant prostate cancer: analysis of a retrospective cohort and a structured literature review. Urol Int 2017;99(4): 414–21. DOI: 10.1159/000477943. PMID: 28700990.