Isolated hepatic perfusion for unresectable hepatic metastases from colorectal cancer

Background. Unresectable colorectal liver metastases are a significant clin ical problem. Isolated hepatic perfusion (IHP) is a regional treatment tech nique that delivers high dose chemotherapy, biologic agents, and hypertherm ia via a completely isolated vascular recirculating perfusion circuit as a means of regionally treating liver tumors. This stud presents our results o f IHP with tumor necrosis factor (TNF) plus melphalan or IHP with melphalan alone followed by infusional floxuridine (FUDR) and leucovorin in patients with advanced or refractory unresectable hepatic colorectal metastases. Methods. Fifty-one patients with unresectable colorectal hepatic metastases underwent a 60-minute IHP with 1.5 mg/kg melphalan and hyperthermia (39 de greesC to 40 degreesC). Thirty-two patients received IHP with 1 mg TNF with melphalan and 19 patients had IHP with melphalan alone followed by monthly hepatic intra-arterial infusional (HAI) FUDR (0.2 mg/kg/day) and leucovori n (15 mg/M-2/day) for 14 days monthly for up to 12 months. Twenty-six patie nts failed 1 or more previous treatment regimens for established hepatic me tastases and 27 had greater than 25% hepatic replacement (PHR) by tumor. Pa tients were monitored for response, toxicity, and survival. Results. There was 1 perioperative death (2%), and only 2 patients (4%) had measurable perfusate leak during IHP (both less than 4%). In the 32 patien ts treated with IHP alone there were no detectable systemic TNF or melphala n levels during per fusion. The overall objective radiographic response rat e (all partial [PR]) was 76% (38 of 50 assessable patients) with a median d uration of 10.5 months (range, 2 to 21 months). Twenty-four of 31 patients (77%) had a PR after IHP alone and 14 of 19 (74%) after IHP with postperfus ion HAI. Median duration of response was 8.5 months after IHP alone and 14. 5 months after IHP and HAI; median survival was 16 and 27 months, respectiv ely. There were 18 PRs in 26 patients (69%) whose prior therapy had failed and 18 PRs in 27 patients (67%) with PHR of 25 or greater. Conclusions. IHP can be performed with acceptability low morbidity and has significant antitumor activity in patients with unresectable hepatic metast ases from colorectal cancer including those with refractory disease or PHR of 25 or greater. HAI appears to prolong the duration of response after IHP , and this combined treatment strategy deserves additional clinical evaluat ion as a therapeutic modality in this setting.