Pulmonary artery perfusion of doxorubicin with blood flow occlusion: pharmacokinetics and treatment in a metastatic sarcoma model.

BACKGROUND

We compared pharmacokinetics, toxicity, and treatment efficacy of pulmonary artery perfusion of low-dose doxorubicin with blood flow occlusion to intravenous doxorubicin injection in a metastatic sarcoma model in the rat.

METHODS

Animals received left pulmonary artery perfusion with 0.1, 0.2, or 0.5 mg/kg doxorubicin at a rate of 0.1 mL/min for 1 minute with 20 minutes of blood flow occlusion. Doxorubicin levels of the lung, heart, and serum were assayed. Body weights after treatment were recorded and right pneumonectomy was performed. The results were compared with those in rats that received 5 mg/kg doxorubicin by intravenous injection or the saline group. Pulmonary sarcoma metastases were treated with 0.5 mg/kg doxorubicin through lung perfusion or intravenously, or with saline solution.

RESULTS

Doxorubicin levels in the lung, heart, and serum were 112.1 +/- 9.2 micrograms/g, 1.7 +/- 0.2 microgram/g, and 0.3 +/- 0.1 microgram/mL in the group with 0.5 mg/kg doxorubicin perfusion, versus 24.8 +/- 1.9 microgram/g, 10.1 +/- 1.3 microgram/g, and 0.7 +/- 0.2 microgram/mL in the intravenous group (p < 0.05). Animals had normal growth patterns and survived after right pneumonectomy in the perfused group, whereas the intravenous group failed to thrive. No tumors were found or a significant reduction in nodules was noted in the lungs treated with perfusion as compared with untreated right lungs or the intravenous and saline groups.

CONCLUSION

This chemotherapy model has important pharmacokinetic advantages and causes an increased treatment response for pulmonary metastatic sarcoma with minimal systemic and local toxicity as compared with systemic doxorubicin administration.