Clinical Oncology and Cancer Research

, Volume 8, Issue 4, pp 235–241 | Cite as

Pemetrexed monotherapy and pemetrexed plus platinum combination therapy as non-first-line treatments for advanced non-small cell lung cancer

  • Fang Wang
  • Gui-fang Guo
  • Hui-juan Qiu
  • Xu-xian Chen
  • Pi-li Hu
  • Fei-fei Zhou
  • Wen-zhuo He
  • Bei Zhang
  • Liang-ping XiaEmail author



Data on the efficacy profiles of pemetrexed monotherapy and pemetrexed plus platinum combination therapy in the non-first-line setting for patients with advanced non-small cell lung cancer (NSCLC) are limited, and previous studies have reported contradictory results. This study investigated and compared the efficacy and toxicity profiles of these two regimens to provide a broader understanding of their dynamics.


Previously treated patients with advanced and/or recurrent NSCLC who received pemetrexed monotherapy or pemetrexed plus platinum combination therapy between January 1, 2006, and December 31, 2009, at Sun Yat-sen University Cancer Center were evaluated. The primary endpoint of this study was progression-free survival (PFS), whereas the secondary endpoints were overall response rate (ORR), disease control rate (DCR), overall survival (OS), and toxicity. Survival was analyzed using the Kaplan-Meier method. Univariate analysis was performed to identify the factors potentially influencing OS, and chi-square analysis was carried out to compare ORR and DCR.


Forty-six patients with advanced and/or recurrent NSCLC were analyzed; of these patients, 25 were given pemetrexed monotherapy and 21 received pemetrexed plus platinum combination therapy. The following correspond to the rates recorded for the pemetrexed monotherapy group and the pemetrexed plus platinum group: median PFS, 1.97 and 2.3 months (P=0.565); median OS, 30. 93 and 30.33 months (P=0.877); ORR, 8% (2/25) and 9.5% (2/21) (P=0.857); and DCR, 32% (8/25) and 57.1% (12/21) (P=0.09). Univariate analysis revealed that no factor was correlated with OS from NSCLC (P>0.05 for all). Gastrointestinal toxicity in the pemetrexed plus platinum group was modestly higher than that in the pemetrexed monotherapy group (P=0.034), but other adverse events were similar between the groups.


Compared with pemetrexed monotherapy, pemetrexed plus platinum combination therapy causes more gastrointestinal toxicities and does not exhibit improved efficacy, in terms of ORR, DCR, PFS, and OS, in the non-first-line setting for NSCLC. However, further research with a higher patient population is necessary to validate this finding.

