Journal of Modern OncologyJournal of Modern OncologyСовременная онкология1815-14341815-1442LLC Obyedinennaya Redaktsiya26881ArticlesСтатьиResearch ArticleEfficacy and safety of pemetrexed maintenance therapy in advanced non-small-cell lung cancer: a review of phase III studiesЭффективность и профиль безопасности поддерживающей терапии пеметрекседом при немелкоклеточном раке легкого поздних стадий: обзор исследований III фазыKitO IКитОлег Иванович

д-р мед. наук, проф., дир. РНИОИ

VladimirovaL YuВладимироваЛюбовь Юрьевна

д-р мед. наук, проф., руководитель отд-ния химиогормонотерапии РНИОИ

SholokhovaE AШолоховаЕвгения Александровна

мед. советник

Sholokhova_Evgeniya@lilly.comРостовский научно-исследовательский онкологический институтЭли Лилли Восток С.А., Российское представительство, Москва15032013151NO1 (2013)ТОМ 15, №1 (2013)273109042020Copyright ©; 2013, Consilium MedicumCopyright ©; 2013, ООО "Консилиум Медикум"2013Consilium MedicumООО "Консилиум Медикум"https://creativecommons.org/licenses/by-nc/4.0https://modernonco.orscience.ru/1815-1434/article/view/26881

In Russia, over 57,000 new cases of malignant tumors of the trachea, bronchi, and lung were diagnosed in 2009, accounting for 19,8% of all cancers in men and 3,9% of all cancers in women. For most patients in Russia, these cancers are detected at a late stage (stage III – 32,4% and stage IV – 36,0%). Administration of maintenance therapy is one strategy to prolong response or the length of stable disease, resulting in improved survival for patients whose disease has not progressed after first-line induction therapy. This review will summarize the results of phase 3 studies of pemetrexed as maintenance therapy in advanced non-small cell lung cancer.

В России в 2009 г. зарегистрировано более 57 тыс. новых случаев злокачественных новообразований трахеи, бронхов и легкого, что составляет 19,8% всех случаев рака у мужчин и 3,9% у женщин. В большинстве случаев эти формы рака выявляются уже на поздней стадии: III стадия – у 32,4%, IV стадия – у 36,0% пациентов. Одним из подходов к увеличению продолжительности периода ремиссии или стабилизации заболевания и, как следствие, увеличению выживаемости является назначение поддерживающей терапии у пациентов без прогрессирования заболевания после 1-й линии индукционной химиотерапии. В данном обзоре обобщены результаты исследований III фазы по оценке пеметрекседа в составе поддерживающей терапии при немелкоклеточном раке легкого поздних стадий.

