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

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 (MTD) 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 MTD of melphalan was determined at 45 mg when given at 37°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.