Isolated hepatic perfusion with extracorporeal oxygenation using hyperthermia, tumour necrosis factor alpha and melphalan.
OBJECTIVE
To determine the toxicity and efficacy of isolated hepatic perfusion with tumour necrosis factor alpha (TNF-alpha) and melphalan (Alkeran) under mild hyperthermic conditions.


METHODS
A phase I trial was performed. Eleven patients with unresectable metastatic malignancies in the liver were pre-treated with 3 x 10(6) U leukocyte IFN daily 2 days before the perfusion. The liver was isolated and inflow catheters inserted in the hepatic artery and the portal vein. The hepatic veins were drained via a catheter in the retrohepatic caval vein. The venous blood flow from the lower extremities and the splanchnic circulation was bypassed to the axillar vein. The liver circuit was perfused with oxygenated blood and 30-200 microg TNF-alpha was added. At 39 degrees C in the liver 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 first post-operative month. Three of six patients with liver metastases from malignant melanoma or leiomyosarcoma showed a partial response while no patients with liver metastases from colorectal cancer showed any response. The mean survival time was 20 months, which is within the same range as seen in previous isolated hepatic perfusion (IHP) studies.


CONCLUSIONS
IHP with this drug regimen is a method with a considerable toxicity, though it is hard to distinguish between toxicity from TNF-alpha and that from the perfusion procedure itself. The method was not effective in patients with colorectal liver metastasis, but the results in melanoma and leiomyosarcoma patients warrant further studies.
Lindnér
P
P
Department of Surgery, Sahlgrenska University Hospital, Göteborg, Sweden.
Fjälling
M
M
Hafström
L
L
Kierulff-Nielsen
H
H
Mattsson
J
J
Scherstén
T
T
Rizell
M
M
Naredi
P
P
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D010478:Chemotherapy, Cancer, Regional Perfusion; D015179:Colorectal Neoplasms / Q000473:pathology; D015199:Extracorporeal Membrane Oxygenation; D005260:Female; D006499:Hepatic Artery; D006801:Humans; D006979:Hyperthermia, Induced; D007890:Leiomyosarcoma / Q000556:secondary; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000556:secondary / Q000628:therapy*; D008297:Male; D008545:Melanoma / Q000556:secondary; D008558:Melphalan / Q000627:therapeutic use*; D008875:Middle Aged; D011859:Radiography; D014409:Tumor Necrosis Factor-alpha / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D014409:Tumor Necrosis Factor-alpha; D008558:Melphalan