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Regional Infusion of Vinblastine and Hydrogen Peroxide in Tumor-bearing Rats¹

Section of Neurological Surgery, Department of Surgery, Indiana University Medical Center, Indianapolis, Indiana

The present investigation was undertaken to evaluate the effectiveness of regional arterial infusion of vinblastine on a predictable experimental tumor and to determine whether the response to treatment might be potentiated by concomitant regional hyperoxygenation with hydrogen peroxide. Sprague-Dawley rats received single intra-aortic infusions of vinblastine (0.5 mg/kg) and hydrogen peroxide (3 mg/animal) and a combination of both compounds 1 week and 1 day after inoculation of a suspension of Walker 256 carcinosarcoma in the thigh muscles. Vinblastine partially inhibited subsequent growth of the established solid tumors. However, treatment 1 week after implantation did not prove therapeutic since the animals died from metastatic disease without prolongation of survival.

When regional arterial infusion of vinblastine was performed 1 day after inoculation of the tumor, 40% of the animals became free of the tumor and lived indefinitely. This salutary effect was reduced by half when vinblastine was given in conjunction with hydrogen peroxide. In the animals that ultimately died from extension of the tumor after intra-arterial vinblastine injections, survival was significantly increased, with inhibition of local tumor growth and the rapid metastatic spread of this neoplasm. Hydrogen peroxide alone was not effective against this tumor, and rather than enhancing the therapeutic action of vinblastine, adjunctive use of hydrogen peroxide made treatment more lethal (the toxic mortality was 21–30%).

¹ This work was supported by USPHS Grant CA-06145 from the NIH, Bethesda, Maryland.

Received 4/ 1/65.