Key Words

pemetrexed non-small cell lung cancer efficacy safety non-first-line setting 



non-small cell lung cancer


complete response


partial response


stable disease


progressive disease


overall response rate


disease control rate


overall survival


progression-free survival


performance status


epidermal growth factor receptor


tyrosine kinase inhibitor


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  1. 1.
    Schiller JH, Harrington D, Belani CP, et al. Eastern Cooperative Oncology Group. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med 2002; 346: 92–98.PubMedCrossRefGoogle Scholar
  2. 2.
    Parkin DM, Bray F, Ferlay J, et al. Global cancer statistics, 2002. CA Cancer J Clin 2005; 55:74–108.PubMedCrossRefGoogle Scholar
  3. 3.
    Paez JG, Jänne PA, Lee JC, et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 2004; 304: 1497–1500.PubMedCrossRefGoogle Scholar
  4. 4.
    Mok TS, Wu YL, Thongprasert S, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 2009; 361: 947–957.PubMedCrossRefGoogle Scholar
  5. 5.
    Maemondo M, Inoue A, Kobayashi K, et al. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med 2010; 362: 2380–2388.PubMedCrossRefGoogle Scholar
  6. 6.
    Rosell R, Moran T, Queralt C, et al. Screening for epidermal growth factor receptor mutations in lung cancer. N Engl J Med 2009; 361: 958–967.PubMedCrossRefGoogle Scholar
  7. 7.
    Chiappori A, Bepler G, Barlesi F, et al. Phase II, double-blinded, randomized study of enzastaurin plus pemetrexed as second-line therapy in patients with advanced non-small cell lung cancer. J Thorac Oncol. 2010; 5: 369–375.PubMedCrossRefGoogle Scholar
  8. 8.
    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): P2-328. J Thorac Oncol 2007; 2: S851.CrossRefGoogle Scholar
  9. 9.
    Zinner RG, Novello S, Peng G, Herbst R, Obasaju C, Scagliotti G. Comparison of Patient Outcomes According to Histology Among Pemetrexed-Treated Patients With Stage IIIB/IV Non-Small-Cell Lung Cancer in Two Phase II Trials. Clinical Lung Cancer. 2010; 11: 126–131.PubMedCrossRefGoogle Scholar
  10. 10.
    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: 5929–5937.PubMedCrossRefGoogle Scholar
  11. 11.
    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: a multicenter, randomized, phase II trial. J Thorac Oncol 2007; 2: 221–229.PubMedCrossRefGoogle Scholar
  12. 12.
    Comella P, Chiuri VE, De Cataldis G, et al. Gemcitabine combined with either pemetrexed or paclitaxel in the treatment of advanced non-small cell lung cancer: A randomized phase II SICOG trial. Lung Cancer 2010; 68: 94–98.PubMedCrossRefGoogle Scholar
  13. 13.
    Peacock NW, Spigel DR, Hainsworth JD, et al. A phase II trial of biweekly pemetrexed (P) and gemcitabine (G) in the first-line treatment (tx) of patients (pts) with advanced non-small cell lung cancer (NSCLC). J Clin Oncol 2006; 24: A17054.Google Scholar
  14. 14.
    West HL, Wakelee HA, Perry MC, Belt RJ, Chen R, Obasaju C. Gemcitabine and pemetrexed administered in rapid sequence as front-line chemotherapy for advanced nonsmall-cell lung cancer: a phase II clinical trial. Ann Oncol 2009; 20: 850–856.PubMedCrossRefGoogle Scholar
  15. 15.
    Grønberg BH, Bremnes RM, Fløtten 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-smallcell lung cancer. J Clin Oncol. 2009; 27: 3217–3224.PubMedCrossRefGoogle Scholar
  16. 16.
    Scagliotti G, 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 NSCLC. J Clin Oncol 2008; 26: 3543–3551.PubMedCrossRefGoogle Scholar
  17. 17.
    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; 22:1589–1597.PubMedCrossRefGoogle Scholar
  18. 18.
    Shepherd FA, Rodrigues Pereira J, Ciuleanu T, et al. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med. 2005; 353: 123–132.PubMedCrossRefGoogle Scholar
  19. 19.
    Shepherd FA, Dancey J, Ramlau R, et al. Prospective randomized trial of docetaxel versus best supportive care in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy. J Clin Oncol 2000;18: 2095–2103.PubMedGoogle Scholar
  20. 20.
    Zhang YF, Chen ZW, Lu S. Pemetrexed monotherapy versus pemetrexed plus platinum combination as secondline treatment for advanced non-small cell lung cancer. Chin Med J 2009; 122: 2472–2476.PubMedGoogle Scholar
  21. 21.
