Background. Unresectable colorectal liver metastases are a significant clinical problem. Isolated hepatic perfusion (IHP) is a regional treatment technique that delivers high dose chemotherapy, biologic agents, and hyperthermia via a completely isolated vascular recirculating perfusion circuit as a means of regionally treating liver tumors. This study presents our results of 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°C to 40°C). 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 leucovorin (15 mg/M2/day) for 14 days monthly for up to 12 months. Twenty-six patients failed 1 or more previous treatment regimens for established hepatic metastases and 27 had greater than 25% hepatic replacement (PHR) by tumor. Patients 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 patients treated with IHP alone there were no detectable systemic TNF or melphalan levels during perfusion. The overall objective radiographic response rate (all partial [PR]) was 76% (38 of 50 assessable patients) with a median duration 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 postperfusion 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, respectively. 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 acceptably low morbidity and has significant antitumor activity in patients with unresectable hepatic metastases 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 evaluation as a therapeutic modality in this setting.
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