medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/2079-701X-2018-19-17-21medsovet-2741Research ArticleТАРГЕТНАЯ ТЕРАПИЯ ОПУХОЛЕЙTarget therapy of tumorsСовременные аспекты антиангиогенной терапии при раке яичниковModern aspects of antiangiogenic therapy in ovarian cancerРумянцевА. А.RumyantsevA. A.

сотрудник отделения клинической фармакологии и химиотерапии

ПокатаевИ. А.PokataevI. A.

к.м.н., старший научный сотрудник отделения клинической фармакологии и химиотерапии ФГБУ «Национальный медицинский исследовательский центр онкологии

ТюляндинС. А.TyulyandinS. A.

д.м.н., профессор, заведующий отделением клинической фармакологии и химиотерапии

ФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина» Минздрава России, МоскваРоссияBlokhin National Medical Research Cancer Centre, Federal State Budgetary Institution of the Ministry of Health of Russia, MoscowRussian Federation2018111120180191721Copyright © Румянцев А.А., Покатаев И.А., Тюляндин С.А., 20182018Румянцев А.А., Покатаев И.А., Тюляндин С.А.Rumyantsev A.A., Pokataev I.A., Tyulyandin S.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-sovet.pro/jour/article/view/2741

Процессы неоангиогенеза критически важны для роста и распространения злокачественных опухолей. Антиангиогенная терапия прочно вошла в стандарты лечения диссеминированного рака яичников (РЯ). Результаты многочисленных исследований продемонстрировали ее эффективность на различных этапах терапии этого заболевания, наиболее изученным при РЯ антиангиогенным препаратом является бевацизумаб. В этой статье представлены обзор и анализ наиболее значимых исследований эффективности антиангиогенной терапии при РЯ, описаны различные аспекты ее применения при этом заболевании.

The process of angiogenesis is essential for the growth and spread of malignant tumours. Antiangiogenic therapy is deeply embedded in the standard treatment of disseminated ovarian cancer (OC). The numerous studies have demonstrated its efficacy in various stages of the therapy of this disease; bevacizumab is the best-investigated anti-angiogenic drug for OC. This article presents a review and analysis of the most significant studies of the efficacy of anti-angiogenic therapy in ovarian cancer, and describes various aspects of its use in this disease.

