Improved regional selectivity of hepatic arterial mitomycin by starch microspheres

Biodegradable starch microspheres, 40 microns in diameter, were administered through hepatic arterial catheters in 16 subjects with primary and metastatic liver tumors. These microspheres temporarily obstruct blood flow at the precapillary arteriole (microcirculation) level. Our study was undertaken to determine whether such occlusion would enhance hepatic deposition of, and thereby decrease systemic exposure to, simultaneously administered hepatic arterial mitomycin C (mito). When mito (10 mg/m2 over 1 min) was given with 90 X 10(6) microspheres (10 subjects), there was a 17% to 70% reduction in systemic mito exposure. When mito (10 mg/m2 over 1 min) was given with 36 X 10(6) microspheres (six subjects), there was a 15% to 60% reduction in systemic exposure, which may correlate with dose-dependent shunting (8% to 29%) through the liver to the lung (and hence to the systemic circulation), attributed to the starch microspheres. No life-threatening myelosuppression was noted; hepatic toxicity consisted of transient pain and elevation of liver enzymes.