Another oral agent is a combination of uracil and the fluoruracil prodrug tegafur. Uracil is a competitive inhibitor of dihydropyrimidine dehydrogenase that is the rate-limiting enzyme in the catabolism of FU. UFT has been studied in combination with oral leu-covorin.
A total of 380 patients were randomised to receive either UFT (300 mg/m2/day) and LV (90 mg/day), administered for 28 days every 35 days, or FU (425 g/m2/day) and LV (20 mg/m2/day), given IV for 5 days every 35 days. There were no statistically significant differences in survival, tumour response, duration of response and time to response. Substantial safety benefits were observed in patients treated with UFT-LV .
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