Phase I evaluation of sorafenib (SOR) and bevacizumab (BEV) as first-line therapy in hepatocellular cancer (HCC): North Central Cancer Treatment Group trial N0745.

4116 Background: HCC tumors are highly vascular and over express VEGF. The monoclonal antibody BEV and the oral multi-kinase inhibitor SOR inhibit VEGF-induced angiogenesis and the associated Ras/Raf/MEK/ERK signaling pathway. It is hypothesized that SOR will complement the mode of action of BEV by more fully blocking VEGF signaling. Methods: Eligibility included measurable locally advanced or metastatic HCC not amenable for surgery or liver transplant (BCLC-C), Child Pugh A or B7, esophageal varices if treated ≥ 6 mos, and acceptable blood chemistries. Patients with mixed cholangiocarcinoma/HCC were ineligible. Treatment doses/schedule appears in the table. The phase I starting dose level (0) was: BEV 1.25 mg/kg d1 and 15 plus SOR 400 mg BID d1-28. Results: 17 patients aged 18-79 (mean 62.4 yrs) were enrolled; 14 were male. A majority of patients presented with ascites (71%). Baseline characteristics included cirrhosis (41% of patients), prior RT (12%), prior chemoembolization (6%), and vascular invasion...