The role of pemetrexed in the pharmacotherapy of malignant pleural mesothelioma

Among newer cytotoxic agents, pemetrexed gained much interest because of its particular mechanism of action. In fact, pemetrexed is a multi-target agent able to inhibit at least three crucial enzymes involved in the folate pathway: thymidylate synthase, dihydrofolate reductase and glycinamide ribonucleotide formyl transferase. The ability to inhibit multiple enzymes, confers to this drug a clinical advantage by increasing the spectrum of tumors with biochemical profiles potentially sensitive to the drug. Due to the good toxicity profile of pemetrexed, the combination with cisplatin resulted feasible and effective. Pemetrexed is currently approved in combination with cisplatin for frst line treatment in patients with unresectable malignant pleural mesothelioma. Pemetrexed is the frst agent approved for the treatment of malignant pleural mesothelioma. Generally, pemetrexed is considered a well tolerated drug and the addition of folic acid, vitamin B12, and dexamethasone markedly reduced the incidence of grade 3 and 4 hematologic and non-hematologic toxicities. Pharmacology, pharmacokinetics, efficacy, safety, and current and potential roles of pemetrexed in therapy for malignant pleural mesothelioma were reviewed.