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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Pemetrexed safety and dosing strategy.

Pemetrexed is a novel antifolate/antimetabolite that inhibits several folate-dependent enzymes, including thymidylate synthase, dihydrofolate reductase, and glycinamide ribonucleotide transformylase. As a class, antifolates have been associated with sporadic severe myelosuppression with gastrointestinal toxicity. Although infrequent, a combination of such toxicities carries a high risk of potentially life-threatening complications. Severe toxicity from pemetrexed-based therapy has become more predictable using the vitamin deficiency marker homocysteine and, to a lesser extent, methylmalonic acid. Evidence now suggests that reducing total plasma homocysteine levels by supplementation with folic acid and vitamin B(12) leads to a better safety profile for pemetrexed, while not adversely affecting its efficacy.[1]


  1. Pemetrexed safety and dosing strategy. Niyikiza, C., Hanauske, A.R., Rusthoven, J.J., Calvert, A.H., Allen, R., Paoletti, P., Bunn, P.A. Semin. Oncol. (2002) [Pubmed]
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