Journal of Modern OncologyJournal of Modern OncologyСовременная онкология1815-14341815-1442LLC Obyedinennaya Redaktsiya26746ArticlesСтатьиResearch ArticleZnachenie klinicheskikh i molekulyarno-geneticheskikh prediktorov otveta na terapiyu ingibitorami tirozinkinazy v vybore lechebnoy taktiki pri nemelkokletochnom rake legkogoЗначение клинических и молекулярно-генетических предикторов ответа на терапию ингибиторами тирозинкиназы в выборе лечебной тактики при немелкоклеточном раке легкогоSmolinA VСмолинА ВKonevA VКоневА ВSoloveyT GСоловейТ ГNikolaevaS NНиколаеваС НShamanskayaYu EШаманскаяЮ ЕГлавный военный клинический госпиталь им. Н.Н.Бурденко, Москва15122008104NO4 (2008)ТОМ 10, №4 (2008)374209042020Copyright ©; 2008, Consilium MedicumCopyright ©; 2008, ООО "Консилиум Медикум"2008Consilium MedicumООО "Консилиум Медикум"https://creativecommons.org/licenses/by-nc/4.0https://modernonco.orscience.ru/1815-1434/article/view/26746

Рак легкого – ведущая причина онкологической смерти как мужчин, так и женщин. От него умирают больше больных, чем от рака толстой кишки, молочной и предстательной желез, вместе взятых. Рак легкого развивается у каждого 13-го мужчины и у каждой 16-й женщины. Проблема усугубляется тем, что более чем у 55% больных опухоль диагностируется в распространенной (III B, IV) стадии. В 1970–80-е годы велись активные дискуссии о роли химиотерапии в лечении немелкоклеточного рака легкого (НМКРЛ). Точку в этих дискуссиях поставили результаты нескольких метаанализов, проведенных в период с 1993 по 1995 г., продемонстрировавших, что химиотерапия увеличивает медиану выживаемости, одногодичную выживаемость и снижает риск смерти на 24%. Недавно опубликованы данные метаанализа 16 рандомизированных исследований, оценивающих в том числе и новые режимы химиотерапии. Подтверждено преимущество химиотерапии перед симптоматическим лечением ( p ≤0,0001), но вместе с тем не получено данных об отличии в эффективности в зависимости от режима химиотерапии.

немелкоклеточный рак легкогохимиотерапияЭрлотинибRies L.A.G., Melbert D, Krapcho M et al. SEER Cancer Statistics Review, 1975–2005, National Cancer Institute. Bethesda, MD.Grilli R, Oxman A.D, Julian J.A. Chemotherapy for advanced non - small cell lung cancer: how much benefit is enough? J Clin Oncol 1993; 11: 1866.Marino P, Pampallona S, Preatoni A et al. Chemotherapy vs supportive care in advanced non - small - cell lung cancer. Results of a meta - analysis of the literature. Chest 1994; 106: 861.Chemotherapy in non - small cell lung cancer: a meta - analysis using updated data on individual patients from 52 randomised clinical trials. BMJ 1995; 311 (7010): 899–909.Chemotherapy in Addition to Supportive Care Improves Survival in Advanced Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis of Individual Patient Data From 16 Randomized Controlled Trials J Clin Oncol 2008; 26 (28): 4617–25.Sandler A, Gray R, Perry M.C. et al. Paclitaxel - carboplatin alone or with bevacizumab for non - small - cell lung cancer. N Engl J Med 2006; 355: 2542–50.Gatzemeier U, Pluzanska A,Szczesna A et al. Phase III Study of Erlotinib in Combination With Cisplatin and Gemcitabine in Advanced Non-Small-Cell Lung Cancer: The Tarceva Lung Cancer Investigation Trial. J Clin Oncol 2007; 25: 1545–52.Shepherd F.A., Rodrigues Pereira J, Ciuleanu T et al. Erlotinib in previously treated non - small - cell lung cancer. N Engl J Med 2005; 353: 123–32.Herbst R.S., Prager D, Hermann R et al. TRIBUTE: A phase III trial of erlotinib hydrochloride (OSI-774) combined with carboplatin and paclitaxel chemotherapy in advanced non - small - cell lung cancer. J Clin Oncol 2005; 23: 5892-9.Gatzemeier U, Pluzanska A, Szczesna A et al. Phase III study of erlotinib in combination with cisplatin and gemcitabine in advanced non - small - cell lung cancer: The Tarceva Lung Cancer Investigation Trial. J Clin Oncol 2007; 25: 1545–52.Moore M.J., Goldstein D, Hamm J et al. Erlotinib plus gemcitabine compared to gemcitabine alone in patients with advanced pancreatic cancer. A phase III trial of the National Cancer Institute of Canada Clinical Trials Group [NCIC–CTG]. J Clin Oncol 2007; 25: 1960–6.Davies A.M., Ho C, Lara P.N.Jr. et al. Pharmacodynamic separation of epidermal growth factor