Isolated Lung Perfusion with Adriamycin

Isolated in vivo single-lung perfusion with an Adriamycin-containing whole-blood perfusate was performed in three groups of dogs after establishing adequate controls. The procedure, performed through a left thoracotomy, was followed two weeks later by a contralateral pneumonectomy. Survival following pneumonectomy was used as the ultimate end point in assessing perfusion toxicity. Groups I and I1 had high mortality rates but provided valuable information concerning perfusion methods, venous drainage techniques, drug dosage schedules, and perfusate flow rates. The group 111 study consisted of five dogs perfused for 45 minutes at flow rates suficient to maintain mean pulmonary artery pressure at 12-15 mm Hg. An initial Adriamycin (Adr) dosage of 0.5 rg/ml in the plasma perfusate resulted in mean peak Adr lung tissue levels of 3.8 k 1.06 pg/g. All animals survived right pneumonectomy 19 f 4 days later. Three dogs have been killed and histologic examination showed only mild focal pleural and subpleural interstitial fibrosis. Based on these studies it is concluded that isolated singlelung perfusion is a reproducibly safe technique and that a dosage of Adr has been identified which produces no apparent toxity in a large animal model. A clinical trial is currently in progress. Cancer 52:404-409, 1983. HEN PRIMARY BONE and Soft tissue SarCOmaS W metastasize, the initial site of metastatic spread is usually to the lungs.'.' Resection of these nodules when possible now yields five-year survival rates of 2530%.3-6 A significant proportion of patients, however, are unresectable and chemotherapy becomes the only treatment option. Adriamycin is considered the most active drug against sarcoma. Remissions have been achieved in 33-40% of patient^.'.^ Currently, no other single-agent has as much activity against all sarcoma cell types.' Although a doseresponse relationship probably exists with Adriamycin (doxorubicin)," the threat of cardiotoxicity often limits the effectiveness of the drug. This study describes a technique for in vivo isolated lung perfusion with an Adriamycin-containing perfusate capable of delivering a high