Journal of Modern OncologyJournal of Modern OncologyСовременная онкология1815-14341815-1442LLC Obyedinennaya Redaktsiya26926ArticlesСтатьиResearch ArticleSelection of the anti-angiogenesis therapy for the first-line chemotherapy in advanced ovarian cancerВыбор антиангиогенной терапии для лечения первой линии распространенного рака яичниковKhokhlovaS VХохловаСветлана Викторовна

канд. мед. наук, ст. науч. сотр. отд-ния химиотерапии

ФГБУ Российский онкологический научный центр им. Н.Н.Блохина РАМН15032014161VOL 16, NO1 (2014)ТОМ 16, №1 (2014)131709042020Copyright ©; 2014, Consilium MedicumCopyright ©; 2014, ООО "Консилиум Медикум"2014Consilium MedicumООО "Консилиум Медикум"https://creativecommons.org/licenses/by-nc/4.0https://modernonco.orscience.ru/1815-1434/article/view/26926

Development of first-line cytostatic therapy in ovarian cancer is slow, and as a result, the main research aim today is to study the biology of the disease. Angiogenesis is one of the main factors of the tumor microenvironment, resulting in growth and metastasis. As a result have been investigated the drugs inhibiting angiogenesis. The first drug being studied in phase III trial of the randomized studies was bevacizumab, which demonstrated the significant increase in both progression-free survival and survival in the high risk group. Other antiangiogenics such as pazopanib, nintenanib, also demonstrated high efficacy in patients with ovarian cancer.

Развитие цитостатической терапии в 1-й линии лечения рака яичников происходит медленно, и, как следствие, в последние годы основной поиск исследований направлен на изучение биологии данного заболевания. Ангиогенез является одним из основных факторов микроокружения опухоли, приводящим к росту и метастазированию заболевания. В связи с этим начали появляться препараты, ингибирующие ангиогенез. Одним из первых препаратов, изучаемых в III фазе рандомизированных исследований, был бевацизумаб, который продемонстрировал достоверное увеличение как выживаемости без прогрессирования, так и продолжительности жизни в группе высокого риска больных. Другие антиангиогенные препараты, такие как пазопаниб, нинтенаниб, также демонстрируют высокую эффективность у пациенток с раком яичников.

