Isolated hepatic perfusion with extracorporeal oxygenation using hyperthermia, tumour necrosis factor alpha and melphalan

Aims: To determine the toxicity and efficacy of isolated hepatic perfusion with tumour necrosis factor alpha (TNF-alpha) and melphalan (Alkeran(R)) un der mild hyperthermic conditions. Methods: A phase I trial was performed. Eleven patients with unresectable m etastatic malignancies in the liver were pre-treated with 3 x 10(6) U leuko cyte IFN daily 2 days before the perfusion. The liver was isolated and infl ow catheters inserted in the hepatic artery and the portal vein. The hepati c veins were drained via a catheter in the retrohepatic caval vein. The ven ous blood flow from the lower extremities and the splanchnic circulation wa s bypassed to the axillar vein. The liver circuit was perfused with oxygena ted blood and 30-200 mu g TNF-alpha. was added. At 39 degrees C in the live r circuit 0.5 mg/kg melphalan was added and the perfusion was continued for 1 h. Results: Six patients underwent re-operation due to post-operative bleeding . Two patients died of coagulopathy or multiple organ failure within the fi rst post-operative month. Three of six patients with liver metastases from malignant melanoma or leiomyosarcoma showed a partial response while no pat ients with liver metastases from colorectal cancer showed any response. The mean survival time was 20 months, which is within the same range as seen i n previous isolated hepatic perfusion (IHP) studies. Conclusions: IHP with this drug regimen is a method with a considerable tox icity, though it is hard to distinguish between toxicity from TNF-a and tha t from the perfusion procedure itself. The method was not effective in pati ents with colorectal liver metastasis, but the results in melanoma and leio myosarcoma patients warrant further studies.