Long-term survival of a phase I clinical trial of isolated lung perfusion with melphalan for resectable lung metastases

Willem A. den Hengst, Bart P. van Putte, Jeroen M. H. Hendriks, Bernard Stockman, Wim-Jan P. van Boven, Joost Weyler, Franz M. N. H. Schramel, Paul E. Y. van Schil

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Abstract

Objective Surgical resection of lung metastases is a widely accepted procedure but 5 year survival rates remain low and vary between 20% and 50% Isolated lung perfusion (ILuP) is an experimental technique to deliver a high dose of chemotherapy to the lung without systemic toxicity Long term survival of ILuP has not been reported yet and was determined in a phase I clinical trial Methods From May 2001 to December 2004 a phase I clinical trial was conducted to define the maximum tolerated dose (MID) of ILuP with melphalan Twenty nine procedures were performed in 23 patients The primary tumour was colorectal in 10 patients, renal in eight sarcoma in four and salivary gland in one Toxicity results were previously reported and the MID of melphalan was determined at 45 mg when given at 37 degrees C Follow up was updated and long term survival is reported Results Follow up was complete, except for one patient who was lost to follow up after 8 months After a median follow up of 62 months, 6 out of 23 patients were alive and free of recurrent disease One patient died after a subsequent operation Sixteen patients developed recurrent disease, of whom 11 died Nine patients had intrathoracic recurrent disease only, one intra and extrathoracic recurrences each and five extrathoracic only In one patient, the location of recurrence was not known Overall and disease free 5 year survival rates were 54 8 +/- 10 6% and 27 5 +/- 9 5%, respectively with an overall median survival time (MST) of 84 months (95% confidence interval (CI) 41-128) and disease free MST of 19 months (95% CI 4-34) Lung function and diffusion capacity initially dropped 1 month after perfusion slightly improving afterwards Radiographic follow up with chest computed tomography showed no long term toxicity from ILuP Conclusion ILuP can be applied without major long term pulmonary toxicity Five year survival rate, overall and disease free MST in this phase I clinical trial are promising This is another incentive to perform further studies with ILuP (C) 2010 European Association for Cardio Thoracic Surgery Published by Elsevier B V All rights reserved
Original languageEnglish
Pages (from-to)621-627
JournalEuropean Journal of Cardio-thoracic Surgery
Volume38
Issue number5
DOIs
Publication statusPublished - 2010
Externally publishedYes

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