Bevacizumab in hepatocellular carcinoma (HCC) in patients without metastasis and without invasion of the portal vein

Abstract

4122 Bevacizumab in hepatocellular carcinoma (HCC) in patients without metastasis and without invasion of the portal vein Background: HCC is a vascular tumor; angiogenesis contributes to pathogenesis. Bevacizumab (anti-VEGF) delays progression in colon cancer and its effect may be dose-dependent. VEGF-inhibition has not been previously attempted in cirrhosis. Methods: We enrolled patients with unresectable HCC to bevacizumab at 5mg/kg or 10mg/kg every 14 days to assess safety and preliminary efficacy. Inclusion criteria were BR < 3.0mg/dl, transaminases 75K and PT within 4 seconds of normal. Additional criteria included no history of gastrointestinal bleed, myocardial infarction, stroke, or condition requiring antiplatelet or antithrombotic therapy. Results: An initial safety assessment indicates that 10 of 11 patients treated for at least 8 weeks tolerated bevacizumab at 5mg/kg with minimal toxicity. Two patients had serious esophageal bleeding which was likely secondary to progression of HCC and liver disease (although contribution of drug to these events cannot be excluded). The protocol has been modified to identify and treat esophageal varices prior to enrollment. Three patients treated at 10mg/kg have undergone at least 8 weeks of therapy with minimal toxicity (grade 1 fatigue, abdominal pain and diarrhea). For the first 13 patients evaluable for efficacy, 11 have had confirmed response or stability. Two patients had disease progression at less than 4 months. Two patients had partial responses, one with eventual progression at 11.3 months. For the 9 patients with stable disease, 6 had eventual progression at 5.5, 6.5, 6.5, 6.7, 7.2, and 7.6 months. Three others have ongoing stability at 3.5+, 3.9+, and 12.7+ months. At least four of the patients with confirmed response/stability had documented rapidly-progressing disease in the months before receiving therapy. Conclusions: Bevacizumab can be given safely at both 5mg/kg and 10mg/kg in HCC patients with localized, unresectable HCC, preserved liver function and no significant esophageal varices. Preliminary results suggest significant disease-modifying effect, including 6+ month stability in patients with prior rapid growth. No significant financial relationships to disclose.