Pemetrexed alone and in combination with platinum compounds in the management of malignant mesothelioma

Malignant pleural mesothelioma is an aggressive but rare malignancy with a dismal prognosis. It is traditionally resistant to chemotherapy. Antifolate agents have recently shown promising data in the treatment of this malignancy. Pemetrexed is a multitargeted antifolate inhibitor of thymidylate synthase and other folate-dependent enzymes that has emerged as one of the most active agents in this disease. Several phase I/II trials of pemetrexed as a single agent or in combination with a platinum drug have demonstrated considerable activity in mesothelioma. In a recently published phase III randomized study, pemetrexed/cisplatin showed a significant improvement in survival, response rate, and quality of life compared with single-agent cisplatin. In addition, several trials reported that folic acid and vitamin B12 supplementation significantly reduced the toxicity observed with the use of pemetrexed without affecting the efficacy of the drug.