The chemosensitivity of
micrometastases in the peritoneal cavity to a
5-fluorouracil derivative (TS-1) was examined with a
micrometastasis model featuring a human
gastric cancer cell line tagged with the green fluorescence
protein (GFP) gene in nude mice. Peritoneal
metastases on the omentum and mesentery could be specifically visualized even when minute or dormant and also externally monitored noninvasively under illumination with blue light from 1 day after intraperitoneal (i.p.) injection of
tumor cells. Metastatic deposits formed after i.p. injection of 2x10(6)
tumor cells were significantly reduced by
TS-1 in a dose-dependent manner (15-20 mg/kg), when it was orally administered from day 1 post-injection for 4 weeks (early administration). No such inhibition was evident after injection of 1x10(7)
tumor cells. When 2x10(6)
tumor cells given injection, the
ascites-free period in TS-1-treated mice was significantly longer than in their untreated counterparts. Survival of TS-1-treated mice (5/15) was also significantly higher than the zero rate in controls (0/15), with 4 out of 5 surviving mice being free from peritoneal
metastasis and the exception having only a few dormant
metastases. In contrast, when
TS-1 was administered starting from day 7 post-injection for 4 weeks (late administration), the survival and
ascites-free period of the TS-1-treated mice were not significantly influenced. The results indicate that the chemosensitivity of peritoneal
metastases to
TS-1 is dependent on the number of i.p.
tumor cells and the timing of
drug administration. Peritoneal
micrometastases at an early stage are most susceptible and can be effectively eliminated by
oral administration of an anti-
cancer agent, which leads to the longer survival and better quality of life (QOL) of the mice.