1. Jemal A, Siegel R, Ward E et al. Cancer statistics. CA Cancer J Clin 2008; 58: 71–96.
2. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin 2005; 55: 74–108.
3. Schiller JH, Harrington D, Belani CP et al. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med 2002; 346: 92–8.
4. Scagliotti G, Hanna N, Fossella F et al. The differential efficacy of pemetrexed according to NSCLC histology: a review of two phase III studies. Oncologist 2009; 14: 253–63.
5. Shih C, Chen VJ, Gossetti LS et al. LY231514, a pirrolo[2,3-d]pyrimidine-based antifolate that inhibitsmultiple folate requiring enzymes. Cancer Res 1997; 57: 1116–23.
6. Schultz RM, Chen VJ, Bewley JR et al. Biological activity of the multitargeted antifolate, MTA (LY231514), in human cell lines with different resistance mechanisms to antifolate drugs. Sem Oncol 1999; 26 (Suppl. 6): 68–73.
7. Ceppi P, Volante M, Saviozzi S et al. Squamous cell carcinoma of the lungcompared with other histotypes shows higher messenger RNA and protein levels for thymidylate synthetase. Cancer 2006; 107: 1589–96.
8. Scagliotti G, Monica V, Ceppi P et al. Baseline thymidylate synthetase expression according to histological subtypes of nonsmall cell lung cancer. J Clin Oncol 2009; 27 (15S): 387s [abstract 7521].
9. Huang CL, Liu D, Nakano J et al. E2F1 overexpression correlates with thymidylate synthase and survivin gene expressions and tumor proliferation in non small-cell lung cancer. Clin Cancer Res 2007; 13: 6938–46.
10. Salon C, Merdzhanova G, Brambilla C et al. E2F-1, Skp2 and cyclin E oncoproteins are upregulated and directly correlated in high-grade neuroendocrine lung tumors. Oncogene 2007; 26: 6927–36.
11. Hanauske AR, Eismann U, Oberschmidt O et al. In vitro chemosensitivity of freshly explanted tumor cells to pemetrexed is correlated with target gene expression. Invest New Drugs 2007; 25: 417–23.
12. Chattopadhyay S, Tamari R, Min SH et al. Commentary: a case for minimizing folate supplementation in clinical regimens with pemetrexed based on the marked sensitivity of the drug to folate availability. Oncologist 2007; 12: 808–15.
13. Vogelzang NJ, Rusthoven JJ, Symanowski J et al. Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol 2003; 21: 2636–44.
14. Hanna N, Shepherd FA, Fossella FV et al. Randomized phase III trial of pemetrexed versus docetaxel in patients with non small cell lung cancer previously treated with chemotherapy. J Clin Oncol 2004; 22: 1589–97.
15. Scagliotti G, Parikh P, von Pawel J et al. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patientswith advanced-stage NSCLC. J Clin Oncol 2008; 26: 3543–51.
16. Niyikiza C, Baker SD, Seitz DE et al. Homocysteine and methylmalonic acid: markers to predict and avoid toxicity from pemetrexed therapy. Mol Cancer Ther 2002; 1: 545–52.
17. Cullen MH, Zatloukal P, Sorenson S et al.  A randomized phase III trial comparing standard and high dose pemetrexed as second-line treatment in patients with locally advanced or metastatic nonsmall cell lung cancer. Ann Oncol 2008; 19: 939–45.
18. Ohe Y, Ichinose Y, Nakagawa K et al. Efficacy and safety of two doses of pemetrexed supplemented with folic acid and vitamin B12 in previously treated patientswith non-small cell lung cancer. Clin Cancer Res 2008; 14: 4206–12.
19. Peterson P, Park K, Fossella F et al. Is pemetrexed more effective in adenocarcinoma and large cell lung cancer than in squamous cell carcinoma? A retrospective analysis of a phase III trial of pemetrexed vs. docetaxel in previously treated patients with advanced non-small cell lung cancer (NSCLC). J Thorac Oncol 2007; 2 (Suppl. 4): S851 [abstract P2-328].
