Phase II multicenter clinical trial of isolated lung perfusion (ILuP) with melphalan (MN) in patients (pts) with resectable lung metastases (LM).

Abstract

7534 Background: Five-year overall survival (OS) of pts undergoing surgical resection of LM from colorectal cancer (CRC) and sarcoma remains low [20-50%]. Local recurrence rate is high, even after complete surgical resection [48-66%] (Pastorino et al, 1997). Combined modality therapy is currently evaluated. ILuP allows the delivery of high-dose locoregional chemotherapy without systemic exposure. In a previous phase I study maximum tolerated dose of MN was found to be 45mg at a perfusion temperature of 37°C (Grootenboers et al, 2007). Methods: From 2006 to 2011 50 pts, 28 male, median age 57 years [15-76], with LM from CRC [n=30] or sarcoma [n=20] were included in a phase II clinical trial conducted in 4 cardiothoracic surgical centers. In total, 62 ILuP procedures were performed, 12 bilaterally, followed by resection of all palpable LM. Survival was calculated according to the Kaplan-Meier method. Results: Operative mortality was 0%, 90-day morbidity was mainly cardiac [grade 3: 2%] and respiratory [grade 3: 29%, grade 4: 2%]. After a median follow-up of 24 months [3-63 mos] 18 pts died, 2 without recurrence. Seven pts [14%] had their initial recurrence in the perfused lung. Initial progressive disease outside the perfused lung occurred in 23 pts [46%]; contralateral, non-perfused lung 10, liver 3, brain 2, primary site 1 and other location 7. OS and disease-free survival (DFS) are shown in table 1. Lung function data showed a decrease in FEV1 and DLCO of 21.6% and 25.8% after 1 month, and 10.4% and 11.3% after 12 mos, respectively, compared to preoperative values. Long-term quality of life evolution after ILuP and lung metastasectomy was comparable with a standard lung metastasectomy by thoracotomy in one participating center (Balduyck et al, 2012). Conclusions: Compared to historical series of LM resection without ILuP favorable results are obtained in terms of local control without long-term adverse effects. These data support the further investigation of ILuP as additional treatment in pts with resectable LM from CRC or sarcoma. Clinical trial information: 2006-002808-34. [Table: see text]