Pemetrexed for treatment of advanced non-small cell lung cancer.

Abstract

The novel antifolate pemetrexed targets multiple enzymes involved in folate metabolism, resulting in inhibition of DNA synthesis. Pemetrexed has shown antitumor activity in preclinical models against a variety of tumor types, including non-small cell lung cancer. Phase II studies have confirmed its single-agent activity and manageable toxicity profile, and pemetrexed has shown antitumor activity in combination with other chemotherapeutics, including gemcitabine, taxanes, platinums, and vinorelbine, in the first-line treatment of advanced non-small cell lung cancer. A large ongoing phase III trial is comparing the activity of pemetrexed versus docetaxel in the second-line setting. Supplementation with oral folic acid and vitamin B12 was shown to reduce pemetrexed-related toxicity and increase its therapeutic index. These data suggest that pemetrexed has significant activity in advanced non-small cell lung cancer and represents a new treatment option for patients with this disease.