20. Smit EF, Burgers SA, Biesma B et al. Randomized phase II and pharmacogenetic study of pemetrexed compared with pemetrexed plus carboplatin in pretreated patients with advanced non-smallcell lung cancer. J Clin Oncol 2009; 27: 2038–45.
21. Rusthoven JJ, Eisenhauer E, Butts C et al. Multitargeted antifolate LY2311514 as first line chemotherapy for patients with advanced non small cell lung cancer: a phase II study. J Clin Oncol 1999; 17: 1194–9.
22. Clarke SJ, Abratt R, Goedhals L et al. Phase II trial of pemetrexed disodium (ALIMTA, LY231514) in chemotherapy-naive patients with advanced non small cell lung cancer. Ann Oncol 2002; 13: 737–41.
23. Gridelli C, Kaukel E, Gregorc V et al. Single-agent pemetrexed or sequential pemetrexed/gemcitabine as front-line treatment of advanced non-small cell lung cancer in elderly patients or patients ineligible for platinum-based chemotherapy: amulticenter, randomized, phase II trial. J Thorac Oncol 2007; 2: 221–9.
24. Monnerat C, Le Chevalier T, Kelly K et al. Phase II study of pemetrexed-gemcitabine combination in patients with advancedstage non-small cell lung cancer. Clin Cancer Res 2004; 10: 5439–46.
25. Ma CX, Nair S, Thomas S et al. Randomized phase II trial of three schedules of pemetrexed and gemcitabine as front-line therapy for advanced non-small-cell lung cancer. J Clin Oncol 2005; 23: 5929–37.
26. Treat J, Bonomi P, McCleod M et al. Administration ofpemetrexed immediately following gemcitabine as front-line therapy in advanced non-small cell lung cancer: a phase II trial. Lung Cancer 2006; 53: 77–83.
27. Ye Z, Treat JA. Meta-analysis of pemetrexed (P) plus gemcitabine (G) in first-line, advanced (adv) non-small cell lung cancer (NSCLC). J Clin Oncol 2007; 25 (18S): 685s [abstract 18015].
28. Clarke SJ, Boyer MJ, Millward M et al. A phase I/II study of pemetrexed and vinorelbine in patients with non-small cell lung cancer. Lung Cancer 2005; 49: 401–12.
29. Manegold C, GatzemeierU, von Pawel J et al. Frontline treatment of advanced non small cell lung cancer with MTA (LY231514, pemetrexed disodium, ALIMTA) and cisplatin: a multicenter phase II trial. Ann Oncol 2000; 11: 435–40.
30. Shepherd FA, Dancey J, Arnold A et al. Phase II study of pemetrexed disodium, a multitargeted antifolate, and cisplatin as first-line therapy in patients with advanced nonsmall cell lung carcinoma: a study of the National Cancer Institute of Canada Clinical Trials Group. Cancer 2001; 92: 595–600.
31. Scagliotti GV, Kortsik C, Dark GG et al. Pemetrexed combined with oxaliplatin or carboplatin as first-line treatment in advanced non-small cell lung cancer: a multicenter, randomized, phase II trial. Clin Can Res 2005; 11: 690–6.
32. Zinner RG, Fossella FV, Gladish GW et al. Phase II study of pemetrexed in combination with carboplatin in the first-line treatment of advanced nonsmall cell lung cancer. Cancer 2005; 104: 2449–56.
33. Peng G, Zinner RG, Wang Y et al. Comparison of patients outcomes stratified by histology among pemetrexed (P)-treated patients (pts) with stage IIIB/IV non-small cell lung cancer (NSCLC) in two phase II trials. J Clin Oncol 2008; 26 (15S): 447s [abstract 8096].
