Pemetrexed

Overview
Pemetrexed (brand name Alimta®) is a chemotherapy drug manufactured and marketed by Eli Lilly and Company. Its indications are the treatment of pleural mesothelioma as well as non-small cell lung cancer.

History
The molecular structure of pemetrexed was developed by Edward C. Taylor at Princeton University and clinically developed by Indianapolis based drug maker, Eli Lilly and Company.

Mechanism of action
Pemetrexed is chemically similar to folic acid and is in the class of chemotherapy drugs called folate antimetabolites. It works by inhibiting three enzymes used in purine and pyrimidine synthesis&mdash;thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyl transferase (GARFT). By inhibiting the formation of precursor purine and pyrimidine nucleotides, pemetrexed prevents the formation of DNA and RNA, which are required for the growth and survival of both normal cells and cancer cells.

Clinical use
In February 2004, the Food and Drug Administration approved pemetrexed for treatment of malignant pleural mesothelioma, a type of tumor of the lining of the lung, in combination with cisplatin. In July 2004, the FDA granted approval as a second-line agent for the treatment of non-small cell lung cancer. Trials are currently testing it against esophagus and other cancers.

Patients are required to be on folic acid and vitamin B12 supplementation when they are on pemetrexed therapy. (In clinical trials for mesothelioma, folic acid and B12 supplementation reduced the frequency of adverse events.) It is also recommended for patients to be on a steroid (e.g. dexamethasone 4mg twice daily) on the day prior, day of, and day after pemetrexed infusion to avoid skin rashes.