Pemetrexed in malignant pleural mesothelioma

Malignant pleural mesothelioma (MPM) is a disease with a poor prognosis, related in part to the aggressiveness of this disease, and in part due to the lack of drugs that have demonstrated tumor activity. Historically, antifolates such as methotrexate have been the most active drugs in the treatment of mesothelioma. Newer antifolates have recently demonstrated higher efficacy than older regimens in the treatment of this rare disease. One of these agents, pemetrexed (Alimta), has been evaluated both as a single agent and as part of a combination regimen. Pemetrexed has been studied in three trials in patients with MPM, and two phase I trials included patients with MPM. In a phase II trial, pemetrexed was studied as a single agent in patients with MPM. Seven of 64 patients achieved partial responses, with a median overall survival of 10.7 months. A large, randomized, phase III trial was conducted to compare pemetrexed/cisplatin with cisplatin. The response rate was 41.3% compared with 16.7%, median survival was 12.1 months compared with 9.3 months, and 1-year survival was 50.3% vs 38% in the pemetrexed/cisplatin and cisplatin arms, respectively. The combination of pemetrexed/cisplatin also demonstrated superiority in quality of life and pulmonary functioning analysis when compared with cisplatin.