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Опыт применения комбинации эверолимуса с аналогами соматостатина пролонгированного действия при высокодифференцированных (G1–G2) нейроэндокринных опухолях
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Markovich A.A., Kuzminov A.E., Orel N.F. et al. Experience of use of everolimus and long-acting somatostatin analogues combination in highly differentiated (G1–G2) neuroendocrine tumors. Journal of Modern Oncology. 2015; 17 (3): 92–95.
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Ключевые слова: нейроэндокринные опухоли, эверолимус.
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Everolimus is the targeted drug approved for the treatment of neuroendocrine tumors (NET). Efficacy of everolimus in combination with octreotide-depo has been shown in Radiant-2 randomized trial in patients with well-differentiated NET in different locations. Everolimus as monotherapy versus placebo was studied in patients with pancreatic NET in the framework of Radiant-3 randomized trial, where the statistically significant advantage of everolimus was proved. The article presents the experience of targeted therapy in 33 patients with highly-differentiated NET in different locations, and some aspects of everolimus use are analyzed. Efficacy, toxicity and long-term results of therapy are evaluated. Everolimus has demonstrated its efficacy in the unfavorable group of patients, most of whom were heavily pretreated with multiple courses of chemo- and biotherapy. Tumor growth control was 79%. Toxic complications were adequately managed by dose reduction of the drug without compromising its effectiveness. Moreover, clinically significant toxicity appeared an efficacy predictor as complicated cases showed twofold increase in median disease-free survival. Preliminary data suggest that therapy with everolimus is preferable at the first stages of treatment of NET.
Key words: neuroendocrine tumors, everolimus.
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1. Yao JC, Phan AT, Chang DZ et al. Efficacy of RAD001 (everolimus) and octreotide LAR in advanced low- to intermediate-grade neuroendocrine tumors: results of a phase II study. J Clin Oncol 2008; 26 (26): 4311–8.
2. Yao JC, Lombard-Bohas C, Baudin E et al. Daily oral everolimus activity in patients with metastatic pancreatic neuroendocrine tumours after failure of cytotoxic chemotherapy: a phase II trial. J Clin Oncol 2010; 28: 69–76.
3. Duran I, Kortmansky J, Singh D et al. A phase II clinical and pharmacodynamic study of temsirolimus in advanced neuroendocrine carcinomas. Brit J Cancer 2006; 95: 1148–54.
4. Susini C, Buscail L. Rationale for the use of somatostatin analogs as antitumor agents. Ann Oncol 2006; 17: 1733–42.
5. Pavel M, Hainsworth JD, Baudin E et al. A randomized, double-blind, placebo-controlled, multicenter phase III trial of everolimus + octreotide LAR vs. placebo + octreotide lar in patients with advanced neuroendocrine tumors – NET (RADIANT-2). Abstr. LBA8. 35th ESMO Congress. Milan, 8–12 Oct 2010.
6. Yao JC, Shah MH, Ito T et al. A randomized, double-blind, placebo-controlled, multicenter phase III trial of everolimus in patients with advanced pancreatic neuroendocrine tumors – PNET (RADIANT-3). Abstr. LBA9 35th ESMO Congress. Milan, 8–12 Oct 2010.
1 ФГБУ Российский онкологический научный центр им. Н.Н.Блохина Минздрава России. 115478, Россия, Москва, Каширское ш., д. 23;
2 ГБОУ ВПО Московский государственный медико-стоматологический университет им. А.И.Евдокимова Минздрава России. 127473, Россия, Москва, ул. Делегатская, д. 20, стр. 1
*a-markovich@yandex.ru
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A.A.Markovich*1, A.E.Kuzminov1, N.F.Orel1, A.S.Odintsova1, G.S.Emelyanova2, V.A.Gorbunova1
1 N.N.Blokhin Russian Cancer Research Center of the Ministry of Health of the Russian Federation. 115478, Russian Federation, Moscow, Kashirskoe sh., d. 23;
2 A.I.Evdokimov Moscow State Medical and Dental University of the Ministry of Health of the Russian Federation. 127473, Russian Federation, Moscow, ul. Delegatskaia, d. 20, str. 1
*a-markovich@yandex.ru