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The antitumor activity of 1-(2-tetrahydrofuryl)-5-fluorouracil (FT-207) on sarcoma was enhanced by oral coadministration of uracil, thymine, or thymidine. The activity was enhanced equally by thymine and by uracil than by thymidine, but thymine caused loss in body weight. The antitumor activity of 5-fluorouracil (5-FU) was also enhanced by thymine or uracil, but both caused loss in body weight. Degradation of 5-FU in vitro was inhibited more by thymine than by uracil. Phosphorylation of 5-FU, however, was not inhibited by uracil, thymine, or thymidine, even at 100 times the concentration of 5-FU. These results suggest that the mechanism of enhancement of the antitumor activity of FT-207 by thymine or thymidine was similar to that by uracil, and that uracil had more effect than thymine or thymidine in enhancing antitumor effect of these drugs to FT-207 without toxicity.
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