Aim: To define the indications for hyperthermic isolated hepatic perfusion (IHP) in patients with unresectable liver metastases (LM) from colorectal cancer (CRC) with particular focus on IHP's utility as a second-line option for patients whose tumors have progressed following combination systemic chemotherapy treatment. Methods: From June 1994 through July 2005, 120 patients with unresectable CRC LM underwent IHP with melphalan (n = 69), tumor necrosis factor (TNF) (n = 10) or both (n = 41). Hepatic arterial infusion (HAI) with floxuridine started 6-8 weeks post IHP in 46 (38%). Patients were followed for toxicity, radiographic response, and overall survival (OS). Wilcoxon rank-sum and Fisher's exact tests were used to compare parameters by response category; survival and hepatic progression-free survival were calculated by the Kaplan-Meier method. Results: Of 79 males and 41 females, 96 (80%) received prior chemotherapy. There were five (4%) operative/treatment mortalities. There were 69 responses in 114 evaluable patients (61%). Total melphalan dose and combination melphalan/TNF were each associated with response; age, preoperative carcinoembryonic antigen (CEA), prior chemotherapy for established LM, tumor burden, and post-IHP HAI therapy were not. Median overall survival was 17.4 months and 2-year survival was 34%. Factors found to be independently related to survival were preoperative CEA <30 ng/mL and use of post-IHP HAI (P < 0.015). Conclusions: IHP results in marked tumor regression and prolonged survival in patients with CRC LM. Continued development of IHP in this clinical setting is warranted.
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