Hepatic arterial streptozocin: a clinical pharmacologic study in patients with liver tumors

Hepatic arterial infusions of streptozocin (STZ) were compared with peripheral venous infusions administered for 3 h at a dose rate of 0.5 or 1.0 g/m2 . h in five patients with liver-predominant neoplastic disease. Peripheral venous plasma STZ levels were measured during and for 3 h after completion of all infusions. Steady-state was achieved at 2 h and the elimination half-life was 35-40 min, the total body clearance was 400 ml/min, and the volume of distribution of STZ was 20-22 liters in these patients. Comparison of steady-state drug levels demonstrated minimal hepatic extraction (mean 5%). Assuming a hepatic arterial blood flow of 100-200 ml/min with a total body clearance of 400 ml/min, hepatic arterial administration of STZ can be expected to result in a three- to sixfold greater exposure of tumor in the liver compared with the intravenous route. Toxicity was minimal and two patients had evidence of response.