рак яичниковантиангиогенная терапиябевацизумабovarian cancerantiangiogenic therapybevacizumabReferencesЗлокачественные новообразования в России в 2017 году (Заболеваемость и смертность). Под ред. Каприна А.Д., Старинского В.В., Петровой Г.В. М.: МНИОИ им. П.А. Герцена – филиал ФГБУ «НМИЦ радиологии» Минздрава России, 2018. 250 с.Malignant neoplasms in Russia, 2017 (morbidity and mortality). Under the editorship of Kaprina AD, Starinsky VV, Petrova GV. M.: Hertsen Moscow Oncology Research Center - branch of FSBI NMRRC of the Ministry of Health of Russia, 2018. 250 p.Noone AM, Howlader N, Krapcho M, Miller D, Brest A, Yu M et al. SEER Cancer Statistics Review, 1975-2015, National Cancer Institute. Bethesda, MD, https://seer.cancer.gov/ csr/1975_2015/, based on November 2017 SEER data submission, posted to the SEER web site, April 2018.Noone AM, Howlader N, Krapcho M, Miller D, Brest A, Yu M et al. SEER Cancer Statistics Review, 1975-2015, National Cancer Institute. Bethesda, MD, https://seer.cancer.gov/ csr/1975_2015/, based on November 2017 SEER data submission, posted to the SEER web site, April 2018.Folkman J. Tumor angiogenesis: therapeutic implications. The New England Journal of Medicine, 1971 Nov 18, 285(21): 1182-1186.Folkman J. Tumor angiogenesis: therapeutic implications. The New England Journal of Medicine, 1971 Nov 18, 285(21): 1182-1186.Carmeliet P, Jain RK. Angiogenesis in cancer and other diseases. Nature, 2000 Sept, 407(6801): 249-257.Carmeliet P, Jain RK. Angiogenesis in cancer and other diseases. Nature, 2000 Sept, 407(6801): 249-257.Avril S, Dincer Y, Malinowsky K, Wolff C, Gündisch S, Hapfelmeier A et al. Increased PDGFR-beta and VEGFR-2 protein levels are associated with resistance to platinum-based chemotherapy and adverse outcome of ovarian cancer patients. Oncotarget, 2017 Jun 8, 8(58): 97851-97861.Avril S, Dincer Y, Malinowsky K, Wolff C, Gündisch S, Hapfelmeier A et al. Increased PDGFR-beta and VEGFR-2 protein levels are associated with resistance to platinum-based chemotherapy and adverse outcome of ovarian cancer patients. Oncotarget, 2017 Jun 8, 8(58): 97851-97861.NCCN Clinical Practice Guidelines. Ovarian cancer. Version 1, 2018.NCCN Clinical Practice Guidelines. Ovarian cancer. Version 1, 2018.Тюляндин С.А., Коломиец Л.А., Морхов К.Ю., Нечушкина В.М., Покатаев И.А., Тюляндина А.С. и соавт. Практические рекомендации по лекарственному лечению рака яичников, первичного рака брюшины и рака маточных труб. Злокачественные опухоли: Практические рекомендации RUSSCO #3s2, 2017, 7: 135–145.Tyulyandin SA, Kolomiets LA, Morkhov KYu, Nechushkina VM, Pokatayev IA, Tyulyandina AS, et al. Practical guidelines for the drug treatment of ovarian cancer, primary peritoneal cancer and tubal cancer. Zlokachestvennye Opukholi: Prakticheskie Rekomendacii RUSSCO # 3s2, 2017, 7: 135–145.Bookman MA, Brady MF, McGuire WP, Harper PG, Alberts DS, Friedlander M et al. Evaluation of New Platinum-Based Treatment Regimens in Advanced-Stage Ovarian Cancer: A Phase III Trial of the Gynecologic Cancer InterGroup. J Clin Oncol, March 20, 2009, 27(9): 1419-1425.Bookman MA, Brady MF, McGuire WP, Harper PG, Alberts DS, Friedlander M et al. Evaluation of New Platinum-Based Treatment Regimens in Advanced-Stage Ovarian Cancer: A Phase III Trial of the Gynecologic Cancer InterGroup. J Clin Oncol, March 20, 2009, 27(9): 1419-1425.Burger RA, Brady MF, Bookman MA, Fleming GF, Monk BJ, Huang H et al. Incorporation of Bevacizumab in the Primary Treatment of Ovarian Cancer. N Engl J Med, 2011 Dec 29, 365(26): 2473-2483.Burger RA, Brady MF, Bookman MA, Fleming GF, Monk BJ, Huang H et al. Incorporation of Bevacizumab in the Primary Treatment of Ovarian Cancer. N Engl J Med, 2011 Dec 29, 365(26): 2473-2483.Oza AM, Selle F, Davidenko I, Korach J, Mendiola C, Pautier P et al. Efficacy and Safety of Bevacizumab-Containing Therapy in Newly Diagnosed Ovarian Cancer: ROSiA Single-Arm Phase 3B Study. Int J Gynecol Cancer, 2017 Jan, 27(1): 50-58.Oza AM, Selle F, Davidenko I, Korach J, Mendiola C, Pautier P et al. Efficacy and Safety of Bevacizumab-Containing Therapy in Newly Diagnosed Ovarian Cancer: ROSiA Single-Arm Phase 3B Study. Int J Gynecol Cancer, 2017 Jan, 27(1): 50-58.Perren TJ, Swart AM, Pfisterer J, Ledermann JA, Pujade-Lauraine E, Kristensen G et al. A Phase 3 Trial of Bevacizumab in Ovarian Cancer. N Engl J Med, 2011 Dec 29, 365(26): 2484-2496.Perren TJ, Swart AM, Pfisterer J, Ledermann JA, Pujade-Lauraine E, Kristensen G et al. A Phase 3 Trial of