Schedule-Dependent Synergistic Effect of Pemetrexed Combined with Gemcitabine against Malignant Pleural Mesothelioma and Non-Small Cell Lung Cancer Cell Lines

Chemotherapy. 2008 Jun 18;54(3):166-175. [Epub ahead of print] [Link]

Nagai S, Takenaka K, Sonobe M, Wada H, Tanaka F.

Department of Thoracic Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.

Abstract

Background: Pemetrexed, a multi-targeted antifolate (MTA), is a promising agent in the treatment of malignant pleural mesothelioma (MPM) and non-small cell lung cancer (NSCLC). With the aim of finding an optimal schedule for the combination therapy of MTA and gemcitabine (GEM), we investigated their interaction against an MPM cell line, 211H, and the NSCLC cell lines A549 and H1299.

Methods: Combination index analysis was used in 3 different schedules. Cell cycle analysis by flow cytometry and real-time RT-PCR analysis of thymidylate synthase (TS), folylpolyglutamate synthetase (FPGS) and reduced folate carrier 1 (RFC1) genes were performed to understand the biological consequences of their interaction.

Results: MTA showed potent cytotoxicity against 211H cells (IC₅₀

Conclusion: Sequential administration of MTA and GEM is active, and the schedule of MTA followed by GEM is recommended for treating MPM.

Keywords: Pemetrexed, Gemcitabine, Pleural mesothelioma, Lung cancer, Combination chemotherapy