Pemetrexed, a Novel Antifolate Therapeutic Alternative for Cancer Chemotherapy
Pharmacotherapy. 2006 May;26(5):641-54. [Link]
Leticia R. Villela, Pharm.D.1, Brad L. Stanford, Pharm.D.2, Sachin R. Shah, Pharm.D.3
1 School of Pharmacy, Texas Tech University Health Sciences Center, and the Veterans Affairs North Texas Health Care System, Dallas, Texas.
2 School of Pharmacy, Texas Tech University Health Sciences Center, Lubbock, Texas.
3 School of Pharmacy, Texas Tech University Health Sciences Center, and the Veterans Affairs North Texas Health Care System, Dallas, Texas. firstname.lastname@example.org
Address reprint requests to Sachin R. Shah, Pharm.D., BCOP, Texas Tech University Health Sciences Center, School of Pharmacy, 4500 South Lancaster, Building 7, Room 119A, Dallas, TX 75216; School of Pharmacy, Texas Tech University Health Sciences Center, Dallas, 75216, USA.
Pemetrexed is a newly approved antifolate agent for the treatment of malignant pleural mesothelioma (MPM) and metastatic nonâ€“small cell lung cancer (NSCLC). We performed a PubMed/MEDLINE database search to identify relevant literature from January 1966-April 2005. Bibliographies from identified references were searched as well, as were abstracts from the 2004 and 2005 proceedings of the American Society of Clinical Oncology. We discuss the pharmacology of pemetrexed, describing its mechanism of action and comparing it with methotrexate. The pharmacokinetics and pharmacodynamics of pemetrexed are described to provide a better understanding of the properties of this drug. Therapeutic uses are assessed, beginning with the approved indications of MPM and NSCLC. However, pemetrexed has been studied in numerous phase II trials for other types of solid malignancies, and completed trials are reviewed. Data on adverse effects and drug interactions are also provided. Finally, dosing and administration are reviewed, including appropriate premedication. Premedication, including administration of steroids and vitamin supplements, has been shown to decrease the frequency and severity of pemetrexed toxicities. Pemetrexed should be used as a standard of care for unresectable MPM and recurrent metastatic NSCLC.
Keywords: pemetrexed, malignant pleural mesothelioma, MPM, nonâ€“small cell lung cancer, NSCLC, antifolate agent.