Bevacizumab in Ovarian Cancer. N Engl J Med, 2011 Dec 29, 365(26): 2484-2496.Du Bois A, Floquet A, Kim J-W, Rau J, del Campo JM, Friedlander M et al. Incorporation of Pazopanib in Maintenance Therapy of Ovarian Cancer. J Clin Oncol, 2014 Oct 20, 32(30): 3374-3382.Du Bois A, Floquet A, Kim J-W, Rau J, del Campo JM, Friedlander M et al. Incorporation of Pazopanib in Maintenance Therapy of Ovarian Cancer. J Clin Oncol, 2014 Oct 20, 32(30): 3374-3382.Kim J-W, Mahner S, Wu L-Y, Shoji T, Kim B-G, Zhu J-Q et al. Pazopanib Maintenance Therapy in East Asian Women With Advanced Epithelial Ovarian Cancer: Results From AGO-OVAR16 and an East Asian Study. Int J Gynecol Cancer, 2018 Jan, 28(1): 2-10.Kim J-W, Mahner S, Wu L-Y, Shoji T, Kim B-G, Zhu J-Q et al. Pazopanib Maintenance Therapy in East Asian Women With Advanced Epithelial Ovarian Cancer: Results From AGO-OVAR16 and an East Asian Study. Int J Gynecol Cancer, 2018 Jan, 28(1): 2-10.Hainsworth JD, Thompson DS, Bismayer JA, Gian VG, Merritt WM, Whorf RC et al. Paclitaxel/ carboplatin with or without sorafenib in the first-line treatment of patients with stage III/IV epithelial ovarian cancer: a randomized phase II study of the Sarah Cannon Research Institute. Cancer Med, 2015 May, 4(5): 673-681.Hainsworth JD, Thompson DS, Bismayer JA, Gian VG, Merritt WM, Whorf RC et al. Paclitaxel/ carboplatin with or without sorafenib in the first-line treatment of patients with stage III/IV epithelial ovarian cancer: a randomized phase II study of the Sarah Cannon Research Institute. Cancer Med, 2015 May, 4(5): 673-681.Du Bois A, Kristensen G, Ray-Coquard I, Reuss A, Pignata S, Colombo N et al. Standard firstline chemotherapy with or without nintedanib for advanced ovarian cancer (AGO-OVAR 12): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet Oncol, 2016 Jan, 17(1): 78-89.Du Bois A, Kristensen G, Ray-Coquard I, Reuss A, Pignata S, Colombo N et al. Standard firstline chemotherapy with or without nintedanib for advanced ovarian cancer (AGO-OVAR 12): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet Oncol, 2016 Jan, 17(1): 78-89.Kommoss S, Winterhoff B, Oberg AL, Konecny GE, Wang C, Riska SM et al. Bevacizumab May Differentially Improve Ovarian Cancer Outcome in Patients with Proliferative and Mesenchymal Molecular Subtypes. Clin Cancer Res, 2017 Jul 15, 23(14): 3794-3801.Kommoss S, Winterhoff B, Oberg AL, Konecny GE, Wang C, Riska SM et al. Bevacizumab May Differentially Improve Ovarian Cancer Outcome in Patients with Proliferative and Mesenchymal Molecular Subtypes. Clin Cancer Res, 2017 Jul 15, 23(14): 3794-3801.Pujade-Lauraine E, Hilpert F, Weber B, Reuss A, Poveda A, Kristensen G et al. Bevacizumab Combined With Chemotherapy for PlatinumResistant Recurrent Ovarian Cancer: The AURELIA Open-Label Randomized Phase III Trial. J Clin Oncol, 2014 May, 32(13): 1302-1308.Pujade-Lauraine E, Hilpert F, Weber B, Reuss A, Poveda A, Kristensen G et al. Bevacizumab Combined With Chemotherapy for PlatinumResistant Recurrent Ovarian Cancer: The AURELIA Open-Label Randomized Phase III Trial. J Clin Oncol, 2014 May, 32(13): 1302-1308.Aghajanian C, Blank SV, Goff BA, Judson PL, Teneriello MG, Husain A et al. OCEANS: A Randomized, Double-Blind, Placebo-Controlled Phase III Trial of Chemotherapy With or Without Bevacizumab in Patients With Platinum-Sensitive Recurrent Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancer. J Clin Oncol, 2012 Jun 10, 30(17): 2039-2045.Aghajanian C, Blank SV, Goff BA, Judson PL, Teneriello MG, Husain A et al. OCEANS: A Randomized, Double-Blind, Placebo-Controlled Phase III Trial of Chemotherapy With or Without Bevacizumab in Patients With Platinum-Sensitive Recurrent Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancer. J Clin Oncol, 2012 Jun 10, 30(17): 2039-2045.Aghajanian C, Goff B, Nycum LR, Wang YV, Husain A, Blank SV. Final overall survival and safety analysis of OCEANS, a phase 3 trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent ovarian cancer. Gynecol Oncol, 2015 Oct, 139(1): 10-16.Aghajanian C, Goff B, Nycum LR, Wang YV, Husain A, Blank SV. Final overall survival and safety analysis of OCEANS, a phase 3 trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent ovarian cancer. Gynecol Oncol, 2015 Oct, 139(1): 10-16.Coleman RL, Brady MF, Herzog TJ, Sabbatini P, Armstrong DK, Walker JL et al. Bevacizumab and paclitaxel–carboplatin chemotherapy and secondary cytoreduction in recurrent, platinumsensitive ovarian cancer (NRG Oncology/ Gynecologic Oncology