Effect of intraperitoneal administration of docetaxel on peritoneal dissemination of gastric cancer.
The effect of intraperitoneal (i.p.) administration of docetaxel was evaluated for preclinical evidence of anticancer activity in athymic mice bearing 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 i.p. with 10(7) MKN-45-P cells. On days 2, 5, 9, 12, 16 and 19 after tumor inoculation, mice were treated with i.p. injection of docetaxel. Treatment doses of docetaxel were 8 mg/kg (N = 7) 2 mg/kg (N = 7) and 0.5 mg/kg (N = 7). Intraperitoneal carcinoembryonic antigen (CEA) levels, animal body weight, mortality and survival were determined. All control mice developed ascites and died within 19-40 days. The median survival time in the control group was 32 days, while those of mice treated with 8, 2 and 0.5 mg/kg were 90, 63 and 49.5 days, respectively. One of seven mice treated with 8 mg/kg of docetaxel died of toxicity on day 12. Four mice were tumor-free on day 90, but two had tumors in the abdomen when autopsied on day 90. One mouse treated with 2 mg/kg was ascertained to be tumor-free on day 90. All seven mice treated with 0.5 mg/kg of docetaxel died of peritoneal dissemination within 71 days. The results suggest the potential of intraperitoneal docetaxel administration for the treatment of peritoneal dissemination of gastric cancer.
Yonemura
Yutaka
Y
Peritoneal Dissemination Program, Shizuoka Cancer Center, 1007 Shimo-nagakubo, Nagaizumi-machi, Suntou-gun, Shizuoka 411-8777, Japan. y.yonemura@scchr.jp
Endou
Yoshio
Y
Bando
Etsurou
E
Kuno
Kiyoshi
K
Kawamura
Taiichi
T
Kimura
Masashi
M
Shimada
Tsutomu
T
Miyamoto
Ken-Ichi
K
Sasaki
Takuma
T
Sugarbaker
Paul H
PH
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000494:pharmacology*; D002272:Carcinoembryonic Antigen / Q000032:analysis; D000077143:Docetaxel; D005260:Female; D007263:Infusions, Parenteral; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000556:secondary* / Q000662:veterinary; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D016019:Survival Analysis; D043823:Taxoids / Q000008:administration & dosage* / Q000494:pharmacology*
D000972:Antineoplastic Agents, Phytogenic; D002272:Carcinoembryonic Antigen; D043823:Taxoids; D000077143:Docetaxel