Pemetrexed and its emerging role in the treatment of thoracic malignancies.
Pemetrexed (Alimta); Eli Lilly and Co., Indianapolis, IN, USA) is a unique multitargeted antifolate that inhibits at least three enzymes, thymidylate synthase, dihydrofolate reductase and glycinamide ribonucleotide formyltransferase. This novel drug is being evaluated in a comprehensive clinical programme for use in both front-line and second-line therapies. It has shown broad activity in a number of solid tumours, including colon cancer, breast cancer, lung cancer, head and neck, cervical cancer and others. While a number of antifolates have been evaluated in clinical trials, further development has been stopped or delayed by the occurrence of life-threatening toxicities. Similar trends were also initially observed with pemetrexed as well, but investigators later showed that these toxicities could be minimised with folic acid and vitamin B(12) supplementation included in the treatment regimen. Preliminary data indicate that this supplementation does not hamper drug efficacy in most tumour types and in many cases, supplemented patients exhibit improved clinical outcome. Here, the current data for pemetrexed in treating thoracic malignancies are reviewed, with special focus on malignant pleural mesothelioma and non-small cell lung cancer.
University of Torino, Department of Clinical & Biological Sciences, S. Luigi Hospital-Thoracic Oncology Unit, Regione Gonzole 10-10043 Orbassano, Turin, Italy. scagliotti@ihnet.it
Giorgio V
GV
Scagliotti
Silvia
S
Novello
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy; D002986:Clinical Trials as Topic; D005493:Folic Acid Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D005971:Glutamates / Q000008:administration & dosage / Q000627:therapeutic use*; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy; D008654:Mesothelioma / Q000188:drug therapy; D000068437:Pemetrexed; D010997:Pleural Neoplasms / Q000188:drug therapy; D013899:Thoracic Neoplasms / Q000188:drug therapy*; D014815:Vitamins / Q000627:therapeutic use
D000970:Antineoplastic Agents; D005493:Folic Acid Antagonists; D005971:Glutamates; D014815:Vitamins; D000068437:Pemetrexed; D006147:Guanine