Li T S, Sugi K, Ueda K, Nawata K, Nawata S, Esato K
First Department of Surgery, Yamaguchi University School of Medicine, Japan.
Anticancer Res. 1998 Nov-Dec;18(6A):4171-6.
The present study was conducted to evaluate the toxicity, pharmacokinetics and anti-tumor potency of isolated lung perfusion (ILP) with cisplatin in a visible lung tumor nodule model in rats.
A solitary tumor nodule was established by the injection of Methylcholanthrene-induced sarcoma cells into the left lung. Thirty rats were randomized to undergo ILP with either 0.1, 0.25, or 0.5 mg/mL cisplatin and buffered hespan (BHE), or with an intravenous injection of 1.0 or 2.5 mg cisplatin.
The highest dose of cisplatin tolerated by the rats was 0.1 mg/mL for perfusion. A much higher platinum concentration in the tumor, of 6.67 +/- 1.64 vs. 2.51 +/- 0.60 micrograms/g tissue, but a significantly lower concentration in the serum and kidneys, was achieved by perfusion compared to that achieved by intravenous injection. A significantly lower tumor weight and 20% complete treatment response was achieved in rats given cisplatin than in those given BHE perfusion at 43.9 +/- 11.6 vs. 226.3 +/- 44.6 mg.
ILP with cisplatin achieved superior results to intravenous injection according to the levels of toxicity and pharmacokinetic analysis, and it was effective against a visible tumor nodule model in rats.
本研究旨在评估顺铂隔离肺灌注（ILP）在大鼠可见肺肿瘤结节模型中的毒性、药代动力学和抗肿瘤效力。
通过将甲基胆蒽诱导的肉瘤细胞注射到左肺建立孤立肿瘤结节。30只大鼠被随机分为接受0.1、0.25或0.5mg/mL顺铂与缓冲羟乙基淀粉（BHE）的ILP，或静脉注射1.0或2.5mg顺铂。
大鼠耐受的顺铂最高灌注剂量为0.1mg/mL。与静脉注射相比，灌注在肿瘤中实现了更高的铂浓度，分别为6.67±1.64与2.51±0.60μg/g组织，但在血清和肾脏中的浓度显著更低。给予顺铂的大鼠肿瘤重量显著更低，完全治疗反应率为20%，而给予BHE灌注的大鼠为43.9±11.6与226.3±44.6mg。
根据毒性和药代动力学分析水平，顺铂ILP取得了优于静脉注射的结果，并且对大鼠可见肿瘤结节模型有效。
