Pemetrexed safety and dosing strategy Journal Articles uri icon

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  • 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.


  • Niyikiza, Clet
  • Hanauske, Axel-R
  • Rusthoven, James
  • Calvert, A Hilary
  • Allen, Robert
  • Paoletti, Paolo
  • Bunn, Paul A

publication date

  • December 2002