title: Pemetrexed safety and dosing strategy.
abstract: 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.
authors.affiliation: Eli Lilly and Company, Indianapolis, IN 46285, USA.
authors.forename: Clet
authors.initials: C
authors.lastname: Niyikiza
authors.forename: Axel-R
authors.initials: AR
authors.lastname: Hanauske
authors.forename: James J
authors.initials: JJ
authors.lastname: Rusthoven
authors.forename: A Hilary
authors.initials: AH
authors.lastname: Calvert
authors.forename: Robert
authors.initials: R
authors.lastname: Allen
authors.forename: Paolo
authors.initials: P
authors.lastname: Paoletti
authors.forename: Paul A
authors.initials: PA
authors.lastname: Bunn
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D002986:Clinical Trials as Topic; D005492:Folic Acid / Q000008:administration & dosage; D005493:Folic Acid Antagonists / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D005971:Glutamates / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D006147:Guanine / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D006710:Homocysteine / Q000097:blood; D006801:Humans; D008764:Methylmalonic Acid / Q000097:blood; D009369:Neoplasms / Q000188:drug therapy; D000068437:Pemetrexed; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors*; D014805:Vitamin B 12 / Q000008:administration & dosage
chemical_list: D000964:Antimetabolites, Antineoplastic; D005493:Folic Acid Antagonists; D005971:Glutamates; D000068437:Pemetrexed; D006710:Homocysteine; D006147:Guanine; D008764:Methylmalonic Acid; D005492:Folic Acid; D013940:Thymidylate Synthase; D014805:Vitamin B 12