non-small cell lung cancernonsquamous non-small cell lung cancermaintenance therapypemetrexedнемелкоклеточный рак легкогонеплоскоклеточный немелкоклеточный рак легкогоподдерживающая терапияпеметрекседGlobocan 2008 Cancer Fact Sheet. http://globocan.iarc.fr/factsheets/cancers/lung.aspDavydov M.I. Cancer statistics in Russia and CIS in 2009. J N.N.Blokhin Russian Cancer Research Center RAMS 2011; 22 (3) (85 Suppl. 1).D’Addario G, Früh M, Reck M et al. Metastatic non - small cell lung cancer. ESMO clinical practice guidelines for diagnosis, treatment and follow - up. Ann Oncol 2010; 21 (Suppl. 5): v116–9.Azzoli C.G., Temin S, Aliff T et al. 2011 focused update of 2009 American Society of Clinical Oncology clinical practice guideline update on chemotherapy for stage IV non - small cell lung cancer. J Clin Oncol 2011; 29 (28): 3825–31.Gridelli C, Maione P, Rossi A et al. Potential treatment options after first - line chemotherapy for advanced NSCLC: maintenance treatment or early second - line? Oncol 2009; 14 (2): 137–47.Grossi F, Aita M, Follador A et al. Sequential, alternating, and maintenance/consolidation chemotherapy in advanced non - small cell lung cancer: a review of the literature. Oncol 2007; 12 (4): 451–64.Stinchcombe T.E., Socinski M.A. Treatment paradigms for advanced stage non - small cell lung cancer in the era of multiple lines of therapy. J Thorac Oncol 2009; 4 (2): 243–50.Smith I.E., O’Brien M.E., Talbot D.C. et al. Duration of chemotherapy in advanced non - small cell lung cancer: a randomized trial of three vs six courses of mitomycin, vinblastine, and cisplatin. J Clin Oncol 2001; 19 (5): 1336–43.Socinski M.A., Schell M.J., Peterman A et al. Phase III trial comparing a defined duration of therapy vs continuous therapy followed by second - line therapy in advanced - stage IIIB/IV non - small cell lung cancer. J Clin Oncol 2002; 20 (5): 1335–43.Belani C.P., Barstis J, Perry M.C. et al. Multicenter, randomized trial for stage IIIB or IV non - small cell lung cancer using weekly paclitaxel and carboplatin followed by maintenance weekly paclitaxel or observation. J Clin Oncol 2003; 21 (15): 2933–9.Westeel V, Quoix E, Moro-Sibilot D et al. Randomized study of maintenance vinorelbine in responders with advanced non - small cell lung cancer. J National Cancer Institute 2005; 97 (7): 499–506.Brodowicz T, Krzakowski M, Zwitter M et al. Cisplatin and gemcitabine first - line chemotherapy followed by maintenance gemcitabine or best supportive care in advanced non - small cell lung cancer: a phase III trial. Lung Cancer 2006; 52 (2): 155–63.Park J.O., Kim S.W., Ahn J.S. et al. Phase III trial of two vs four additional cycles in patients who are nonprogressive after two cycles of platinum - based chemotherapy in non - small cell lung cancer. J Clin Oncol 2007; 25 (33): 5233–9.Fidias P.M., Dakhil S.R., Lyss A.P. et al. Phase III study of immediate compared with delayed docetaxel after front - line therapy with gemcitabine plus carboplatin in advanced non - small cell lung cancer. J Clin Oncol 2009; 27 (4): 591–8.Belani C.P., Perry M.C., La Rocca R.V. et al. Maintenance therapy (MT) with weekly paclitaxel improves outcome for advanced non - small cell lung cancer (NSCLC) patients. J Clin Oncol (Meeting Abstr.) 2005; 23 (16s): 7143.Sandler A, Gray R, Perry M.C. et al. Paclitaxel - carboplatin alone or with bevacizumab for non - small cell lung cancer. New Engl J Med 2006; 355 (24): 2542–50.Manegold C, von Pawel J, Zatloukal P et al. A phase III randomised study of first - line bevacizumab combined with cisplatin/gemcitabine (CG) in patients with advanced or recurrent non - squamous, non - small cell lung cancer (NSCLC). Presented at the 33rd ESMO Congress, September 12–16, 2008; Stockholm, Sweden. Abstr. LBA1. Ann Oncol 2008; 19 (Suppl. 