Pemetrexed in Malignant Pleural Mesothelioma
November 02, 2004
Malignant pleural mesothelioma (MPM) is a disease with a poorprognosis, related in part to the aggressiveness of this disease, and inpart due to the lack of drugs that have demonstrated tumor activity.Historically, antifolates such as methotrexate have been the most activedrugs in the treatment of mesothelioma. Newer antifolates haverecently demonstrated higher efficacy than older regimens in the treatmentof this rare disease. One of these agents, pemetrexed (Alimta),has been evaluated both as a single agent and as part of a combinationregimen. Pemetrexed has been studied in three trials in patients withMPM, and two phase I trials included patients with MPM. In a phaseII trial, pemetrexed was studied as a single agent in patients with MPM.Seven of 64 patients achieved partial responses, with a median overallsurvival of 10.7 months. A large, randomized, phase III trial was conductedto compare pemetrexed/cisplatin with cisplatin. The responserate was 41.3% compared with 16.7%, median survival was 12.1 monthscompared with 9.3 months, and 1-year survival was 50.3% vs 38% inthe pemetrexed/cisplatin and cisplatin arms, respectively. The combinationof pemetrexed/cisplatin also demonstrated superiority in qualityof life and pulmonary functioning analysis when compared withcisplatin.