title: Pemetrexed (ALIMTA), a novel multitargeted antineoplastic agent.
abstract: Pemetrexed (ALIMTA, LY231514, MTA) is a novel antimetabolite that inhibits at least three enzymes involved in the folate pathway. These enzymes are thymidylate synthase, dihydrofolate reductase, and glycinamide ribonucleotide formyltransferase. Pemetrexed has demonstrated clinical activity in non-small cell lung cancer as well as in a broad array of other solid tumors, including mesothelioma, breast, colorectal, bladder, cervical, gastric and pancreatic cancer. In non-small cell lung cancer, single-agent activity has been documented in the first- and second-line settings in Phase II and Phase III trials. Promising activity has also been demonstrated when pemetrexed is combined with platinum compounds (cisplatin, carboplatin, and oxaliplatin), vinorelbine, and gemcitabine. Low level dietary supplement of folic acid and vitamin B12 has significantly decreased the mucosal and bone marrow toxicity of pemetrexed without compromising its antitumor effect.
authors.affiliation: Mayo Clinic and Foundation, Departments of Oncology, Rochester, Minnesota, USA. adjei.alex@mayo.edu
authors.forename: Alex A
authors.initials: AA
authors.lastname: Adjei
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D005492:Folic Acid / Q000008:administration & dosage; D005971:Glutamates / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D006147:Guanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D009369:Neoplasms / Q000188:drug therapy; D000068437:Pemetrexed; D017671:Platinum Compounds / Q000627:therapeutic use; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors; D014805:Vitamin B 12 / Q000008:administration & dosage
chemical_list: D000970:Antineoplastic Agents; D005971:Glutamates; D017671:Platinum Compounds; D000068437:Pemetrexed; D006147:Guanine; D005492:Folic Acid; D013940:Thymidylate Synthase; D014805:Vitamin B 12