Therapeutic Effect of 1 M Tegafur‐0.4 M 5‐Chloro‐2,4‐dihydroxypyridine‐1 M Potassium Oxonate (S‐1) on Liver Metastasis of Xenotransplanted Human Colon Carcinoma

S‐1 [1 M tegafur (FT)‐0.4 M 5‐chloro‐2,4‐dihydroxypyridine (CDHP)‐1 M potassium oxonate (Oxo)], was developed as a new oral antineoplastic agent based on biochemical modulation of fluorouracil (5‐FU) by CDHP and Oxo. The therapeutic effect of S‐1 on human colon cancer xenografts (TK‐13) with high metastatic potential to the liver was evaluated. Small pieces of TK‐13 were sutured into the cecal wall of 52 nude mice, and the animals were randomly divided into 3 groups [control (n=17), UFT (combination of 1 M FT and 4 M uracil) (n=18) and S‐1 (n=17)]. S‐1 or UFT was administered orally at an equitoxic dose (S‐1, 7.5 mg/kg; UFT, 17.5 mg/kg as FT) for 37 consecutive days beginning 10 days after the transplantation. S‐1 showed higher tumor growth inhibition than UFT (P < 0.05) and also showed a significant anti‐metastatic effect on liver metastasis, while UFT did not. Liver metastasis developed in only 2 of the 17 mice (12%) in the S‐1 group, whereas it developed in 9 of the 17 (53%) and 7 of the 18 (39%) in the control and UFT group, respectively. Analysis of AUC (area under the curve) revealed that S‐1 yielded higher 5‐FU levels in both tumor tissue (1.6 times) and plasma (2.5 times) than UFT. These results suggest that S‐1 will show a higher clinical therapeutic effect against human colorectal cancer than UFT.