Pemetrexed for treatment of advanced non-small cell lung cancer

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. © 2004 Elsevier Inc. All rights reserved.