Pharmacodynamic assessment of the anti-angiogenic and anti-vascular properties of bevacizumab by magnetic resonance imaging in metastatic colorectal carcinoma (CRC)

Abstract

3546 Background: Addition of bevacizumab to FOLFOX-4 prolongs progression free and overall survival in patients with metastatic CRC. Bevacizumab reduces tumor blood flow, so may impair delivery of subsequent cytotoxic chemotherapy. We present the first data that describe in detail the temporal anti-angiogenic and anti-vascular effects of bevacizumab. Methods: DCE-MRI and volumetrics were used to evaluate tumor pharmacodynamics and growth inhibition in ten patients with newly diagnosed CRC liver metastases. Patients were imaged at baseline (twice), 4 hours after single agent 10mg/kg bevacizumab, and at days 3, 8, and 12. An extended Tofts model was applied to allow calculation of plasma volume (vp) and Ktrans. Results: 34 tumors were identified. Significant reductions in Ktrans and vp were detected within 4 hours, were maximal at day 3 and persisted until day 8 (all p<0.001). The proportion of enhancing voxels was also reduced within 4 hrs (p=0.007) and persisted to day 12 (p<0.001). Mean tumor volume exhi...