Early antiangiogenic activity of bevacizumab evaluated by computed tomography perfusion scan in patients with advanced hepatocellular carcinoma

BACKGROUND: Hepatocellular carcinoma (HCC) is a highly vascularized tumor with a poor prognosis. In a phase II study that combined bevacizumab with gemcitabine and oxaliplatin in advanced HCC, we examined computed tomography perfusion (CTp) scan parameters as surrogate markers of angiogenesis after bevacizumab administration. METHODS: HCC patients received bevacizumab alone i.v. at 10 mg/kg on day 1 during cycle 1. CTp scanning was performed at baseline and days 10-12 to assess changes in tissue blood flow (BF), blood volume (BV), mean transit time (MTT), and permeability surface area product (PS). RESULTS: Compared with baseline, a significant decrease in the estimated tumor perfusion parameters including BF, BV, and PS and an increase in MTT were seen on days 10-12 following bevacizumab administration alone. Patients with progressive disease had lower baseline MTT values and a higher percent increase following bevacizumab administration than those with stable disease or partial responses. CONCLUSIONS: Bevacizumab induced a significant decrease in tumor BF, BV, and PS and an increase in MTT by CTp scan in HCC. Baseline and percent change in MTT following bevacizumab administration correlated with clinical outcome, whereas BF, BV, and PS did not.