Pemetrexed (Alimta): improving outcomes in malignant pleural mesothelioma.
During the past four decades, chemotherapy has failed to demonstrate a consistent clinical benefit for patients with unresectable or recurrent malignant pleural mesothelioma (MPM). Consequently, there has been no standard chemotherapy nor US Food and Drug Administration (FDA)-approved drug for patients with this disease. The introduction of pemetrexed (Alimta, Eli Lilly), a multitargeted antifolate agent, has improved the outlook for patients with mesothelioma by demonstrating a positive impact on quality of life and by prolonging survival. Pemetrexed is the first FDA-approved drug for the treatment of MPM. The combination of cisplatin plus pemetrexed is now the standard of care for the treatment of the disease. Furthermore, supplementation with vitamin B12 and folate has vastly improved the toxicity profile of pemetrexed. This article summarizes historical chemotherapy trials in MPM; discusses key features of clinical trial design for MPM; summarizes the results of a landmark Phase III trial of pemetrexed and cisplatin in MPM; discusses the relative contributions of pemetrexed and cisplatin to the regimen; explains the importance of vitamin supplementation of pemetrexed; and provides direction for future clinical trials in this disease.
Budde
Leanne S
LS
Indiana University School of Medicine, Division of Hematology/Oncology, 535 Barnhill Drive, Room 473, Indianapolis, IN 46202 USA. lbudde@iupui.edu
Hanna
Nasser H
NH
D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005971:Glutamates / Q000627:therapeutic use*; D006147:Guanine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D006801:Humans; D008654:Mesothelioma / Q000188:drug therapy*; D000068437:Pemetrexed; D010997:Pleural Neoplasms / Q000188:drug therapy*; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors*
D000964:Antimetabolites, Antineoplastic; D004791:Enzyme Inhibitors; D005971:Glutamates; D000068437:Pemetrexed; D006147:Guanine; D013940:Thymidylate Synthase