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.
Fossella
Frank V
FV
Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D005971:Glutamates / Q000009:adverse effects / Q000627:therapeutic use*; D006147:Guanine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D000068437:Pemetrexed; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D005971:Glutamates; D000068437:Pemetrexed; D006147:Guanine