Isolated lung perfusion for patients with unresectable metastases from sarcoma: A Phase I trial

Background. In patients with unresectable pulmonary metastases from sarcoma , systemic chemotherapy has had limited efficacy possibly because of dose-l imiting toxicities. Isolated lung perfusion is an alternative method of del ivering high-dose chemotherapy to the lungs while minimizing systemic toxic ities. We present the results of our Phase I trial of isolated lung perfusi on with doxorubicin hydrochloride in such a group of patients. Methods. From May 1995 to June 1997, 8 patients with unresectable metastase s from sarcoma limited to the lungs underwent isolated lung perfusion with doxorubicin. A dose-escalation schedule starting at 40 mg/m(2) was used. Se ven patients were treated with a dose of 40 mg/m(2) or less, and 1 patient received 80 mg/m(2). Blood, tumor, acid normal lung samples were obtained a t various time points during the operation. Patients were evaluated for car diac, pulmonary, and other toxicities. Results. The doxorubicin concentrations in both normal lung and tumor corre lated directly with the amount of doxorubicin in the perfusate. The tumors took up less doxorubicin than the lung. All patients had minimal or undetec table systemic levels of doxorubicin at the conclusion of the perfusion. Th ere were no cardiac or other systemic toxicities. In the 7 patients perfuse d with 40 mg/m(2) or less of doxorubicin, there was a significant decrease in the forced expiratory volume in 1 second and a trend toward a significan t decrease in diffusing capacity. The patient who received 80 mg/m(2) under went lung scanning postoperatively, and scans showed no ventilation or perf usion in the perfused lung. There were no perioperative deaths. Two patient s are alive with disease, and 6 patients died of disease. The median follow -up is 11 months and the longest, 31 months. There were no partial or compl ete responses. One patient had stabilization of disease in the perfused lun g, whereas the lesions in the untreated lung progressed markedly. Conclusion. Isolated lung perfusion is well tolerated by patients and effec tively delivers high doses of doxorubicin to the lung and tumor tissues whi le minimizing systemic toxicities. A single dose of 80 mg/m(2) resulted in substantial injury to the lung. There were no partial or complete responses in patients perfused with doxorubicin at the maximum tolerated dose of 40 mg/m(2). Isolated lung perfusion remains a model for testing new and innova tive therapies for metastatic sarcoma. (C) 2000 by The Society of Thoracic Surgeons.