[Thymidylate synthase inhibition in malignant tumors after oral administration of UFT]

Surgical resection of solid tumors was undertaken five to six hours after the oral administration of UFT (300-500 mg/body) in five patients, who were (then) assayed for 5-fluorodeoxyuridylate (FdUMP), total dTMP synthase (TS) and non-FdUMP-bound, free enzyme. Three patients had gastric cancer, and two had mammary cancer. Control solid tumors were obtained without, the drug in eight patients. Six patients had gastric cancer. Eight had mammary cancer. Total TS averaged 2.04 p mol/g in the malignant tissues. TS inhibition averaged 40.1% to 57.1% in gastric cancer and 17.1% to 52.7% in mammary cancer. These data suggest that TS inhibition after oral administration of 5FU derivatives may be usefully studied for biochemical parameters of mechanisms of drug resistance.