Pemetrexed disodium: a novel antifolate clinically active against multiple solid tumors.
Article Details
- CitationCopy to clipboard
Hanauske AR, Chen V, Paoletti P, Niyikiza C
Pemetrexed disodium: a novel antifolate clinically active against multiple solid tumors.
Oncologist. 2001;6(4):363-73.
- PubMed ID
- 11524555 [ View in PubMed]
- Abstract
Pemetrexed disodium (ALIMTA), "pemetrexed") is a novel, multi-targeted antifolate that has demonstrated promising clinical activity in a wide variety of solid tumors, including non-small cell lung, breast, mesothelioma, colorectal, pancreatic, gastric, bladder, cervix, and head and neck. Pemetrexed inhibits multiple folate-dependent enzymes involved in both purine and pyrimidine synthesis including thymidylate synthase, dihydrofolate reductase, glycinamide ribonucleotide formyltransferase, and aminoimidazole carboxamide ribonucleotide formyltransferase. As a single agent, pemetrexed exhibits a moderate toxicity profile at a dose of 500 mg/m(2) by 10-minute infusion once every 21 days with myelosuppression being the dose-limiting toxicity. Folic acid added to the diet in preclinical studies reduced toxicities while maintaining antitumor activity. Based on this observation and clinical toxicities, folic acid and vitamin B(12) dietary supplementation has been recently introduced into all ongoing trials. Studies combining pemetrexed with other active chemotherapeutic agents demonstrate that these combination therapies may become important treatment regimens in a variety of cancer types. Currently, pemetrexed phase III trials are ongoing in mesothelioma and non-small cell lung cancer with future trials planned to explore this unique multitargeted antifolate.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Pemetrexed Bifunctional purine biosynthesis protein PURH Protein Humans YesInhibitorDetails Pemetrexed Dihydrofolate reductase Protein Humans YesInhibitorDetails Pemetrexed Thymidylate synthase Protein Humans YesInhibitorDetails Pemetrexed Trifunctional purine biosynthetic protein adenosine-3 Protein Humans YesInhibitorDetails