| 著者 |
米村, 豊
遠藤, 良夫
栃折, 静
坂東, 悦郎
川村, 泰一
嶋田, 努
宮本, 謙一
田中, 基弘
佐々木, 琢磨
|
|
内容記述 |
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.コラーゲンゲル法により原発胃癌の薬剤感受性を調べたところ, CBDCA, CDDP, 5-FU, docetaxel(DOC)が高い感受性を示した. 胃癌高度腹膜転移株MKN-45-PをTS-1(12mg/kg)で治療した群では, 治療開始日に関係なく対照群の生存率と差がなかった. 5-FU 15mg/kg ip, 18回, 30mg/kg ip, 9回投与群ではTS-1 12mg/kg po(計20回)や対照群に比べ有意に生存率がよかった. 5-FU 30mg/kg ip投与群の注入液の5-FU濃度は600μg/mlと高値を示した. TS-1 12mg/kg投与60分での腹水中5-FU, CDHP濃度は927±558ng/ml, 1,483±719ng/mlであった. CDDP3.5mg ip投与(6, 13日)群, TS-1単独群, 対照群ではMST36, 28, 32日で差を認めなかった. しかし, CDDP+TS-1(8mg/kg)群ではMST50日で有意に他の3群より生存率が良好であった. DOC8mg/kg, 2mg/kg ip投与群ではMST90, 63日で, それぞれ4匹, 1匹は腹膜播種が消失していた. DOC8mg/kg ip投与後は8時間後も腹水中DOC濃度(4.58±0.28μg/ml)は高い濃度を維持していたが, iv投与では腹水中濃度はip投与後に比べ1/100の値であった. また, 腹膜播種組織内のDoc濃度はip投与8時間ではiv投与後に比べ有意に高い値(4.65±1.33μg/gr)を示した. CBDCA50mg/kg(day3, 7ip)100mg/kg(day3, ip)投与群では有意に対照群より生存率が良好であった. MSTは対照群26.3日, 100mg/kg群37.7日, 50mg/kg群40.3日であった. しかし, 体重減少を認めた例はなかった. 以上より胃癌高度腹膜転移株MKN-45-Pによる腹膜播種モデルにおいて, 5-Fu ip, Ts-1 po+CDDP ip, Doc ip, CBDCA ip療法は有効であり, 臨床への応用が期待される. |
PH-PR-SHIMADA-T-1635.pdf (3.5 MB)
.png)
