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Pemetrexed is a multi-targeted antifolate that inhibits DNA and RNA synthesis. It is used, with cisplatin, in the treatment of malignant pleural mesothelioma (MPM) in patients who are not candidates for surgery and also as second-line monotherapy in locally advanced or metastatic non-small-cell lung cancer (NSCLC). Pemetrexed has favourable tolerability when supplemented with folic acid and cyanocobalamin (vitamin B12). It is clinically active against both MPM and NSCLC, with activity non-inferior to docetaxel in treating refractory or recurrent NSCLC and, with concomitant cisplatin, superior efficacy to single-agent cisplatin in treating unresectable MPM.