Objective : Toxicity and long-term survival after isolated lung perfusion (ILuP) with gemcitabine (GCB) were studied in a rat model of metastatic pulmonary adenocarcinoma.
Methods : Toxicity: Seventy-two rats were randomized between intravenous injection (IV) and ILuP on day 0. Doses of 40 mg/kg (n=6), 80 mg/kg (n=6), 160 mg/kg (n=6), 320 mg/kg (n=6) and buffered hespan (controls; n=6) were given in the ILuP arm. Doses of 40 mg/kg (n=10), 80 mg/kg (n=10), 160 mg/kg (n=10), 320 mg/kg (n=6) and buffered hespan (controls; n=6) were given in the IV arm. At day 21, rats underwent a right pneumonectomy and survival was recorded. At day 90, lungs were harvested for histologic analysis. Efficacy: On day 0, 20 rats were randomized into four groups: group 1 (n=4) received tumour cells IV for induction of bilateral lung metastases, whereas group 2 received IV treatment with GCB 160 mg/kg at day 7 (n=6). Groups 3 (n=4) and 4 (n=6) underwent a 10-min occlusion of the right pulmonary artery during tumour cell injection for induction of unilateral left lung metastases. On day 7, group 3 received no treatment while group 4 underwent ILuP with GCB 320 mg/kg.
Results : Toxicity: After IV treatment, all rats receiving 320 mg/kg died within one week while GCB 160 mg/kg had a survival rate of 60%. After ILuP with GCB 160 mg/kg and 320 mg/kg survival rates were 83% in both groups. A mild increase in collagen deposits was seen for ILuP 320 mg/kg after 3 months compared to controls. Efficacy: Median survival of group 4 (38±4 days) was significantly longer compared to group 1 (MST: 28days), group 2 (MST:27days) and group 3 (MST:28days).
Conclusion : ILuP with GCB prolongs survival in an experimental model of pulmonary metastatic adenocarcinoma while no major acute or chronic (after 3 months) toxicity is observed.