VEGFVEGFbevacizumabovarian cancerбевацизумабрак яичниковSiegel R, Naishadham D, Jemal A. Cancer statistics 2013. CA Cancer J Clin 2013; 63: 11-30.Bookman M. Trials with impact on clinical management: first line. Int J Gyn Cancer 2009; 19 (Suppl. 2): s55-62.Chien J, Kuang R, Landen C, Shridhar V. Platinum - sensitive recurrence in ovarian cancer: the role of tumor microenvironment. Front Oncol 2013; 3: 251.Galluzzi L, Senovilla I, Vitale J et al. Molecular mechanisms of cisplatin resistance. Oncogene 2012; 31: 1869-83.Said N, Socha M.J, Olearczyk J.J et al. Normalization of the ovarian cancer microenvironment by SPARC. Mol Cancer Res 2007; 5: 1015-30.Fukumura D, Jain R. Tumor microvasculature and microenvironment: targets for anti - angiogenesis and normalization. Microvasc Res 2007; 74: 72-84.Kassis J, Klominek J, Kohn E. Tumor microenvironment: what can effusions teach us? Diagn Cytopathol 2005; 33: 316-9.Leinster D.A, Kulbe H, Everitt G et al. The peritoneal tumour microenvironment of high - grade serous ovarian cancer. J Pathol 2012; 227: 136-45.Eskander R.N, Randall L.M. Bevacizumab in the treatment of ovarian cancer. Biologics 2011; 5: 1-5.Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med 1971; 285: 1182-6.Ferrara N. Molecular and biological properties of vascular endothelial growth factor. J Mol Med (Berl) 1999; 77: 527-43.Stewart M.W, Grippon S, Kirkpatrick P. Aflibercept Nat Rev Drug Dis 2012; 11: 269-70.Yancopoulos G.D, Davis S, Gale N.W et al. Vascular - specific growth factors and blood vessel formation. Nature 2000; 407: 242-8.Rusnati M, Presta M. Fibroblast growth factors/fibroblast growth factor receptors as targets for the development of anti - angiogenesis strategies. Curr Pharm Des 2007; 13: 2025-44.Burger R.A, Sill M.W, Monk B.J et al. Phase II trial of bevacizumab in persistent or recurrent epithelial ovarian cancer or primary peritoneal cancer: a Gynecologic Oncology Group Study. J Clin Oncol 2007; 25: 5165-71.Cannistra S.A, Matulonis U.A, Penson R.T et al. Phase II study of bevacizumab in patients with platinum - resistant ovarian cancer or peritoneal serous cancer. J Clin Oncol 2007; 25: 5180-6.Garcia A, Hirte H, Fleming G et al. Phase II clinical trial of bevacizumab and low - dose metronomic oral cyclophosphamide in recurrent ovari an cancer: a trial of the California, Chicago, and Princess Margaret Hospital phase II consortia. J Clin Oncol 2008; 26: 76-82.Tillmanns L.M, Schwartzberg L.S, Walker M.S, Stepanski E.J. A phase II study of bevacizumab with nab - paclitaxel in patients with recurrent, platinum - resistant primary epithelial ovarian or primary peritoneal carcinoma. J Clin Oncol 2010; 28.Gonzalez-Martin A, Gladieff L, Tholander B et al. Efficacy and safety results from OCTAVIA, a single - arm phase II study evaluating front - line bevacizumab, carboplatin and weekly paclitaxel for ovarian cancer. Eur J Cancer 2013; 49: 3831-8.Matulonis U.A, Berlin S, Ivy P et al. Cediranib, an oral inhibitor of vascular endothelial growth factor receptor kinases, is an active drug in recurrent epithelial ovarian, fallopian tube, and peritoneal cancer. J Clin Oncol 2009; 27: 5601-6.Karlan B.Y, Oza A.M, Richardson G.E et al. Randomized, double - blind, placebo - controlled phase II study of AMG 386 combined with weekly paclitaxel in patients with recurrent ovarian cancer. J Clin Oncol 2012; 30: 362-71.Gotlieb W.H, Amant F, Advani S et al. Intravenous aflibercept for treatment of recurrent symptomatic malignant ascites in patients with advanced ovarian cancer: a phase II, randomised, double - blind, placebo - controlled study. Lancet Oncol 2012; 13: 154-62.Colombo N, Mangili G, Mammoliti S et al. A phase II study of aflibercept in patients with advanced epithelial ovarian cancer and symptomatic malignant ascites. Gyn Oncol 2012; 125: 42-7.Friedlander M, Hancock K.C, Rischin D et al. A phase II, open - label study evaluating pazopanib in patients with recurrent ovarian cancer. Gyn Oncol 2010; 119: 32-7.Ledermann J.A, Hackshaw A, Kaye S et al. Randomized phase II placebo - controlled trial of maintenance therapy using the oral triple angiokinase inhibitor BIBF 1120 after chemotherapy for relapsed ovarian cancer. J Clin Oncol 2011; 29: 3798-804.Burger R.A, Brady M.F, Bookman M.A et al. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med 2011; 365: 2473-83.Burger R, Bookman M, Monk B et al. Prospective investigation of risk factors for gastrointestinal adverse events in a phase III randomized trial of bevacizumab in first - line therapy of advanced epithelial ovarian cancer, primary peritoneal cancer or fallopian tube cancer: a Gynecologic Oncology Group study. Gyn Oncol 2011; 120: s5.Perren T.J, Swart A.M, Pfisterer J et al. A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med 2011; 365: 2484-96.Oza A.M, Swart A.M, Schröder W et al. ICON-7: final overall survival results in the GCIG phase III randomized trial of bevacizumab in women with newly diagnosed ovarian cancer. Eur J Cancer 2013; 49 (Suppl. 3): LBA 6.Andreas A.F, du Bois A, Kim J.W et al. Randomized, double - blind, phase III trial of pazopanib vs placebo in women who have not progressed after first - line chemotherapy for advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer (AEOC): results of an international Intergroup trial (AGO-OVAR-16). J Clin Oncol 2013; 31. Abstr. LBA 5503.du Bois A, Kristensen G, Ray-Coquard I et al. AGO-OVAR 12: a randomized placebo - controlled GCIG/ENGOT-intergroup phase III trial of standard frontline chemotherapy ± nintedanib for advanced ovarian cancer. Int J Gyn Cancer 2013; 23 (Suppl. 1): LBA 1.