Angiogenic Blockade and Radiotherapy in Hepatocellular Carcinoma

Abstract

We report our preliminary experience of combining sunitinib and helical tomotherapy in patients with advanced HCC. Records of patients with advanced hepatocellular carcinoma (HCC) treated with helical tomotherapy and sunitinib after radiation therapy (RT) from March 2007 to August 2008 were retrospectively reviewed. We report acute toxicities, radiologic response, serial alpha-fetoprotein (AFP) kinetics, and survival. Of 23 evaluable patients, 60% had >or=2 hepatic lesions, extrahepatic disease was present in 5 (21.7%), and all received 2 tablets (25 mg) of sunitinib at least 1 week before, during, and 2 weeks after RT. Thirteen patients continued maintenance sunitinib after RT until disease progression. Hypofractionated RT with a median target dose of 52.5 Gy/15 fractions was delivered. An objective response was achieved in 74% of patients. The 1-year survival rate was 70%, with median survival of 16 months. Multivariate analysis showed that maintenance sunitinib was the most significant factor for survival. The time to progression was 10 months in the maintenance group compared with 4 months in the control group. Eighteen out of 21 patients with elevated AFP (85.7%) had >or=50% decline of AFP within 2 months after RT. There were three episodes of upper gastrointestinal bleeding and one episode of pancreatitis; 10 patients had >or=Grade 2 elevation of liver enzymes, and 15 had >or=Grade 2 thrombocytopenia. These preliminary results suggest that sunitinib and helical tomotherapy yield high Response Evaluation Criteria in Solid Tumors (RECIST) and AFP response rates in advanced HCC with an acceptable safety profile. Maintenance sunitinib after RT potentially prolongs survival. A randomized trial is warranted.