5-fluorouracil and uft-sensitive gastric carcinoma has a high level of thymidylate synthase

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Abstract
The authors examined the relationship between the level of thymidylate synthase (TS) and the sensitivity to 5‐fluorouracil (5‐FU) and UFT, a combined oral preparation of 1‐(2‐tetrahydrofuryl)‐5‐fluorouracil (tegafur) and uracil in a molar ratio of 1:4. For the studies we used the subrenal capsule (SRC) assay and 15 human gastric cancer tissues. The TS levels were assayed by the ligand‐binding technique, using [6–3H]FdUMP. The relative variation of tumor size (ΔTuS/TuS0) was calculated to be as follows: ΔTuS/TuS0 = [(TuS6 – TuS0/TuS0] X 100 (%), where TuS6 was the tumor size on day 6 and TuS0 on day 0. The chemosensitivity was considered to be positive when ΔTuS/TuS0 in the treated group decreased to below –10%. Decrease in tumor size was marked in case of exposure to UFT (‐19.8 ± 13.0%) (mean ± standard deviation), compared with that to 5‐FU (‐9.0 ± 7.2%), with a statistically significant difference (P < 0.001). The TS level varied from 1.7 to 30.8 pmol/g gastric cancer tissue and the mean was 7.1 ± 7.2 pmol/g tissue. A correlation was noted between the TS level and decrease in size of the tumor exposed to 5‐FU (r = −0.671) or UFT (r = −0.758): gastric cancer tissue with higher level of TS is more sensitive to 5‐FU and UFT than is that with a lower TS level. These findings show that the sensitivity to 5‐FU and UFT of gastric cancer tissue is related to the TS level and that UFT shows promise for the treatment of patients with gastric cancer.