Oshima Takashi, Yamada Roppei, Hatori Shinsuke, Kunisaki Chikara, Imada Toshio
Gastroenterological Center, Yokohama City University Medical Center, Yokohama 232-0024, Japan.
Oncol Rep. 2006 Aug;16(2):361-6.
The response of gastric cancer with peritoneal dissemination to systemic chemotherapy may be negatively affected by poor drug delivery due to the blood-peritoneal barrier. However, S-1 has been reported to be effective. We examined the pharmacokinetics of S-1 in 14 patients who had gastric cancer with peritoneal dissemination. S-1 was given from the morning of the day before surgery to the morning of surgery. Concentrations of 5-fluorouracil (5-FU) and gimeracil (CDHP) were measured in the serum, ascites, disseminated peritoneal nodes, and normal peritoneum. There was a strong correlation between 5-FU and CDHP concentrations in peritoneal tissues. The concentrations of 5-FU and CDHP in the serum were similar to those in ascites. The concentration of 5-FU was significantly higher in disseminated nodes than in the normal peritoneum. After administration of S-1 to gastric cancer patients with peritoneal dissemination, 5-FU and CDHP in the serum linearly pass through the peritoneum and enter the ascites. High concentrations of 5-FU selectively penetrate disseminated peritoneal cells.
由于血-腹膜屏障导致药物递送不佳,胃癌伴腹膜播散对全身化疗的反应可能受到负面影响。然而,据报道S-1是有效的。我们研究了14例胃癌伴腹膜播散患者中S-1的药代动力学。S-1于手术前一天上午至手术当天上午给药。在血清、腹水、播散的腹膜结节和正常腹膜中测量5-氟尿嘧啶(5-FU)和吉美嘧啶(CDHP)的浓度。腹膜组织中5-FU和CDHP浓度之间存在强相关性。血清中5-FU和CDHP的浓度与腹水中的浓度相似。5-FU在播散结节中的浓度显著高于正常腹膜。对胃癌伴腹膜播散患者给予S-1后,血清中的5-FU和CDHP线性穿过腹膜并进入腹水。高浓度的5-FU选择性地穿透播散的腹膜细胞。