An evaluation of pemetrexed in second-line treatment of non-small cell lung cancer.

Pemetrexed is a novel antifolate antimetabolite that targets multiple folate-dependent enzymatic pathways and inhibits multiple enzymes involved in purine and pyrimidine synthesis. Its targets include pathways that, when amplified, are associated with reduced efficacy in conventional cytotoxic agents. As second-line treatment for advanced non-small cell lung cancer, (NSCLC) pemetrexed, when administered with folic acid and vitamin B12, has demonstrated comparable efficacy and a superior toxicity profile relative to docetaxel. A retrospective analysis of the Phase III trial of pemetrexed versus docetaxel shows a statistically significant longer toxicity-free survival time for pemetrexed compared with docetaxel. Newer targeted therapies, especially the epidermal growth factor receptor inhibitors gefitinib and erlotinib, have produced conflicting results and have only been compared with best supportive care and placebo. They should be compared directly to pemetrexed as second-line therapy in large, randomised studies of patients with advanced NSCLC. For patients with advanced recurrent NSCLC and good performance status who progress after first-line chemotherapy, pemetrexed should be considered as a new standard of care.