Intraarterial versus intravenous adriamycin in the rabbit Vx-2 tumor system

Intraarterial (IA) chemotherapy can theoretically result in a high tissue level of the drug with reduced systemic toxicity compared with intravenous (IV) administration. The authors compared these two modes of therapy using Adriamycin (doxorubicin) in the rabbit Vx-2 tumor system. Vx-2 was implanted in hind limb muscle, and silastic catheters were placed in the jugular vein and femoral artery. Nuclear imaging of technetium-99m-labeled autologous erythrocytes in nine animals was used to measure the kinetics of tumor blood flow. Presence of tumor increased flow through the involved limb up to threefold. One minute following injection there was no difference in concentration of 99mTc in tumor whether labeled cells were introduced IA or IV. Twelve rabbits received IA (N = 6) or IV (N = 6) Adriamycin (3 mg/kg), while eight animals received normal saline IA or IV as controls. Tumor progressed in all control rabbits, whereas there was an objective or complete response in 83% of animals receiving Adriamycin. One hundred percent of those treated IA responded compared with 67% for IV (P = 0.04). Median time to initial response in animals treated IA was 7 days versus 21 days for those treated IV (P = 0.02). Thus, IA Adriamycin achieves a more complete and more rapid response than the drug given IV. This occurs despite a large tumor blood flow and rapid equilibration using both methods.