8): 8.Prior C, Oroszy S, Oberaigner W et al. Advanced non - small cell lung cancer: adjunctive interferon-g in induction and maintenance therapy. J Cancer Research Clin Oncol 1999; 125 (1): 42–6.Belani C.P., Ramalingam S, Perry M.C. et al. Randomized, phase III study of weekly paclitaxel in combination with carboplatin vs standard every-3-weeks administration of carboplatin and paclitaxel for patients with previously untreated advanced non - small cell lung cancer. J Clin Oncol 2008; 26 (3): 468–73.Adjei A.A. Pemetrexed (Alimta): a novel multitargeted antifolate agent. Exp Rev Anticancer Therapy 2003; 3 (2): 145–56.Mendelsohn L.G., Shih C, Chen V.J. et al. Enzyme inhibition, polyglutamation, and the effect of LY231514 (MTA) on purine biosynthesis. Semin Oncol 1999; 26 (2 Suppl. 6): 42–7.Shih C, Chen V.J., Gossett L.S. et al. LY231514, a pyrrolo [2,3-d] pyrimidine-based antifolate that inhibits multiple folate - requiring enzymes. Cancer Research 1997; 57 (6): 1116–23.Chen V.J., Bewley J.R., Andis S.L. et al. Preclinical cellular pharmacology of LY231514 (MTA): a comparison with methotrexate, LY309887 and raltitrexed for their effects on intracellular folate and nucleoside triphosphate pools in CCRF-CEM cells. Brit J Cancer 1998; 78 (Suppl. 3): 27–34.Alimta (package insert). Indianapolis IN. Eli Lilly Company 2012.Belani C.P., Wu Y.L., Chen Y.M. et al. Efficacy and safety of pemetrexed maintenance therapy vs best supportive care in patients from East Asia with advanced, non - squamous non - small cell lung cancer: an exploratory subgroup analysis of a global, randomized, phase 3 clinical trial. J Thorac Oncol 2012; 7: 567–73.Belani C.P., Brodowicz T, Ciuleanu T.E. et al. Quality of life in patients with advanced non - small cell lung cancer given maintenance treatment with pemetrexed vs placebo (H3E-MC-JMEN): results from a randomized, double - blind, phase 3 study. Lancet Oncol 2012; 13 (3): 292–9.Ciuleanu T, Brodowicz T, Zielinski C et al. Maintenance pemetrexed plus best supportive care vs placebo plus best supportive care for non - small cell lung cancer: a randomised, double - blind, phase 3 study. Lancet 2009; 374 (9699): 1432–40.Paz-Ares L, de Marinis F, Dediu M et al. Maintenance therapy with pemetrexed plus best supportive care vs placebo plus best supportive care after induction therapy with pemetrexed plus cisplatin for advanced non - squamous non - small cell lung cancer (PARAMOUNT): a double - blind, phase 3, randomised controlled trial. Lancet Oncol 2012; 13 (3): 247–55.Paz-Ares L, de Marinis F, Dediu M et al. PARAMOUNT: Final overall survival (OS) results of the phase III study of maintenance pemetrexed (pem) plus best supportive care (BSC) vs placebo (plb) plus BSC immediately following induction treatment with pem plus cisplatin (cis) for advanced nonsquamous (NS) non - small cell lung cancer (NSCLC). Ann Meet Am Society Clin Oncol 2012; Chicago, Illinois. Abstr. LBA7507. J Clin Oncol 2012; 30 (Suppl. 18).Cappuzzo F, Ciuleanu T, Stelmakh L et al. SATURN: A double - blind, randomized, phase III study of maintenance erlotinib vs placebo following non - progression with first - line platinum - based chemotherapy in patients with advanced NSCLC. Lancet Oncol 2010; 11 (6): 521–9.Edelman M.J., Le Chevalier T, Soria J.C. Maintenance therapy and advanced non - small cell lung cancer: a skeptic’s view. J Thorac Oncol 2012; 7 (9): 1331–6.Pirker R, Pereira J.R., Szczesna A et al. Cetuximab plus chemotherapy in patients with advanced non - small cell lung cancer (FLEX): an open - label randomised phase III trial. Lancet 2009; 373 (9674): 1525–31.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 (21): 3543–51.National Comprehensive Cancer Network®. NCCN Clinical Practice Guidelines in OncologyTM: Non - Small Cell Lung Cancer 2009. http://www.nccn.orgHensing T.A., Schell M.J., Lee J.H. et al. Factors associated with the likelihood of receiving second line therapy for advanced non - small cell lung cancer. Lung Cancer 2005; 47 (2): 253–9.de Marinis F, Pereira J.R., Fossella F et al. Lung Cancer Symptom Scale outcomes in relation to standard efficacy measures: an analysis of the phase III study of pemetrexed vs docetaxel in advanced non - small cell lung cancer. J Thorac Oncol 2008; 3 (1): 30–6.