Dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine S-1 may be effective against peritoneal dissemination in gastric cancer.
The effects of a novel oral fluoropyrimidine derivative S-1 on peritoneal metastasis from gastric cancer were investigated. OCUM-2MD3 cells, a highly peritoneal-metastatic cell line, were injected intraperitoneally in nude mice. These mice were allocated to the following three groups (each group, n=10): the S-1 group, to which 10 mg/kg body weight of S-1 was administered per os daily; the FT group, to which 100 mg/kg body weight of tegafur (FT) was administered per os daily; the control group, to which no anticancer drug was administered. Drug administration was starting the day after inoculation. The median survival time of the S-1 group was found to be significantly longer than that of the FT group (30 days vs. 23 days; P<0.005) and the control group (vs. 24 days; P<0.005). The mean values of 5-fluorouracil (5-FU) concentrations in ascites of the S-1 group at 1-4 h were 414-580 ng/ml (n=5), and those of FT group were 70-87 ng/ml (n=5), with significant differences between the two groups at each observation time. The high CDHP concentrations in ascites of the S-1 group were observed at 1-6 h after drug administration. DPD was expressed strongly in fibrous tissue around peritoneal metastasis and weakly in tumor cells of peritoneal metastasis themselves. The high concentrations and long duration of 5-FU in the peritoneal cavity after S-1 administration suggest that S-1 may be effective against peritoneal dissemination. High concentrations of CDHP may prevent 5-FU degradation in peritoneal dissemination and its surrounding fibrous tissue.
Yamagata
Shigehito
S
Department of Surgical Oncology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan.
Nakata
Bunzo
B
Hirakawa
Kosei
K
D000284:Administration, Oral; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D001201:Ascites / Q000378:metabolism; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000037:antagonists & inhibitors*; D004338:Drug Combinations; D005260:Female; D005472:Fluorouracil / Q000378:metabolism; D007274:Injections, Intraperitoneal; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010094:Oxonic Acid / Q000008:administration & dosage*; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000556:secondary; D011725:Pyridines / Q000008:administration & dosage*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D015996:Survival Rate; D005641:Tegafur / Q000008:administration & dosage*; D014407:Tumor Cells, Cultured
D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; D011725:Pyridines; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D042943:Dihydrouracil Dehydrogenase (NADP); D005472:Fluorouracil