Pharmacology and mechanism of action of pemetrexed

Research output: Contribution to journalReview article

54 Citations (Scopus)

Abstract

Pemetrexed is a novel multitargeted antifolate that inhibits ≥ 3 enzymes involved in folate metabolism and purine and pyrimidine synthesis. These enzymes are thymidylate synthase, dihydrofolate reductase, and glycinamide ribonucleotide formyltransferase. This agent has broad antitumor activity in phase II trials in a wide variety of solid tumors, and is approved in combination with cisplatin for the therapy of malignant mesothelioma. In a recent phase III trial, pemetrexed demonstrated equivalent efficacy to docetaxel, but with significantly less toxicity, in second-line treatment of non-small-cell lung cancer. The most common and serious toxicities of pemetrexed - myelosuppresion and mucositis - have been significantly ameliorated by folic acid and vitamin B12 supplementation. More important, vitamin supplementation has not been shown to adversely affect efficacy in some tumor types. Tumors with codeletion of the methylthioadenosine phosphorylase gene, as a consequence of p16 deletions, may be particularly sensitive to pemetrexed. In this review, the biochemistry and mechanism of action of pemetrexed are discussed.

Original languageEnglish (US)
JournalClinical Lung Cancer
Volume5
Issue numberSUPPL. 2
DOIs
StatePublished - Jan 1 2004

Fingerprint

Pemetrexed
Pharmacology
docetaxel
Folic Acid
Hydroxymethyl and Formyl Transferases
Folic Acid Antagonists
Neoplasms
Mucositis
Enzymes
Vitamin B 12
Vitamins
Non-Small Cell Lung Carcinoma
Biochemistry
Cisplatin
Genes

Keywords

  • Antimetabolites
  • Mucositis
  • Multitargeted antifolate
  • Myelosuppression
  • Vitamin supplementation

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

Cite this

Pharmacology and mechanism of action of pemetrexed. / Adjei, Alex.

In: Clinical Lung Cancer, Vol. 5, No. SUPPL. 2, 01.01.2004.

Research output: Contribution to journalReview article

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