34. Gronberg BH, Bremnes R, Flotten O et al. Phase III study by the Norwegian Lung Cancer Study Group: pemetrexed plus carboplatin compared with gemcitabine plus carboplatin as first-line chemotherapy in advanced non-small-cell lung cancer. J Clin Oncol 2009; (May 11) [Epub ahead of print].
35. Scagliotti GV, Park K, Patil S et al. Survival without toxicity for cisplatin plus pemetrexed versus cisplatin plus gemcitabine in chemonaпve patients with advanced non-small cell lung cancer: a risk–benefit analysis of a large phase III study. Eur J Cancer 2009; (May 25) [Epub ahead of print].
36. Orlando M, Lee JS, Yang C et al. Efficacy of pemetrexed-cisplatin (PC) in East Asian patients (pts): subgroup analysis of a phase III study comparing PC versus gemcitabine-cisplatin (GC) in first-line treatment of advanced non-small cell lung cancer (NSCLC). J Clin Oncol 2009; 27 (15S): 418s [abstract 8045].
37. Grossi F, Aita M, Follador A et al. Sequential, alternating and maintenance/consolidation chemotherapy in advanced nonsmall cell lung cancer: a review of the literature. Oncologist 2007; 12: 451–64.
38. Belani CP, Brodowicz T, Ciuleanu T et al. Maintenance pemetrexed (Pem) plus best supportive care (BSC) versus placebo (Plac) plus BSC: a randomized phase III study in advanced non-small cell lung cancer (NSCLC). J Clin Oncol 2009; 27 (15S): 806s [abstract CRA8000].
39. Jalal S, Waterhouse D, Edelman M et al. Pemetrexed plus cetuximab in patients (pts) with recurrent non-small cell lung cancer (NSCLC): a phase I-IIa dose-ranging study from the Hoosier Oncology Group. J Clin Oncol 2007; 25 (18S): 433s [abstract 7698].
40. Adjei AA, Mandrekar SJ, Dy GK et al. A phase II second-line study of pemetrexed (pem) in combination with bevacizumab (bev) in patients with advanced non-small cell lung cancer (NSCLC): an NCCTG and SWOG study. J Clin Oncol 2008; 26 (15S): 443s [abstract 8080].
41. Patel JD, Hensing TA, Rademaker A et al. Phase II study of pemetrexed and carboplatin plus bevacizumab with maintenance pemetrexed and bevacizumab as first-line therapy for nonsquamous non-small-cell lung cancer. J Clin Oncol 2009; (May 11) [Epub ahead of print].
42. Waples JM, Auerbach M, Steis R et al. A phase II study of oxaliplatin andpemetrexed plus bevacizumab in advanced non-squamousnonsmall cell lung cancer (An International Oncology Network Study, #I-04-015). J Clin Oncol 2008; 26 (15S): 707s [abstract 19018].
43. Heist RS, Fidias P, Huberman M et al. A phase II study of oxaliplatin, pemetrexed, and bevacizumab in previously treated advanced non-small cell lung cancer. J Thorac Oncol 2008; 3: 1153–8.
44. Casey EM, Harb W, Bradford D et al. Randomized, double blind, multicenter, phase II study of pemetrexed (PEM), carboplatin (CARBO), bevacizumab (BEV) with enzastaurin (ENZ) or placebo (PBO) in chemotherapy-naive patients with stage IIIB/IV non-small cell lung cancer (NSCLC): Hoosier Oncology Group (HOG) LUN06-116. J Clin Oncol 2009; 27 (15S): 415S [abstract 8035].
45. Obasaju CK, Raju RN, Stinchcombe T et al. Final results of a randomized phase II trial of pemetrexed (P) + carboplatin (Cb)±enzastaurin (E) versus docetaxel (D) + Cb as first-line treatment of patients (pts) with stage IIIB/IV non-small cell lung cancer (NSCLC). J Clin Oncol 2009; 27 (15S): 416s [abstract 8037].

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Кафедра онкологии РМАПО, Москва