The purposes of this study were to evaluate the antitumor activity of S-1 (1 M
tegafur, 0.4 M 5-chloro-2,4-dihydroxypyridine and 1 M
potassium oxonate) on human lung
tumor xenografts, as compared with other fluoro-
pyrimidines, and to investigate the relationships between fluoropyrimidine antitumor activities and four distinct enzymatic activities involved in the phosphorylation and degradation pathways of
5-fluorouracil (5-FU) metabolism. S-1, UFT (1 M
tegafur-4 M
uracil),
5'-deoxy-5-fluorouridine (5'-DFUR),
capecitabine and
5-FU were administered for 14 consecutive days to nude mice bearing lung
tumor xenografts. S-1 showed stronger
tumor growth inhibition in four of the seven
tumors than the other drugs. Cluster analysis, on the basis of antitumor activity, indicated that S-
1/UFT and 5'-DFUR/
capecitabine/5-FU could be classified into another group. We investigated
tumor thymidylate synthase content,
dihydropyrimidine dehydrogenase (DPD) activity,
thymidine phosphorylase (TP) activity and orotate phosphoribosyl
transferase activity in seven human lung
tumor xenografts and performed regression analyses for the antitumor activities of fluoropyrimidines. There were inverse correlations between antitumor and DPD activities for
5'-DFUR (r=-0.79, P=0.034),
capecitabine (r=-0.56, P=0.19) and
5-FU (r=-0.86, P=0.013). However, no such correlations were observed for S-1 and UFT. These findings suggest that S-1 containing a potent DPD inhibitor may have an antitumor effect on lung
tumors, with high basal DPD activity, superior to those of other fluoropyrimidines.