Micro- and macroarteriolar blockade of hepatocellular carcinoma (HCC): Ramping up the dose of sorafenib over two weeks before hepatic arterial chemoembolization (HACE) for liver cancer.

Abstract

472 Background: Multiple sessions of hepatic artery chemo-embolization (HACE) are usually necessary to achieve partial or complete ablation of a hepatoma (HCC). Blocking the pro-angiogeneic environment and re-establishment of tumor microvasculature with the tyrosine kinase inhibitor sorafenib administered prior to HACE may enhance tumor necrosis and possibly patient survival. Methods: Twenty patients with inoperable HCC were subject to 2 weeks of sorafenib, followed by HACE using Adriamycin and mitomycin C. The first 10 patients were treated with a sorafenib 400 mg twice a day. The second 10 patients had their dose of sorafenib ramped up from 200 mg twice a day to 400 mg twice a day over 1-2 weeks according to tolerability. Patients were continued on sorafenib during as many HACE procedures needed to achieve no evidence of enhancement on multi-phase imaging. Results: The mean length of treatment for the ramped up group was significantly longer that the non-ramped up group as shown in table 2. (3.90 vs 3.05, N < 0.05). There was no significant difference in survival, nor adverse events between groups. Three patients (5, 12, 13) ultimately went on to receive a liver transplant. Conclusions: Use of sorafenib prior to HACE is feasible and safe. Ramping up the dose over 2 weeks allows more patient to stay on treatment longer. Further studies are needed to determine how best to combine sorafenib with HACE in order to increase survival and eligibility of patients to be listed for liver transplant. Clinical trial information: NCT00949182.