Group study GOG-0213): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol, 2017 Jun, 18(6): 779-791.Coleman RL, Brady MF, Herzog TJ, Sabbatini P, Armstrong DK, Walker JL et al. Bevacizumab and paclitaxel–carboplatin chemotherapy and secondary cytoreduction in recurrent, platinumsensitive ovarian cancer (NRG Oncology/ Gynecologic Oncology Group study GOG-0213): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol, 2017 Jun, 18(6): 779-791.Bamias A, Gibbs E, Khoon Lee C, Davies L, Dimopoulos M, Zagouri F et al. Bevacizumab with or after chemotherapy for platinum-resistant recurrent ovarian cancer: exploratory analyses of the AURELIA trial. Ann Oncol, 2017 Aug 1, 28(8): 1842–1848.Bamias A, Gibbs E, Khoon Lee C, Davies L, Dimopoulos M, Zagouri F et al. Bevacizumab with or after chemotherapy for platinum-resistant recurrent ovarian cancer: exploratory analyses of the AURELIA trial. Ann Oncol, 2017 Aug 1, 28(8): 1842–1848.Oza AM, Cook AD, Pfisterer J, Embleton A, Ledermann JA, Pujade-Lauraine E et al. Standard chemotherapy with or without bevacizumab for women with newly diagnosed ovarian cancer (ICON7): overall survival results of a phase 3 randomised trial. Lancet Oncol, 2015 Aug, 16(8): 928-936.Oza AM, Cook AD, Pfisterer J, Embleton A, Ledermann JA, Pujade-Lauraine E et al. Standard chemotherapy with or without bevacizumab for women with newly diagnosed ovarian cancer (ICON7): overall survival results of a phase 3 randomised trial. Lancet Oncol, 2015 Aug, 16(8): 928-936.Pignata S, Lorusso D, Gallo C. Chemotherapy plus or minus bevacizumab for platinum-sensitive ovarian cancer patients recurring after a bevacizumab containing first line treatment: The randomized phase 3 trial MITO16BMaNGO OV2B-ENGOT OV17. J Clin Oncol, 2018, 36(suppl; abstr 5506).Pignata S, Lorusso D, Gallo C. Chemotherapy plus or minus bevacizumab for platinum-sensitive ovarian cancer patients recurring after a bevacizumab containing first line treatment: The randomized phase 3 trial MITO16BMaNGO OV2B-ENGOT OV17. J Clin Oncol, 2018, 36(suppl; abstr 5506).Chekerov R, Hilpert F, Mahner S, El-Balat A, Harter P, De Gregorio N et al. Sorafenib plus topotecan versus placebo plus topotecan for platinum-resistant ovarian cancer (TRIAS): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Oncol, 2018 Sep, 19(9): 1247-1258.Chekerov R, Hilpert F, Mahner S, El-Balat A, Harter P, De Gregorio N et al. Sorafenib plus topotecan versus placebo plus topotecan for platinum-resistant ovarian cancer (TRIAS): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Oncol, 2018 Sep, 19(9): 1247-1258.Pignata S, Lorusso D, Scambia G, Sambataro D, Tamberi S, Cinieri S et al. Pazopanib plus weekly paclitaxel versus weekly paclitaxel alone for platinum-resistant or platinum-refractory advanced ovarian cancer (MITO 11): a randomised, open-label, phase 2 trial. Lancet Oncol, 2015 May, 16(5): 561-568.Pignata S, Lorusso D, Scambia G, Sambataro D, Tamberi S, Cinieri S et al. Pazopanib plus weekly paclitaxel versus weekly paclitaxel alone for platinum-resistant or platinum-refractory advanced ovarian cancer (MITO 11): a randomised, open-label, phase 2 trial. Lancet Oncol, 2015 May, 16(5): 561-568.Richardson DL, Sill MW, Coleman RL, Sood AK, Pearl ML, Kehoe SM et al. Paclitaxel With and Without Pazopanib for Persistent or Recurrent Ovarian Cancer: A Randomized Clinical Trial. JAMA Oncol, 2018 Feb 1, 4(2): 196.Richardson DL, Sill MW, Coleman RL, Sood AK, Pearl ML, Kehoe SM et al. Paclitaxel With and Without Pazopanib for Persistent or Recurrent Ovarian Cancer: A Randomized Clinical Trial. JAMA Oncol, 2018 Feb 1, 4(2): 196.Lan C-Y, Wang Y, Xiong Y, Li J-D, Shen J-X, Li Y-F et al. Apatinib combined with oral etoposide in patients with platinum-resistant or platinumrefractory ovarian cancer (AEROC): a phase 2, single-arm, prospective study. Lancet Oncol, 2018 Sep, 19(9): 1239-1246.Lan C-Y, Wang Y, Xiong Y, Li J-D, Shen J-X, Li Y-F et al. Apatinib combined with oral etoposide in patients with platinum-resistant or platinumrefractory ovarian cancer (AEROC): a phase 2, single-arm, prospective study. Lancet Oncol, 2018 Sep, 19(9): 1239-1246.Государственный реестр лекарственных средств. Государственный реестр предельных отпускных цен. Бевацизумаб (09.11.2012 (274/20-12). Последний доступ: 13.10.2018.State register of medicinal products. State register of maximum selling prices. Bevacizumab (09/11/2012 (274 / 20-12). Last Access: 10/13/2018.

The authors declare that there are no conflicts of interest present.