Possible Interaction: Fluorouracil and Folate

“Extracellular reduced folate concentrations of 1 microM have been reported to yield maximal enzyme inhibition in several cell lines treated with 5-FU in vitro.”

“Various approaches have been used to improve the efficacy of 5-FU including inhibition of its degradation enzyme dihydropyrimidine dehydrogenase (DPD) such as S1, UTF, use of 5-FU pro-drug capecitabine to exploit thymidine phosphorylase (TP) and supplementation of reduced folate acid to increase cytotoxicity.”

“A maximum potentiation of growth inhibition (10-fold) occurred after combinations of FUra with excess folates and dIno.”

“ 5-FU targets folate metabolism through inhibition of thymidylate synthase (TYMS).”

“A polymorphism that may influence the efficacy of 5-FU by influencing folate pools is that of the methylenetetrahydrofolate reductase(MTHFR)gene.”

“Finally, gastric cancer patients received CDDP, epirubicin, 5-FU and FA or weekly 5-FU plus FA.”

“This phenomenon should be avoided when 5-fluorouracil is used with reduced folate in cancer chemotherapy.”

“In oncology combining folates with 5-fluorouracil (5-FU) enhances the cytotoxic effects of chemotherapy in colon cancer patients.”

“The reduced folate , leucovorin, has been shown to enhance the activity of 5-FU in colorectal cancer.”

“Recently, preclinical studies have shown that the antitumor activity of FUra can be potentiated by modulating the metabolism of this drug by using other substances, in particular antifolates of folates.”