Pemetrexed (
ALIMTA,
LY231514) is a novel, multi targeted
antifolate chemotherapy agent that is active in various
tumors including
mesothelioma, NSCLC, breast, colon and bladder
carcinoma.
Pemetrexed inhibits several
enzymes in the
folate pathway including
thymidylate synthase, dihydrofolate reductase, and
glycinamide ribonucleotide formyltransferase.
Pemetrexed is approved in the United States and a number of European Union countries for use in the treatment of
mesothelioma, and the second-line treatment of advanced NSCLC. However, in Japan,
pemetrexed was approved for use only in combination with
cisplatin in the treatment of
mesothelioma in January 2007. This approval was granted on the basis of a phase III trial of
pemetrexed in combination with
cisplatin versus
cisplatin alone in patients with
malignant pleural mesothelioma. Treatment with
pemetrexed plus
cisplatin and
vitamin supplementation, resulted in superior survival time, time to progression, and response rates compared with treatment with
cisplatin alone. In addition, in a phase III trial of
pemetrexed versus
docetaxel in patients with NSCLC previously treated with
chemotherapy, treatment with
pemetrexed resulted in clinically equivalent efficacy outcomes, but with significantly fewer side effects including grade 3 or 4
neutropenia , neutropenic
fever, and
alopecia, compared with
docetaxel. Therefore,
pemetrexed should be considered a standard treatment option for second-line NSCLC in US and most of EU. Addition of
folic acid and
vitamin B12 significantly reduced the toxicity of
pemetrexed, especially hematologic toxicity and gastrointestinal toxicity.
Pemetrexed is the expected agent for use in high risk patients, especially elderly or poor performance status patients.