Pemetrexed therapy for malignant pleural mesothelioma

OBJECTIVE: To review pemetrexed, a novel multi-targeted antifolate agent. DATA SOURCES: A literature search was conducted (1985-September 2004) using MEDLINE and CANCERLIT. Recent abstracts from the American Society of Clinical Oncology were also included, along with the manufacturer's information. Key words were pemetrexed, LY-231514, Alimta, multi-targeted antifolate, malignant pleural mesothelioma. STUDY SELECTION AND DATA EXTRACTION: Relevant information on pharmacology, pharmacokinetics, and safety and efficacy of pemetrexed from clinical trials was selected. DATA SYNTHESIS: Pemetrexed inhibits folate metabolism and purine/pyrimidine synthesis. Based on Phase I and II trials, pemetrexed has antitumor activity in solid tumors such as lung, colorectal, and cervical. A pivotal Phase III study in patients with malignant pleural mesothelioma (MPM) demonstrated survival superiority of pemetrexed-cisplatin regimen versus cisplatin. CONCLUSIONS: Pemetrexed is a promising new drug for the treatment of solid malignancies, most notably MPM.