Hepatic arterial infusion of recombinant platelet factor-4 suppresses metastases to the lungs from tumors implanted into the livers of rabbits.

Abstract

This study evaluated the toxicity (Part I) and antitumor effects (Part II) associated with hepatic arterial infusion of recombinant platelet factor-4 (rPF4), an antiangiogenic protein. Healthy rabbits (Part I) and rabbits with tumors implanted in their livers (Part II) received saline or rPF4 via hepatic arterial infusion. Three saline-receiving and four rPF4-receiving animals died 2-3 days postinfusion from gastroduodenal thromboembolism. The remaining animals were necropsied 3, 7, 10, or 14 days postinfusion. Blood analyses and hepatic angiography were performed before infusion and at the time of sacrifice. In Part I, focal coagulation necrosis of the hepatic parenchyma was observed in 1 of 11 rabbits that received saline and in 6 of 10 that received rPF4. In Part II, hepatic arterial infusion of rPF4 had no effect on growth of the implanted liver tumors. However, the protein significantly reduced the incidence of lung metastasis. Intraarterial infusion of rPF4 significantly reduced the incidence of lung metastasis. Nonheparin systemic anticoagulation may be needed during catheterization and infusion procedures to prevent thromboemboli.