BACKGROUND: Favorable results have been reported for the novel oral anticancer agent S-1 (TS-1) in clinical studies of advanced gastric cancer with peritoneal dissemination. In the present study we assessed its pharmacokinetics, inhibitory effects, and effect on survival time in an animal model. METHODS: A model of peritoneal dissemination was created by intraperitoneally implanting 4-week-old female BALBc nu/nu mice with the human gastric cancer cell line MKN-45 after transfection with a fluorescent protein-expressing vector. Pharmacokinetics were investigated by measuring intratumor, peritoneal lining, and blood concentrations after the administration of S-1 and fluorouracil (5-FU). The effect of S-1 on survival time was also assessed, by administration once daily to seven animals per group, starting on day 7 after implantation, and survival time was compared with that of an untreated control group. The inhibitory effect of S-1 on peritoneal dissemination was evaluated by killing mice at the start of administration, and 1 and 3 weeks after the start of administration, and examining them for the presence of peritoneal dissemination under a fluorescence stereomicroscope. RESULTS: Maintenance of high 5-FU concentrations in the intraperitoneal tumors was confirmed in the S-1 group, and survival time was prolonged without any decrease in oral food intake or body weight. CONCLUSION: Assessment in a model of peritoneal dissemination of gastric cancer showed that the novel oral anticancer agent S-1 was effective against peritoneal dissemination, and that it improved the survival rate.
BACKGROUND: Favorable results have been reported for the novel oral anticancer agent S-1 (TS-1) in clinical studies of advanced gastric cancer with peritoneal dissemination. In the present study we assessed its pharmacokinetics, inhibitory effects, and effect on survival time in an animal model. METHODS: A model of peritoneal dissemination was created by intraperitoneally implanting 4-week-old female BALBc nu/nu mice with the humangastric cancer cell line MKN-45 after transfection with a fluorescent protein-expressing vector. Pharmacokinetics were investigated by measuring intratumor, peritoneal lining, and blood concentrations after the administration of S-1 and fluorouracil (5-FU). The effect of S-1 on survival time was also assessed, by administration once daily to seven animals per group, starting on day 7 after implantation, and survival time was compared with that of an untreated control group. The inhibitory effect of S-1 on peritoneal dissemination was evaluated by killing mice at the start of administration, and 1 and 3 weeks after the start of administration, and examining them for the presence of peritoneal dissemination under a fluorescence stereomicroscope. RESULTS: Maintenance of high 5-FU concentrations in the intraperitoneal tumors was confirmed in the S-1 group, and survival time was prolonged without any decrease in oral food intake or body weight. CONCLUSION: Assessment in a model of peritoneal dissemination of gastric cancer showed that the novel oral anticancer agent S-1 was effective against peritoneal dissemination, and that it improved the survival rate.
Authors: Y Yonemura; T Fujimura; S Fushida; H Fujita; E Bando; G Nishimura; K Miwa; Y Endou; M Tanaka; T Sasaki Journal: Hepatogastroenterology Date: 1999 Jan-Feb
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