Preclinical toxicity study of streptozocin infused into the internal carotid artery of dogs and baboons.

Abstract

Mature male and female dogs (10) and male baboons (4) were each given a single dose of streptozocin (STZ) (1000 mg/m2) by infusion directly into the left internal carotid artery over a two-hour time period. Serial hematology and serum chemistry profiles and physical observations were made, the animals necropsied at varying times after dosage, and the major organs examined histologically. In dogs, severe weight loss, neutrophilia, electrolyte disturbances, decreased liver function, diabetes and decreased serum amylase levels were the major toxicities. In baboons, weight loss, hypoglycemic coma, diabetes, decreased liver function and electrolyte disturbances were observed. While systemic toxicities were severe in both animal species, central nervous system toxicity was minimal. Cerebral toxicities consisting of edema in two dogs, and focal necrosis in one dog were observed histopathologically. No cerebral toxicity occurred in baboons. Based upon these findings, a phase I clinical trial of intra-arterial (internal carotid artery) STZ in patients with primary/metastatic brain tumors would appear feasible.