Floxuridine Hepatic Arterial Infusion Associated Biliary Toxicity Is Increased by Concurrent Administration of Systemic Bevacizumab

Abstract

Systemic bevacizumab (Bev) was added to hepatic arterial infusion (HAI) floxuridine (FUDR)-based chemotherapy in three studies in an attempt to improve outcomes. A specific review of biliary toxicity was carried out. This analysis included 203 patients from three prospective studies. The first (study A) was an adjuvant study after liver resection of colorectal metastases in which patients received HAI and systemic chemotherapy (Sys) with or without Bev. Study B comprised unresectable colorectal patients who received HAI and Sys plus Bev. Study C included patients with unresectable cholangiocarcinoma or hepatocellular carcinoma who received HAI plus systematic Bev. The outcome and toxicity of patients in studies B and C were compared with historical controls. In all three studies, the incidence of hyperbilirubinemia and biliary stent placement within 1year of treatment was increased with the addition of Bev. In the no-Bev versus Bev groups, the placement of biliary stents was as follows: study A, 0 of 38 versus 4 of 35 patients (p=0.05); study B, 0 of 49 versus 3 of 24 (p=0.06); and study C, 0 of 34 versus 3 of 22 (p=0.15). Elevation in bilirubin was noted in the no-Bev versus Bev groups: study A, 0 of 38 versus 5 of 35 patients (p=0.02); study B, 1 of 49 versus 7 of 24 (p=0.005); and study C, 2 of 34 versus 5 of 22 (p=0.10). The addition of Bev did not seem to be associated with improved progression-free or overall survival. The addition of Bev to HAI FUDR resulted in increased biliary toxicity in three separate studies. Although the sample sizes were small, there was no evidence of improved PFS or OS with the addition of Bev. Bev should not be combined with HAI FUDR.