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

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. Materials: Toxicity: Forty rats were randomized into six groups and administered 160 or 320 mg/kg GCB or buffered starch, received either via intravenous injection (IV) 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 IV injection of 160 mg/kg GCB (maximally tolerated dose given by IV). Results: Toxicity experiment: After IV 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 IV 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 IV 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. © Georg Thieme Verlag KG.