receptor tyrosine kinase inhibitors and chemotherapy in nonsmallcell lung cancer. Clin Lung Cancer 2006; 7: 385–8.Mahaffey C.M., Davies A.M., Lara P.N. et al. Schedule - dependent apoptosis in Kras mutant non - small - cell lung cancer cell lines treated with docetaxel and erlotinib: rationale for pharmacodynamic separation. Clin Lung Cancer 2007; 8 (9): 548–53.Giovannetti E, Lemos C, Tekle C et al. Molecular Mechanisms Underlying the Synergistic Interaction of Erlotinib, an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor, with the Multitargeted Antifolate Pemetrexed in Non-Small- Cell Lung Cancer Cells. Mol Pharmacol 2008; 73: 1290–300.Jimenez U, Gurpide A, Isla D et al. Erlotinib for first line treatment in unselected patients with advanced or metastatic non - small cell lung carcinoma (NSCLC) J Clin Oncol, 2007 ASCO Annual Meeting Proceedings (Post-Meeting Edition). 2007;25 (18 Suppl.): 7639.Lilenbaum R, Axelrod R, Thomas S et al. Randomized phase II trial of erlotinib or standard chemotherapy in patients with advanced non - small - cell lung cancer and a performance status of 2. J Clin Oncol 2008; 26 (6): 863–9.Imyanitov E.N., Togo A.V., Hanson K.P. Searching for cancer - associated gene polymorphisms: promises and obstacles. Cancer Lett 2004; 204: 3–14. Hamilton M, Wolf J, Rusk J et al. Effects of Smoking on the Pharmacokinetics of Erlotinib. Clin Cancer Res 2006; 12: 2166–71.Toh C.K., Wong E.H., Lim W.T. et al. The impact of smoking status on the behavior and survival outcome of patients with advanced non - small cell lung cancer: A retrospective analysis. Chest 2004; 126: 1750–6.Nordquist L.T., Simon G.R., Cantor A et al. Improved survival in never smokers vs current smokers with primary adenocarcinoma of the lung. Chest 2004; 126: 347–51.Scagliotti G.V., Parikh P, von Pawel J et al. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy - naive patients with advanced - stage non - small - cell lung cancer. J Clin Oncol 2008; 26: 3543–51.Pao W, Miller V, Zakowski M et al. EGF receptor gene mutations are common in lung cancers from "never smokers" and are associated with sensitivity of tumors to gefitinib and erlotinib. Proc Natl Acad Sci USA 2004; 101: 13306–11.Shigematsu H, Lin L, Takahashi T et al. Clinical and biological features associated with epidermal growth factor receptor gene mutations in lung cancers. J Natl Cancer Inst 2005; 97: 339–46.Blackhall F, Ranson M,Thatcher N. Where next for gefitinib in patients with lung cancer? Lancet Oncol 2006; 7: 499–507.Li J, Zhao M, Hidalgo M et al. Differential Metabolism of Gefitinib and Erlotinib by Human Cytochrome P450 Enzymes. Clin Cancer Res 2007; 13 (12).Giovannetti E, Mey V, Nannizzi S et al. Cellular and pharmacogenetics foundation of synergistic interaction of pemetrexed and gemcitabine in human nonsmall cell lung cancer cells. Mol Pharmacol 2005; 68: 110–8.Sandler A, Gray R, Perry M.C. et al. Paclitaxel - carboplatin alone or with bevacizumab for non - small - cell lung cancer. N Engl J Med 2006; 355: 2542–50.Patel J, Hensing T, Villafor V et al. Pemetrexed and carboplatin plus bevacizumab for advanced non - squamous non - small cell lung cancer (NSCLC): Preliminary results. Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings (Post-Meeting Edition). 2007; 25 (18S) Suppl.: 7601.Massarelli E, Andre F, Liu D.D. et al. A retrospective analysis of the outcome of patients who have received two prior chemotherapy regimens including platinum and docetaxel for recurrent non - small - cell lung cancer. Lung Cancer 2003; 39: 55–61.Tsao M.S., Sakurada A, Cutz J.C. et al. Erlotinib in lung cancer: molecular and clinical predictors of outcome. N Engl J Med 2005; 353: 133–44.Shigematsu H, Lin L, Takahashi T et al. Clinical and Biological Features Associated With Epidermal Growth Factor Receptor Gene Mutations in Lung Cancers. JNCI Journal of the National Cancer Institute 2005; 97 (5): 339–46.Lecia V Sequist, Renato G et al. First - Line Gefitinib in Patients With Advanced Non-Small-Cell Lung Cancer Harboring Somatic EGFR Mutations. J Clin Oncol 2008; 26 (15): 2442–9.Wheatley-Price P, Shepherd F.A. Epidermal growth factor receptor inhibitors in the treatment lung cancer: Reality and hopes. Curr Opin Oncol 2008; 20:162–75.