PULMONARY-ARTERY PERFUSION OF DOXORUBICIN WITH BLOOD-FLOW OCCLUSION -PHARMACOKINETICS AND TREATMENT IN A METASTATIC SARCOMA MODEL

Background. We compared pharmacokinetics, toxicity, and treatment effi cacy of pulmonary artery perfusion of low-dose doxorubicin with blood flow occlusion to intravenous doxorubicin injection in a metastatic sa rcoma model in the rat. Methods. Animals received left pulmonary arter y perfusion with 0.1, 0.2, or 0.5 mg/kg doxorubicin at a rate of 0.1 m L/min for 1 minute with 20 minutes of blood flow occlusion. Doxorubici n levels of the lung, heart, and serum were assayed, Body weights afte r treatment were recorded and right pneumonectomy was performed. The r esults were compared with those in rats that received 5 mg/kg doxorubi cin by intravenous injection or the saline group. Pulmonary sarcoma me tastases were treated with 0.5 mg/kg doxorubicin through lung perfusio n or intravenously, or with saline solution. Results. Doxorubicin leve ls in the lung, heart, and serum were 112.1 +/- 9.2 mu g/g, 1.7 +/- 0. 2 mu g/g, and 0.3 +/- 0.1 mu g/mL in the group with 0.5 mg/kg doxorubi cin perfusion, versus 24.8 +/- 1.9 mu g/g, 10.1 +/- 1.3 mu g/g, and 0. 7 +/- 0.2 mu g/mL in the intravenous group (p < 0.05). Animals had nor mal growth patterns and survived after right pneumonectomy in the perf used group, whereas the intravenous group failed to thrive. No tumors were found or a significant reduction in nodules was noted in the lung s treated with perfusion as compared with untreated right lungs or the intravenous and saline groups. Conclusion. This chemotherapy model ha s important pharmacokinetic advantages and causes an increased treatme nt response for pulmonary metastatic sarcoma with minimal systemic and local toxicity as compared with systemic doxorubicin administration.