PURPOSE: Isolated lung perfusion (ILuP) is a promising surgical technique to deliver high-dose chemotherapy with minimal systemic toxicity. An extension trial of a previous reported phase-I clinical trial of ILuP with melphalan combined with pulmonary metastasectomy for resectable lung metastases was conducted for evaluation of pulmonary function assessments.
METHODS: From May 2001 to December 2004, 16 patients in a phase-I trial were treated with ILuP according to a dose-escalation schedule with 15, 30, 45 and 60 mg melphalan for 30 minutes until dose limiting toxicity was met followed by surgical resection of pulmonary metastases. Normothermia (37°C) and hyperthermia (42°C) were evaluated for each dose level. Seven additional patients were treated with ILuP with 15 and 45 mg melphalan under hyperthermic conditions followed by pulmonary metastasectomy in an extension trial. Pulmonary function tests including spirometry and diffusion capacity were assessed before the procedure and on days 28, 90, 180 and 360 postoperative.
RESULTS: Despite the relative small number of measured lung functions it is evident that a statistically significant decline in DLCO in the first 12 months (p= 0.00-0.05), and of the KCO (p=0.00), FEV1 (p=0.00-0.01), VC (p=0.00) and TLC (p=0.00-0.04) in the first 6 months can be documented after the procedure. This decline in pulmonary function asssessments seems to be partially reversible as is evident from the changes from baseline.
CONCLUSION: Statistically significant and partially reversible decline in all pulmonary function assessments could be documented in the first 6 months after ILuP with melphalan and pulmonary metastasectomy.
CLINICAL IMPLICATIONS: Disturbances in pulmonary functions are observed after treatment with melphalan via ILuP and pulmonary metastasectomy. These are however partially reversible and would not preclude administration of melphalan in ILuP.
DISCLOSURE: Marco Grootenboers, None.