Experimental study to evaluate the usefulness of S-1 in a model of peritoneal dissemination of gastric cancer.
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.


CONCLUSIONS
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.
Mori
Takuji
T
Department of Surgery and Clinical Oncology, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka (E-2), Suita, Osaka 565-0871, Japan.
Fujiwara
Yoshiyuki
Y
Yano
Masahiko
M
Tamura
Shigeyuki
S
Yasuda
Takushi
T
Takiguchi
Shuji
S
Monden
Morito
M
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D001835:Body Weight; D004195:Disease Models, Animal; D004338:Drug Combinations; D004435:Eating; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology; D007564:Japan; D020714:Maximum Tolerated Dose; D051379:Mice; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence; D010094:Oxonic Acid / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D010534:Peritoneal Neoplasms / Q000556:secondary*; D011725:Pyridines / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000473:pathology*; D016019:Survival Analysis; D005641:Tegafur / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D013997:Time Factors
D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; D011725:Pyridines; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D005472:Fluorouracil