Pemetrexed A potential new therapeutic option for the treatment of Thymidylate Synthase


Lyndon Kim, MD, Kevin Judy, MD, James Evans, MD, Christopher Farrell, MD, and David Andrews, MD


  • Fluoropyrimidine analogues, 5FU, Capecitabine and Pemetrexate, inhibit thymidylate synthase and they have been widely used for the treatment of systemic malignancies.
  • Capecitabine can penetrate CNS and has shown some efficacy in the treatment of breast cancers with CNS metastasis. However, the role of Pemetrexed in the treatment of recurrent primary and systemic malignancies with CNS metastasis is not known.
  • Pemetrexed is a multitargeted antifolate drug similar to methotrexate, but, unlike methotrexate, has the advantage of targeting more than 1 site in folate metabolism. It inhibits three enzymes used in purine and pyrimidine synthesis – Thymidine Synthetase (TS), Dihydrofolate reductase, and glycinamide ribonucleotide.
  • We have treated 34 patients (pts) with previously heavily-treated recurrent primary and systemic malignancies with CNS metastasis based on the results of the molecular profiling.
  • 17/34 pts were found to have TS Deficiency and 10/17 TS Deficient pts were treated with Pemetrexed.

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