吉西他滨隔离肺灌注在大鼠肺转移模型中的毒性和疗效

Toxicity and efficacy of isolated lung perfusion with gemcitabine in a rat model of pulmonary metastases.

作者信息

Van Putte B P, Hendriks J M H, Romijn S, De Greef K, Van Schil P E Y

机构信息

Department of Cardiothoracic Surgery, St. Antonius Hospital, Nieuwegein, The Netherlands.

出版信息

Thorac Cardiovasc Surg. 2006 Mar;54(2):129-33. doi: 10.1055/s-2005-872868.

DOI:10.1055/s-2005-872868

PMID:16541356

Abstract

BACKGROUND

Long-term toxicity and efficacy of isolated left lung perfusion (ILuP) with gemcitabine (GCB) were studied in a rat model of metastatic pulmonary adenocarcinoma.

TOXICITY

Forty rats were randomized into six groups and administered 160 or 320 mg/kg GCB or buffered starch, received either via intravenous injection (i.v.) or via ILuP. Efficacy experiment: Rats with unilateral metastases had ILuP with 320 mg/kg GCB (maximally tolerated dose administered by ILuP), while rats with bilateral metastases had an i.v. injection of 160 mg/kg GCB (maximally tolerated dose given by i.v.).

RESULTS

TOXICITY experiment: After i.v. treatments, all rats receiving 320 mg/kg GCB died within one week, while rats who had received 160 mg/kg GCB had a survival rate of 60%. After ILuP with 160 mg/kg GCB and 320 mg/kg GCB, survival rates were 83% in both groups. A significant increase in collagen deposits was observed for ILuP with 320 mg/kg GCB compared to rats treated i.v. with 160 mg/kg GCB. Efficacy experiment: Median survival of ILuP rats treated with 320 mg/kg (38 +/- 4 days) was significantly longer compared to i.v. rats treated with 160 mg/kg (27 +/- 2 days; p = 0.02).

CONCLUSIONS

ILuP with GCB prolongs survival in experimental metastatic adenocarcinoma while no major acute or long term toxicity is observed.

摘要

背景

在转移性肺腺癌大鼠模型中研究了吉西他滨（GCB）隔离左肺灌注（ILuP）的长期毒性和疗效。

毒性

40只大鼠随机分为6组，分别给予160或320mg/kg吉西他滨或缓冲淀粉，通过静脉注射（i.v.）或ILuP给药。疗效实验：单侧转移的大鼠接受320mg/kg吉西他滨的ILuP（ILuP给药的最大耐受剂量），而双侧转移的大鼠静脉注射160mg/kg吉西他滨（静脉注射给药的最大耐受剂量）。

结果

毒性实验：静脉治疗后，所有接受320mg/kg吉西他滨的大鼠在一周内死亡，而接受160mg/kg吉西他滨的大鼠存活率为60%。在160mg/kg和320mg/kg吉西他滨的ILuP后，两组的存活率均为83%。与静脉注射160mg/kg吉西他滨治疗的大鼠相比，320mg/kg吉西他滨的ILuP组观察到胶原沉积显著增加。疗效实验：接受320mg/kg治疗的ILuP大鼠的中位生存期（38±4天）明显长于接受160mg/kg治疗的静脉注射大鼠（27±2天；p=0.02）。