Background : Current 5-year survival after complete resection of pulmonary metastases is 20-40%, and many patients develop intrathoracic recurrences. Isolated lung perfusion (ILuP) is an experimental technique to deliver high-dose chemotherapy to the lung without systemic exposure. A phase I trial of ILuP with melphalan (MN) combined with pulmonary metastasectomy for resectable lung metastases was conducted in order to define the dose limiting toxicity (DLT) and maximum tolerated dose (MTD).
Methods : From May 2001 to August 2003, 16 patients underwent ILuP with MN, followed by surgical resection of lung metastases. Patients were treated with increasing MN doses (levels 15, 30, 45, 60 mg). For each dose level, normothermia (37°C) and hyperthermia (42°C) were evaluated (n=3 per level). Serum samples were obtained during the procedure. Pulmonary, hematologic and non-hematologic toxicities were recorded. The primary tumor was colorectal in 7 patients, renal in 5, sarcoma in 3, and salivary gland in 1. ILuP was performed unilaterally in 11 patients, and staged bilaterally in 5.
Results : In total, 21 procedures of ILuP with complete metastasectomy were performed without technical difficulties. Operative mortality was 0%, and no systemic toxicity was encountered. Grade 3 pulmonary toxicity developed at a dose of 60 mg of MN at 37°C in 2 out of 3 patients in this level, terminating the trial.
Conclusions : ILuP with melphalan combined with pulmonary metastasectomy is feasible. DLT occurred at a dose of 60 mg MN at 37°C and MTD was set at 45 mg MN at 42°C.