Multicenter phase II clinical trial of isolated lung perfusion in patients with lung metastases

Abstract Background Up to 66% of patients show local pulmonary disease progression after pulmonary metastasectomy. Regional treatment with isolated lung perfusion (ILuP) may improve local control with minimal systemic side-effects. The aim of this study is to evaluate local and distant control after ILuP and to determine the effect on overall survival in comparison with historical controls. Secondary, it aims to confirm the safety and feasibility of ILuP. Methods 107 patients with resectable pulmonary metastases of colorectal carcinoma (CRC), osteosarcoma and soft-tissue sarcoma were included in a prospective phase II study of pulmonary metastasectomy combined with ILuP with 45 mg melphalan at 37°C. Local and distant control, overall survival, lung function and 90-day mortality and morbidity were monitored. Results We report 0% mortality, low morbidity and no long-term pulmonary toxicity. For CRC median time to local pulmonary progression, median time to progression and median survival time were 31, 14 and 78 months, respectively. Median time to local progression was not reached for sarcoma while median time to progression and median survival time where 13 and 39 months, respectively. Five-year disease-free rate and pulmonary progression-free rate were 26% and 44% for CRC and 29% and 63% for sarcoma, respectively. Conclusions ILuP with melphalan combined with metastasectomy is feasible and safe. Compared to historical controls, favorable results were obtained in this phase II study regarding local control. Further evaluation of locoregional lung perfusion techniques with other chemotherapeutic drugs is warranted.