[Effect of intraperitoneal chemotherapy on experimental peritoneal dissemination of gastric cancer].
In vitro chemosensitivity test using a collagen-gel method was done on 165 primary gastric cancers. All of 5-FU, CBDCA, CDDP and docetaxel showed a high sensitivity. The effects of per oral (po) administration of TS-1, a combination of po TS-1 and intraperitoneal (ip) administration of CDDP, ip 5-FU and ip docetaxel, were evaluated in athymic mice bearing peritoneal dissemination of a gastric cancer cell line (MKN-45-P that shows a high rate of metastasis to the peritoneal cavity of nude mice). Nude mice were inoculated by ip with 10(7) MKN-45-P cells. No survival benefit was obtained after po administration of TS-1 (12 mg/kg) alone or ip CDDP alone. However, a combination of po TS-1 (8 mg/kg x 10 days, from day 3) and ip CDDP (3.5 mg/kg, day 6 and 13) showed a significant survival improvement than that of po TS-1 or ip CDDP treatment alone. ip administration of 30 mg/kg (3 times/week x 3 weeks) or 15 mg/kg (6 times/week x 3 weeks) of 5-FU significantly improved the survival of mice bearing MKN-45-P. 5-FU concentration of ascites after ip administration of 30 mg/kg of 5-FU was 600-fold higher than po administration of 12 mg/kg of TS-1 at peak level. ip injections of docetaxel of 8 mg/kg, and 2 mg/kg improved the survival of 4 and 1 mice, respectively, and they were tumor-free on day 90. Survival of mice treated with ip injection of CBDCA (100 mg/kg, on day 3, or 50 mg/ kg on day 3 and 10) was significantly better than the control group. These results suggest the potential of po TS-1 + ip CDDP, ip 5-FU, ip docetaxel and ip CBDCA administration for the treatment of peritoneal dissemination of gastric cancer.
Yonemura
Yutaka
Y
Peritoneal Dissemination Program, Shizuoka Cancer Center, Kanazawa University Hospital.
Endou
Yoshio
Y
Tochiori
Shizuka
S
Bando
Etsurou
E
Kawamura
Taiichi
T
Shimada
Tsutomu
T
Miyamoto
Ken-ichi
K
Tanaka
Motohiro
M
Sasaki
Takuma
T
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D016190:Carboplatin / Q000008:administration & dosage; D002945:Cisplatin / Q000008:administration & dosage; D000077143:Docetaxel; D004338:Drug Combinations; D004354:Drug Screening Assays, Antitumor; D005472:Fluorouracil / Q000008:administration & dosage; D007263:Infusions, Parenteral; D051379:Mice; D008819:Mice, Nude; D009366:Neoplasm Seeding; D010094:Oxonic Acid / Q000008:administration & dosage; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000556:secondary*; D011725:Pyridines / Q000008:administration & dosage; D013274:Stomach Neoplasms / Q000473:pathology*; D043823:Taxoids / Q000008:administration & dosage; D005641:Tegafur / Q000008:administration & dosage
D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D004338:Drug Combinations; D011725:Pyridines; D043823:Taxoids; C079198:S 1 (combination); D005641:Tegafur; D000077143:Docetaxel; D010094:Oxonic Acid; D016190:Carboplatin; D002945:Cisplatin; D005472:Fluorouracil