TY - JOUR
T1 - Isolated lung perfusion with melphalan for resectable lung metastases: A phase I clinical trial
AU - Hendriks, Jeroen M. H.
AU - Grootenboers, Marco J. J. H.
AU - Schramel, Franz M. N. H.
AU - van Boven, Wim J.
AU - Stockman, Bernard
AU - Seldenrijk, Cornelis A.
AU - ten Broecke, Pieter
AU - Knibbe, Catherijne A. J.
AU - Slee, Peter
AU - de Bruijn, Ernst
AU - Vlaeminck, Renate
AU - Heeren, Jos
AU - Vermorken, Jan B.
AU - van Putte, Bart
AU - Romijn, Sander
AU - van Marck, Eric
AU - van Schil, Paul E. Y.
PY - 2004
Y1 - 2004
N2 - Background. Current 5-year survival after complete resection of pulmonary metastases is 20% to 40%, and many patients develop intrathoracic recurrences. Isolated lung perfusion is an experimental technique to deliver high-dose chemotherapy to the lung without systemic exposure. A phase I trial of isolated lung perfusion with melphalan (MN) combined with pulmonary metastasectomy for resectable lung metastases was conducted to define the dose-limiting toxicity and maximum tolerated dose. Methods. From May 2001 to August 2003, 16 patients underwent isolated lung perfusion with MN, followed by surgical resection of lung metastases. Patients were treated with increasing MN doses (15, 30, 45, and 60 mg). For each dose level, normothermia (37degreesC) and hyperthermia (42degreesC) were evaluated (n = 3 per level). Serum samples were obtained during the procedure. Pulmonary, hematologic, and nonhematologic toxicities were recorded. The primary tumor was colorectal in 7 patients, renal in 5, sarcoma in 3, and salivary gland in 1. Isolated lung perfusion was performed unilaterally in 11 patients, and staged bilaterally in 5. Results. In total, 21 procedures of isolated lung perfusion 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 37degreesC in 2 of 3 patients at this dose, terminating the trial. Conclusions. Isolated lung perfusion with MN combined with pulmonary metastasectomy is feasible. Dose-limiting toxicity occurred at a dose of 60 mg of MN at 37degreesC, and the maximum tolerated dose was set at 45 mg of MN at 42degreesC. (C) 2004 by The Society of Thoracic Surgeons
AB - Background. Current 5-year survival after complete resection of pulmonary metastases is 20% to 40%, and many patients develop intrathoracic recurrences. Isolated lung perfusion is an experimental technique to deliver high-dose chemotherapy to the lung without systemic exposure. A phase I trial of isolated lung perfusion with melphalan (MN) combined with pulmonary metastasectomy for resectable lung metastases was conducted to define the dose-limiting toxicity and maximum tolerated dose. Methods. From May 2001 to August 2003, 16 patients underwent isolated lung perfusion with MN, followed by surgical resection of lung metastases. Patients were treated with increasing MN doses (15, 30, 45, and 60 mg). For each dose level, normothermia (37degreesC) and hyperthermia (42degreesC) were evaluated (n = 3 per level). Serum samples were obtained during the procedure. Pulmonary, hematologic, and nonhematologic toxicities were recorded. The primary tumor was colorectal in 7 patients, renal in 5, sarcoma in 3, and salivary gland in 1. Isolated lung perfusion was performed unilaterally in 11 patients, and staged bilaterally in 5. Results. In total, 21 procedures of isolated lung perfusion 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 37degreesC in 2 of 3 patients at this dose, terminating the trial. Conclusions. Isolated lung perfusion with MN combined with pulmonary metastasectomy is feasible. Dose-limiting toxicity occurred at a dose of 60 mg of MN at 37degreesC, and the maximum tolerated dose was set at 45 mg of MN at 42degreesC. (C) 2004 by The Society of Thoracic Surgeons
U2 - https://doi.org/10.1016/j.athoracsur.2004.05.058
DO - https://doi.org/10.1016/j.athoracsur.2004.05.058
M3 - Article
C2 - 15561001
SN - 0003-4975
VL - 78
SP - 1919
EP - 1926
JO - Annals of Thoracic Surgery
JF - Annals of Thoracic Surgery
IS - 6
ER -