Anticancer activity and toxicity of S-1, an oral combination of tegafur and two biochemical modulators, compared with continuous iv infusion of 5-fluorouracil
Anticancer activity and toxicity of S-1, an oral combination of tegafur and two biochemical modulators, compared with continuous iv infusion of 5-fluorouracil
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DOI：
10.1097/00001813-199810000-00012
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发表时间：
1998-10-01
影响因子：
2.3
通讯作者：
Shirasaka, T
中科院分区：
文献类型：
--
作者：
Fukushima, M;Shimamoto, Y;Shirasaka, T
S-1是1 M替加氟[5-氟尿嘧啶（5-FU）的前药]、0.4 M 5-氯-2，4-二羟基吡啶（二氢嘧啶脱氢酶的可逆性抑制剂）和1 M oxonate钾（乳清酸磷酸核糖基转移酶的抑制剂）的口服复方制剂。在实验性肿瘤模型中，S-1显示出强的抗肿瘤作用，胃肠道毒性低。因此，我们比较了口服S-1与持续输注5-FU在人和小鼠肿瘤移植大鼠中的抗肿瘤作用。通过连续给予30 mg/kg/天经口S-1和40 mg/kg/天输注5-FU，在7天时间表中，荷Yoshida肉瘤大鼠的肿瘤生长几乎完全抑制。然而，观察到S-1和5-FU的毒性发生率之间存在显著差异，包括体重减轻和腹泻。输注5-FU的大鼠体重明显减轻，腹泻严重，而口服S-1的大鼠两者都没有。在裸鼠移植人结肠癌（KM 12 C）模型中，口服S-1 15 mg/kg/d和输注5-FU 30 mg/kg/d，肿瘤生长抑制率约为50%，但5-FU治疗组的体重减轻率明显高于S-1治疗组。胃肠道组织中5-氟尿嘧啶浓度与肿瘤中浓度的比值在S-1处理的大鼠中低于5-FU处理的大鼠。总之，结果表明，从抗肿瘤效力和毒性的角度来看，口服S-1可能比持续输注5-FU更有效地治疗癌症患者。[(C)1998 Lippincott威廉姆斯& Wilkins.]。
S-1 is an oral combined form of 1 M tegafur [a prodrug of 5-fluorouracil (5-FU)], 0.4 M 5-chloro-2,4-dihydroxypyridine (a reversible inhibitor of dihydropyrimidine dehydrogenase) and 1 M potassium oxonate (an inhibitor of orotate phosphoribosyltransferase). S-1 has been shown to exert a potent antitumor effect with low gastrointestinal toxicity in experimental tumor models, We have therefore compared the antitumor effect of oral S-1 with that of continuous infusion of 5-FU in rats bearing transplants of human and murine tumors. Almost complete inhibition of the tumor growth was obtained on 7 day schedules in Yoshida sarcoma-bearing rats by consecutive administration of 30 mg/kg/day of oral S-1 and 40 mg/kg/day infusion of 5-FU. However, a significant difference between the incidence of toxicities of S-1 and 5-FU, including body weight loss and diarrhea, was noted. The rats given the 5-FU infusion had marked weight loss and severe diarrhea, while those given oral S-1 had neither. Although about 50% inhibition of the tumor growth was attained with 15 mg/kg/day of oral S-1 and 30 mg/kg/day infusion of 5-FU in nude rats with xenografted human colon cancer (KM12C), the rate of body weight loss in the 5-FU-treated group was distinctly higher than in the S-1-treated group. The ratio of the 5-fluoronucleotide concentrations in gastrointestinal tissue to that in the tumor was lower in the S-1-treated rats than in the 5-FU-treated rats. In conclusion, the results suggest that oral S-1 might be more effective in the treatment of cancer patients than continuous infusion of 5-FU, from the standpoint of antitumor potency and toxicity. [(C) 1998 Lippincott Williams & Wilkins.].