Pemetrexed: a multitargeted antifolate

Area of Science:

• Oncology
• Pharmacology

Background:

• Pemetrexed (Alimta) gained FDA approval in 2004 for malignant pleural mesothelioma (MPM) and later for non-small cell lung cancer (NSCLC).
• It is the first agent approved for MPM treatment.
• Pemetrexed is a multitargeted antifolate chemotherapy agent.

Purpose of the Study:

• To review the pharmacology, pharmacokinetics, efficacy, and safety of pemetrexed.
• To examine the current and potential therapeutic roles of pemetrexed in MPM, NSCLC, and other cancers.

Main Methods:

• Literature search of PubMed, International Pharmaceutical Abstracts, and ASCO proceedings (1966-2004).
• Inclusion of published literature and scientific meeting abstracts/posters.
• Search terms included pemetrexed, Alimta, mesothelioma, MPM, NSCLC, and other relevant terms.

Main Results:

• Pemetrexed plus cisplatin showed higher response rates (41.3%) and longer median survival (12.1 months) in MPM compared to cisplatin alone (16.7%, 9.3 months).
• In NSCLC, pemetrexed demonstrated comparable efficacy to docetaxel in response rates and survival, with significantly fewer hematologic toxicities and less alopecia.
• Folic acid and vitamin B12 supplementation were found to significantly decrease pemetrexed toxicity.

Conclusions:

• Pemetrexed exhibits antitumor activity in various cancers as a single agent or in combination.
• Its efficacy in MPM with cisplatin is established, and its use in NSCLC is supported by surrogate endpoints.
• Supplementation with folic acid and vitamin B12 markedly reduces pemetrexed-related toxicity.