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.
Konno
H
H
Department of Surgery II, Hamamatsu University School of Medicine. hkonno@hama-med.ac.jp
Tanaka
T
T
Baba
M
M
Kanai
T
T
Matsumoto
K
K
Kamiya
K
K
Nakamura
S
S
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000601:surgery; D004338:Drug Combinations; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010094:Oxonic Acid / Q000627:therapeutic use*; D011725:Pyridines / Q000627:therapeutic use*; D005641:Tegafur / Q000627:therapeutic use*; D014183:Transplantation, Heterologous
D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; D011725:Pyridines; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid