REGIONAL CHEMOTHERAPY VIA PULMONARY-ARTERY WITH FLOOD FLOW OCCLUSION IN A SOLITARY TUMOR NODULE MODEL

This study is to evaluate low dose doxorubicin pulmonary artery perfus ion with blood flow occlusion compared to systemic administration in a model of solitary intrapulmonary sarcoma nodule in the rat. Tumor nod ule was developed via injection of methylcholanthrene-induced sarcoma into the left lung. Doxorubicin was perfused into the left pulmonary a rtery at a rate of 50 mu l/min for 2 min with 20 min blood flow blocka ge in all experiments. Pharmacokinetics, toxicity, treatment efficacy were compared between lung perfusion groups and intravenous groups. Do xorubicin levels in tumor, left lung, right lung, heart and serum were measured. Animal daily weights were recorded and a right pneumonectom y was performed following treatment to assess toxicity and tolerated p erfusion dose. Tumors were weighed following treatment to evaluate tre atment efficacy. Doxorubicin delivered via pulmonary artery caused a s ignificant higher drug level in tumor tissue and perfused lung with a low drug level in heart, right lung and serum as compared to intraveno us administration. Animals in perfusion groups and normal growth patte rn and survived after pneumonectomy when a dose of 0.5mg/kg doxorubici n was perfused. Tumor weight was significantly decreased after treated with 0.5mg/kg of doxorubicin lung perfusion as compared to same dose of doxorubicin intravenous treatment. Pulmonary artery perfusion with blood flow occlusion may offer an effective lung chemotherapeutic mode l. 0.5mg/kg doxorubicin for lung perfusion has acceptable local lung t oxicity and no significant systemic toxicity and is pharmacokineticall y and therapeutically superior to systemic administration in this soli tary intrapulmonary tumor nodule model in the rat.