[Pemetrexed]

Abstract

Pemetrexed (ALIMTA, LY231514) is a novel, multi targeted antifolate chemotherapy agent that is active in various tumors including mesothelioma, NSCLC, breast, colon and bladder carcinoma. Pemetrexed inhibits several enzymes in the folate pathway including thymidylate synthase, dihydrofolate reductase, and glycinamide ribonucleotide formyltransferase. Pemetrexed is approved in the United States and a number of European Union countries for use in the treatment of mesothelioma, and the second-line treatment of advanced NSCLC. However, in Japan, pemetrexed was approved for use only in combination with cisplatin in the treatment of mesothelioma in January 2007. This approval was granted on the basis of a phase III trial of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. Treatment with pemetrexed plus cisplatin and vitamin supplementation, resulted in superior survival time, time to progression, and response rates compared with treatment with cisplatin alone. In addition, in a phase III trial of pemetrexed versus docetaxel in patients with NSCLC previously treated with chemotherapy, treatment with pemetrexed resulted in clinically equivalent efficacy outcomes, but with significantly fewer side effects including grade 3 or 4 neutropenia , neutropenic fever, and alopecia, compared with docetaxel. Therefore, pemetrexed should be considered a standard treatment option for second-line NSCLC in US and most of EU. Addition of folic acid and vitamin B12 significantly reduced the toxicity of pemetrexed, especially hematologic toxicity and gastrointestinal toxicity. Pemetrexed is the expected agent for use in high risk patients, especially elderly or poor performance status patients.