No abstract

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.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death in the United States. Although chemotherapy has been shown to increase survival for patients with advanced-stage disease, survival benefits have been modest and come at the cost of significant toxicity. Treatment options in the second-line setting have been limited. Pemetrexed, a multitargeted antifolate, has activity as a single agent and as part of combination chemotherapy against NSCLC. As reported in a recent phase III clinical trial, survival outcomes in the second-line setting for patients treated with pemetrexed or docetaxel are similar. More importantly, major toxicity with the use of pemetrexed with vitamin B(12) and folate supplementation is far less than with docetaxel. Based on its single agent activity, ease of administration, and favorable toxicity profile, pemetrexed has the potential to be incorporated in various settings against NSCLC, including metastatic disease, as adjuvant therapy, and for locally advanced disease.