Kerr D J, Young A M, Neoptolemos J P, Sherman M, Van-Geene P, Stanley A, Ferry D, Dobbie J W, Vincke B, Gilbert J, el Eini D, Dombros N, Fountzilas G
CRC Institute for Cancer Studies, University of Birmingham, UK.
Br J Cancer. 1996 Dec;74(12):2032-5. doi: 10.1038/bjc.1996.672.
A novel peritoneal carrier solution, Icodextrin 20 (7.5%), has allowed exploration of prolonged, intraperitoneal (i.p.) infusion of the cytotoxic drug 5-fluorouracil (5-FU). A phase I and pharmacokinetic study was performed to determine the toxicities and maximum tolerated dose of prolonged and continuous intraperitoneal 5-FU in patients with peritoneal carcinomatosis. Seventeen patients were entered into this study. Each patient had a Tenckhoff catheter placed into the peritoneal cavity under general anaesthetic. After initial flushing and gradual increase in exchange volumes with Icodextrin 20, 5-FU was administered daily from Monday to Friday, 50% as a bolus in the exchange bag and 50% in an elastomeric infusor device delivering continuous 5-FU to the peritoneal cavity at 2 ml h-1. Treatment was continued for 12 weeks or until intolerable toxicity developed. Abdominal pain and infective peritonitis proved to be the main dose-limiting toxicities. Initial problems with infective peritonitis were overcome by redesign of the delivery system, and it proved possible to deliver 300 mg m-2 5-FU daily (5 days per week) for 12 weeks. Pharmacokinetic studies showed i.p. steady-state 5-FU concentrations (mean 47 500 ng ml-1) that were > 1000-fold higher than systemic venous levels (mean 30 ng ml-1).
一种新型腹膜载体溶液艾考糊精20（7.5%），使得对细胞毒性药物5-氟尿嘧啶（5-FU）进行长时间腹腔内输注成为可能。开展了一项I期药代动力学研究，以确定腹膜转移癌患者长时间持续腹腔内输注5-FU的毒性和最大耐受剂量。17例患者纳入本研究。每位患者在全身麻醉下将Tenckhoff导管置入腹腔。在初始冲洗并逐步增加艾考糊精20的交换量后，5-FU于周一至周五每日给药，50%作为推注加入交换袋，50%通过弹性输液装置以2 ml/h的速度持续输注至腹腔。治疗持续12周或直至出现无法耐受的毒性。腹痛和感染性腹膜炎被证明是主要的剂量限制性毒性。通过重新设计给药系统克服了初始的感染性腹膜炎问题，结果证明有可能每周5天、每天给予300 mg/m²的5-FU，持续12周。药代动力学研究显示腹腔内5-FU稳态浓度（平均47500 ng/ml）比全身静脉血水平（平均30 ng/ml）高1000倍以上。