    Smit EF, Burgers SA, Biesma B, et al. Randomized phase II pharmacogenetic study of pemetrexed compared with pemetrexed plus carboplatin in pretreated patients with advanced non-small-cell lung cancer. J Clin Oncol 2009; 27: 2038–2045.PubMedCrossRefGoogle Scholar
  22. 22.
    Cullen MH, Zatloukal P, Sörenson S, et al. A randomized phase III trial comparing standard and high-dose pemetrexed as second-line treatment in patients with locally advanced or metastaticnon-small-cell lung cancer. Ann Oncol 2 2008;19: 939–945.CrossRefGoogle Scholar
  23. 23.
    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 patients with nonsmall cell lung cancer. Clin Cancer Res 2008; 14: 4206–4212.PubMedCrossRefGoogle Scholar
  24. 24.
    Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009; 45: 228–247.PubMedCrossRefGoogle Scholar
  25. 25.
    Trotti A, Colevas AD, Setser A, Basch E. CTCAE v3.0: development of a comprehensive grading system for the adverse effects of cancer treatment. Semin Radiat Oncol 2003; 13: 176–181.PubMedCrossRefGoogle Scholar
  26. 26.
    Cohen MH, Johnson JR, Wang YC, Sridhara R, Pazdur R. FDA drug approval summary: Pemetrexed for injection (Alimta) for the treatment of non-small cell lung cancer. Oncologist 2005; 10: 363–368.PubMedCrossRefGoogle Scholar
  27. 27.
    Kim YH, Kim JS, Choi YH, et al. Phase II study of docetaxel and cisplatin combination chemotherapy in metastatic or unresectable localized non-small-cell lung cancer. Int J Clin Oncol 2002; 7: 114–119.PubMedGoogle Scholar
  28. 28.
    D’Addario G, Pintilie M, Leighl NB, Feld R, Cerny T, Shepherd FA. Platinum-based versus non-platinum-based chemotherapy in advanced non-small-cell lung cancer: a meta-analysis of the published literature. J Clin Oncol 2005; 23: 2926–36.PubMedCrossRefGoogle Scholar
  29. 29.
    Chang MH, Ahn JS, Lee J, et al. The efficacy of pemetrexed as a third-or fourth-line therapy and the significance of thymidylate synthase expression in patients with advanced non-small cell lung cancer. Lung Cancer 2010; 69: 323–329.PubMedCrossRefGoogle Scholar
  30. 30.
    Grimminger PP, Schneider PM, Metzger R, et al. Low thymidylate synthase, thymidine phosphorylase, and dihydropyrimidine dehydrogenase mRNA expression correlate with prolonged survival in resected non-smallcell lung cancer. Clin Lung Cancer. 2010; 11: 328–334.PubMedCrossRefGoogle Scholar
  31. 31.
    Thatcher N, Chang A, Parikh P, et al. Gefitinib plus best supportive care in previously treated patients with refractory advanced non-small-cell lung cancer: results from a randomised, placebo-controlled, multicentre study (Iressa Survival Evaluation in Lung Cancer). Lancet 2005; 366: 1527–1537.PubMedCrossRefGoogle Scholar
  32. 32.
    Jalal S, Waterhouse D, Edelman MJ, et al. Pemetrexed plus cetuximab in patients with recurrent non-small cell lung cancer (NSCLC). A phase I/II study from the Hoosier Oncology Group. J Thorac Oncol. 2009; 4: 1420–1424.PubMedCrossRefGoogle Scholar
  33. 33.
    De Boer R, Arrieta Ó, Gottfried M, et al. Vandetanib plus pemetrexed versus pemetrexed as second-line therapy in patients with advanced non-small cell lung cancer (NSCLC): a randomized, double-blind phase III trial (ZEAL). J Clin Oncol 2009; 27: A8010.Google Scholar
  34. 34.
    Adjei AA, Mandrekar SJ, Dy GK, et al. Phase II trial of pemetrexed plus bevacizumab for second-line therapy of patients with advanced non-small-cell lung cancer: NCCTG and SWOG study N0426. J Clin Oncol 2010; 28: 614–619.PubMedCrossRefGoogle Scholar
  35. 35.
    Molina JR, Adjei AA. The role of Pemetrexed (Alimta®, LY231514) in lung cancer therapy. Clin Lung Cancer 2003; 5: 21–27.PubMedCrossRefGoogle Scholar

Copyright information

© Tianjin Medical University Cancer Institute and Hospital and Springer Berlin Heidelberg 2011

Authors and Affiliations

  • Fang Wang
    • 1
    • 2
  • Gui-fang Guo
    • 1
    • 2
  • Hui-juan Qiu
    • 1
    • 2
  • Xu-xian Chen
    • 1
    • 2
  • Pi-li Hu
    • 1
    • 2
  • Fei-fei Zhou
    • 3
  • Wen-zhuo He
    • 1
    • 2
  • Bei Zhang
    • 1
    • 2
  • Liang-ping Xia
    • 1
    • 2
    Email author
  1. 1.State Key Laboratory of Oncology in South ChinaGuangzhouGuangdong Province, China
  2. 2.VIP RegionSun Yat-sen University Cancer CenterGuangzhouGuangdong Province, China
  3. 3.Tumor CenterThe Foshan First People’s HospitalFoshanGuangdong Province, China

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