Murata Satoshi, Yamamoto Hiroshi, Shimizu Tomoharu, Naitoh Hiroyuki, Yamaguchi Tsuyoshi, Kaida Sachiko, Takebayashi Katsushi, Miyake Toru, Tani Tohru, Tani Masaji
Department of Surgery, Shiga University of Medical Science, Otsu, Shiga, Japan.
Cancer Center, Shiga University of Medical Science Hospital, Otsu, Shiga, Japan.
J Surg Oncol. 2018 Mar;117(4):671-677. doi: 10.1002/jso.24906. Epub 2017 Dec 19.
Optimized drug regimens for hyperthermic intraperitoneal chemotherapy (HIPEC) have not been standardized completely in patients with advanced gastric cancer (GC). We evaluated an optimized anti-tumor protocol comprising 5-fluorouracil (5-FU) combined with cisplatin (CDDP) and mitomycin C (MMC) in vitro for clinical use of HIPEC.
The sensitivities of 5-FU, CDDP, or MMC, alone or in combination, using different drug concentrations, exposure times, and hyperthermic conditions (42°C) were determined in vitro by the CD-DST method using 3 different differentiated GC cell lines.
The tumor cell growth-inhibitory effect of 5-FU was concentration-dependent for all cell lines. In addition, 5-FU showed a hyperthermic sensitization effect at all drug concentrations for all cell lines. The appropriate concentration of each drug was 5-FU, 200 µg/mL; CDDP, 10 µg/mL; MMC, 2 µg/mL. Under hyperthermic conditions, most growth-inhibitory effects for each drug at 30 min was equivalent to 60 min of exposure; use of three drugs combined significantly inhibited growth compared with any of the drugs alone.
An appropriate in vitro intraperitoneal chemotherapy regimen for GC was combined use of 5-FU, CDDP, and MMC at 42°C for 30 min.
晚期胃癌（GC）患者的热灌注化疗（HIPEC）优化药物方案尚未完全标准化。我们在体外评估了一种由5-氟尿嘧啶（5-FU）联合顺铂（CDDP）和丝裂霉素C（MMC）组成的优化抗肿瘤方案，用于HIPEC的临床应用。
使用3种不同分化的GC细胞系，通过CD-DST方法在体外测定5-FU、CDDP或MMC单独或联合使用不同药物浓度、暴露时间和热疗条件（42°C）时的敏感性。
5-FU对所有细胞系的肿瘤细胞生长抑制作用呈浓度依赖性。此外，5-FU在所有药物浓度下对所有细胞系均显示出热敏化作用。每种药物的合适浓度为5-FU，200μg/mL；CDDP，10μg/mL；MMC，2μg/mL。在热疗条件下，每种药物在30分钟时的大多数生长抑制作用相当于暴露60分钟；与任何一种药物单独使用相比，三种药物联合使用显著抑制生长。
GC合适的体外腹腔化疗方案是在42°C下联合使用5-FU、CDDP和MMC 30分钟。
