Targeting the Tumor Vasculature: Enhancing Antitumor Efficacy through Combination Treatment with ZD6126 and ZD6474

Abstract

Background: The antitumor efficacy of combination therapy of the vascular disrupting agent ZD6126 and antiangiogenic agent ZD6474 was evaluated in the models of human colorectal (HT29) and ovarian carcinoma (OW1). Materials and Methods: HT29 and OW1 xenograft-bearing mice were treated with ZD6126 and ZD6474 either alone or in combination. ZD6126 therapy consisted of three doses of 100 mg/kg administered 1, 3 and 5 days after the tumor reached the starting size. ZD6474 was administered daily at a dose of 25 mg/kg on days 1-5. Results: ZD6126 and ZD6474 treatment alone only resulted in modest tumor growth delay. However, significantly enhanced antitumor effects were observed in the combinaion treatment. Conclusion: The combination of the vascular disrupting with the antiangiogenic agent led to significant enhancement of antitumor efficacy in HT29 and OW1 human tumor models. Such combination therapy may have significant therapeutic benefit even in tumors insensitive to either treatment alone.