Pemetrexed is a novel multitargeted antifolate analog. The drug has shown encouraging activity in a wide range of solid tumors, including cervix, head and neck, and bladder carcinomas, which are the focus of this review. Toxicity, particularly hematologic, is higher in patients with these tumor types than in other populations exposed to pemetrexed. Supplementation with folic acid and vitamin B(12) appears to effectively reduce the incidence of severe toxicity and may optimize the therapeutic index of pemetrexed in patient subsets with poor nutritional status. The role of this agent in the management of these and other tumor types, as a single agent or in combination, shall be determined by randomized phase III studies.
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