ISOLATED SINGLE-LUNG PERFUSION WITH DOXORUBICIN IS EFFECTIVE IN ERADICATING SOFT-TISSUE SARCOMA LUNG METASTASES IN A RAT MODEL

The only effective therapy for patients with metastatic soft tissue sa rcoma in the lung is surgical resection, with a 5-year survival of app roximately 25 %. Because systemic chemotherapy has not significantly a ffected survival in these patients, we began to investigate locoregion al chemotherapy. We have previously shown that isolated single lung pe rfusion with doxorubicin in the rat results in higher lung tissue leve ls and lower systemic toxicity than does high-dose intravenous therapy , In the present study, we examined the safety of isolated lung perfus ion,vith doxorubicin and its efficacy in the treatment of experimental pulmonary metastases from soft tissue sarcoma. In experiment 1, 15 F3 44 rats were randomized into three groups (n = 5): group I had isolate d left lung perfusion with doxorubicin 320 mu g/ml in saline solution; group II had left isolated lung perfusion with doxorubicin 480 mu g/m l and group III with doxorubicin 640 mu g/ml. Ah perfusions with doxor ubicin were at 0.5 ml/min for 10 minutes followed by perfusion of sali ne solution for 5 minutes. On day 21, all animals underwent right (con tralateral) pneumonectomy and were observed for over 10 days. In exper iment 2, two groups of F344 rats were injected intravenously with 10(7 ) viable methylcholanthrene-induced sarcoma cells on day 0. On day 7, group I (n = 12) had left isolated lung perfusion with saline solution only and group II (n = 15) had isolated lung perfusion with doxorubic in 320 mu g/ml. On day 21, all animals were killed, and their lungs we re stained for metastases. Routine histologic sections from three anim als from group II were examined. In experiment 1, 80% of the animals i n group I survived contralateral pneumonectomy. There were no survivor s in groups II and III. In experiment 2, three animals died after isol ated lung perfusion (one from group I and two from group II), and one animal (group I) was excluded because of mediastinal tumor. All animal s in both groups had massive tumor replacement of the right (untreated ) lung. Group I animals had massive tumor replacement of the left (tre ated) lung, whereas animals in group II had eradication of metastases in nine of ten cases; no microscopic evidence of tumor was detected in all three animals evaluated for microscopic disease. Isolated lung pe rfusion with doxorubicin 320 mu g/ml is safe and effective in eradicat ing experimental pulmonary sarcoma metastases in this model.