Pemetrexed (Alimta): a novel multitargeted antifolate agent

Alex A Adjei
Expert Review of Anticancer Therapy 2003, 3 (2): 145-56
Pemetrexed (Alimta) is a novel, multitargeted antifolate that inhibits at least three of the enzymes involved in folate metabolism, and purine and pyrimidine synthesis. These enzymes are thymidylate synthase, dihydrofolate reductase and glycinamide ribonucleotide formyltransferase. Pemetrexed has demonstrated broad antitumor activity in Phase II trials in a wide variety of solid tumors, including mesothelioma, non-small cell lung, breast, cervical, colorectal, head and neck, and bladder cancers. Promising activity has also been demonstrated when pemetrexed is combined with cisplatin and gemcitabine (Gemzar). A pivotal Phase III study in mesothelioma has been presented. This study indicates the superiority of pemetrexed in combination with cisplatin versus cisplatin alone in this disease. The most significant toxicities of pemetrexed, myelosuppression and mucositis have been significantly ameliorated by folate and vitamin B12 supplementation. More importantly, vitamin supplementation has not demonstrated any adverse efficacy. This review discusses the biochemistry and clinical activity of pemetrexed.

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