进展期胃癌术前卡铂腹腔、静脉化疗肿瘤组织聚积浓度的比较及药代动力学研究

Preoperative intraperitoneal versus intravenous carboplatin chemotherapy for advanced gastric cancer, pharmacokinetics and drug accumulation study

目的探讨不同给药途径抗癌药在肿瘤组织内药物浓度的聚积性。方法对２０例可切除进展期胃癌比较研究了术前卡铂腹腔、静脉化疗药代动力学。术前卡铂３００ｍｇ／ｍ２加生理盐水７５０ｍｌ分别腹腔（ｉｐ）、静脉（ｉｖ）给药，注射后１６０～１８０分钟取腹腔液、门静脉及外周血，２４０～２７０分钟取癌组织、癌旁正常组织、大网膜、腹膜及转移阴性淋巴结，应用高效液相色谱法（ＨＰＬＣ）测定总铂浓度。结果腹腔给药各组织内聚积较高的药物浓度，其中腹膜浓度最高，超出静脉给药组近４倍，癌组织内含量高于正常组织。腹腔液、门静脉、外周血超出静脉给药组１３，３，１．５倍。结论术前腹腔化疗不仅提高了腹膜、肿瘤组织内浓度，延长药物作用时间，而且大大降低癌细胞生物活性，使对药物敏感的细胞得到控制，对消灭亚临床灶，改善临床病期，提高手术切除率，控制医源性转移颇为重要。

Objective To examine the accumulation of anticancer drugs in tumor tissues by different routes of administration. Methods Pharmacokinetic comparison of preoperative intraperitoneal (ip) and intravenous (iv) carboplatin chemotherapy was done in 10 patients each with advanced, resectable gastric cancer. Preoperatively, 300 mg/m 2 carboplatin in 750 ml 0.9% sodium chloride was administered by ip or iv. At 160 180 minutes after drug administration, peritoneal fluid, portal vein blood and peripheral blood were taken. At 240～270 minutes later, cancer tissues, peritumor normal tissues, omentum majus, peritoneum and cancer free lymphnodes were collected during operation. Total carboplatin concentrations were measured by high performance liquid chromatography (HPLC).Results High concentrations of carboplatin were found in all tissues by ip administration. Drug concentration was highest in the peritonaeum, being 4 times as high as that after iv administration. Cancer tissue had higher drug concentration than did peritumor normal tissues. Compared to those after iv administration, concentrations in the peritoneal fluid, portal vein blood and peripheral blood were 13, 3 and 1.5 times as high, respectively. No significant differences were observed in drug concentrations in the peritoneum, omentum majus and lymph nodes after iv administration.Conclusion For gastric cancer, carboplatin chemotherapy by ip administration is a better route for clinical practice.