Pemetrexed: a novel antifolate agent enters clinical practice.
Pemetrexed (Alimta, Eli Lilly) is a multitargeted antifolate that inhibits at least three enzymes in the nucleic acid synthetic pathways. The US Food and Drug Administration recently approved pemetrexed, in combination with cisplatin, for the first-line treatment of advanced malignant pleural mesothelioma. Moreover, pemetrexed was recently shown to be as efficacious as docetaxel (Taxotere, Aventis) in the second-line treatment of non-small cell lung cancer, and its toxicity profile was preferable. The main toxicity seen with pemetrexed is myelosuppression, which is considerably reduced by coadministration of folic acid and vitamin B12. Multiple Phase II clinical trials have demonstrated that pemetrexed has promising single-agent activity in many other solid tumors, including head and neck, breast and colorectal cancers. Combination regimens consisting of pemetrexed and other chemotherapeutics or novel molecular-targeted agents are currently under investigation. Future studies will better define and likely expand the role of pemetrexed for the treatment of cancer.
Department of Medicine, Division of Hematology/Oncology, The Feinberg School of Medicine, Robert H Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL 60611, USA.
Victoria
V
Kut
Jyoti D
JD
Patel
Athanassios
A
Argiris
D000964:Antimetabolites, Antineoplastic / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D000077143:Docetaxel; D005971:Glutamates / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*; D006147:Guanine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D000068437:Pemetrexed; D043823:Taxoids / Q000008:administration & dosage
D000964:Antimetabolites, Antineoplastic; D005971:Glutamates; D043823:Taxoids; D000068437:Pemetrexed; D000077143:Docetaxel; D006147:Guanine; D002945:Cisplatin