Isolated limb perfusion with tumour necrosis factor alpha (TNF-α) and melphalan is well tolerated and highly effective in irresectable sarcoma and melanoma. No data are available on isolated hepatic perfusion (IHP) with these drugs for irresectable hepatic malignancies. This study was undertaken to assess the feasibility of such an approach by analysing hepatic and systemic toxicity of IHP with TNF-α with and without melphalan in pigs. Ten healthy pigs underwent IHP. After vascular isolation of the liver, inflow catheters were placed in the hepatic artery and portal vein, and an outflow catheter was placed in the inferior vena cava (IVC). An extracorporeal veno-venous bypass was used to shunt blood from the lower body and intestines to the heart. The liver was perfused for 60 min with (1) 50 μg kg-l TNF-α (n = 5), (2) 50 μg kg-1 TNF-α plus 1 mg kg-1 melphalan (n = 3) or (3) no drugs (n = 2). The liver was washed with macrodex before restoring vascular continuity. All but one pigs tolerated the procedure well. Stable perfusion was achieved in all animals with median perfusate TNF-α levels of 5.1 ± 0.78 x 106 pg ml-1 (± s.e.m). Systemic leakage of TNF-α from the perfusate was consistently < 0.02%. Following IHP, a transient elevation of systemic TNF-α levels was observed in groups 1 and 2 with a median peak level of 23 ± 3 x 103 pg ml-1 at 10 min after washout, which normalized within 6 h. No significant systemic toxicity was observed. Mild transient hepatotoxicity was seen to a similar extent in all animals, including controls. IHP with TNF-α with(out) melphalan in pigs is technically feasible, results in minimal systemic drug exposure and causes minor transient disturbances of liver biochemistry and histology.
|Tijdschrift||British Journal of Cancer|
|Nummer van het tijdschrift||10|
|Status||Gepubliceerd - 1997|