Pemetrexed – Novel Antifolate Clinically Active against Multiple Solid Tumors

The following is an abstract taken form a report authored by Axel R. Hanauske, Victor Chen, Paolo Paoletti and Clet Niyikiza, published in The Oncologist September 2001 edition. Click on the link to the right of the screen to read the full article.

Pemetrexed disodium, (ALIMTA) is a novel, multi-targeted antifolate that has demonstrated promising clinical activity in a wide variety of solid tumours, including non-small cell lung, breast, mesothelioma, colorectal, pancreatic, gastric, bladder, cervix, and head and neck.

Pemetrexed inhibits multiple folate-dependant enzymes involved in both pruine and pyrimidine synthesis including thymidylate synthase, dihydrofolate reductase, glycinamide ribonucleotide formyltransferase and aminoimidazole carboxamide ribonucleotide formultransferase.

As a single agent, pemetrexed exhibits a moderate toxicity profile at a dose of 500 mg/m2 by 10 minute infusion once every 21 days with myelosupression being the dose-limiting toxicity. Folic acid added to the diet in preclinical studies reduced toxicities while maintaining antitumour activity. Based on this observation and clinical toxicities, folic acid and vitamin B12 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.

(Source: The Oncologist)