Mohamed F, Marchettini P, Stuart O A, Yoo D, Sugarbaker P H
The Washington Cancer Institute, Washington Hospital Center, 110 Irving Street, NW, Washington, DC 20010, USA.
Eur J Surg Oncol. 2003 Apr;29(3):261-5. doi: 10.1053/ejso.2002.1397.
Intraperitoneal chemotherapy administration results in high drug concentration locally with low systemic toxicity. We compared the pharmacokinetics of paclitaxel infused intraperitoneally in two isotonic carrier solutions, 1.5% dextrose peritoneal dialysis solution (peritoneal dialysis solution) and hetastarch (6% hydroxyethyl starch), a high molecular weight solution.
Twenty patients with peritoneal carcinomatosis were randomized into one of two groups to receive early postoperative intraperitoneal chemotherapy with paclitaxel for 5 consecutive days following cytoreductive surgery. One group (8 patients) received paclitaxel in one litre of peritoneal dialysis solution; the other group (12 patients) received paclitaxel in one litre of hetastarch. Samples of peritoneal fluid and venous blood were taken during the 23 h dwell time. Volumes of chemotherapy solution were recorded and concentrations of paclitaxel determined by high performance liquid chromatography.
Hetastarch clearance from the peritoneal cavity was reduced when compared to peritoneal dialysis solution. The mean volume of fluid remaining in the peritoneal cavity at 23 h was 900 ml +/-373.7 (SD) with hetastarch, and 285 ml (+/-157.5) with peritoneal dialysis solution (P=0.0022). The mean total amount of paclitaxel in the peritoneal cavity at 23 h was 2.597 mg (+/-1.57) with hetastarch and 0.772 mg (+/-0.667) with peritoneal dialysis solution (P=0.0152).
These data show that hetastarch increased the exposure of peritoneal surfaces to paclitaxel by increasing the volume of solution with no decrease in drug concentration. Residual tumour cells within the peritoneal cavity may show an increased response to paclitaxel with hetastarch as a carrier solution.
腹腔内化疗给药可使局部药物浓度升高，全身毒性降低。我们比较了在两种等渗载体溶液（1.5%葡萄糖腹膜透析液（腹膜透析液）和羟乙基淀粉（6%羟乙基淀粉），一种高分子量溶液）中腹腔内输注紫杉醇的药代动力学。
20例腹膜癌患者随机分为两组，在肿瘤细胞减灭术后连续5天接受术后早期腹腔内紫杉醇化疗。一组（8例患者）在1升腹膜透析液中接受紫杉醇；另一组（12例患者）在1升羟乙基淀粉中接受紫杉醇。在23小时的留置时间内采集腹腔液和静脉血样本。记录化疗溶液的体积，并通过高效液相色谱法测定紫杉醇的浓度。
与腹膜透析液相比，羟乙基淀粉从腹腔的清除率降低。23小时时腹腔内残留液体的平均体积，羟乙基淀粉组为900毫升±373.7（标准差），腹膜透析液组为285毫升（±157.5）（P = 0.0022）。23小时时腹腔内紫杉醇的平均总量，羟乙基淀粉组为2.597毫克（±1.57），腹膜透析液组为0.772毫克（±0.667）（P = 0.0152）。
这些数据表明，羟乙基淀粉通过增加溶液体积而不降低药物浓度，增加了腹腔表面对紫杉醇的暴露。以羟乙基淀粉作为载体溶液时，腹腔内残留的肿瘤细胞对紫杉醇的反应可能会增强。
