CANCER RESEARCH Regional Infusion of Vinbiastine and Hydrogen Peroxide in Tumor-bearing Rats'

When vinblastine was injected into the internal carotid artery of individuals with intracranial neopla.sms, it usu ally caused a prompt oculocutaneous toxicity. Though less severe, the direct local effects simulated the histo toxicity of the alkylating agents (6, 7, 9, 12, 13). Intra arterial infusion of hydrogen peroxide was reported to increase selectively the uptake of several radioactive corn pounds in cerebral tumors (3). When vinblastine was oxidized in vitro by the addition of hydrogen peroxide in excess, the anoxide products in 1 experiment had a biologic activity comparable to the parent alkaloid base (M. Gorman, Lilly Research Laboratories, personal communi cation). These observations prompted the following em pirical inquiry into the possible usefulness of hydrogen peroxide as a potentiator of the response to regional ar terial infusion of vinblastine. Underlying mechanisms are