Abstract 2246: Sorafenib in patients with hepatocellular cancer before liver transplantation – first safety data of the prospective, randomized, double-blind, multi-center, phase III HeiLivCa trial [ISRCTN24081794]
Authors: Hoffmann Katrin , Ganten Tom , Glimm Hanno , Radeleff Boris , von Kalle Christof , Jäger Dirk , Büchler Markus W. , Schemmer Peter 
Published: June 2012

Abstract
Background: The efficacy of locoregional bridging therapies for patients with hepatocellular carcinoma (HCC) awaiting liver transplantation (LT) remains controversial. Tumor progression and drop out from the waiting list have significant impact on the survival. There is strong evidence to support the effectiveness of sorafenib in extending the time to progression of HCC. However, concerns have been raised that the antiangiogenic effect of sorafenib may be associated with a potentially higher risk of postsurgical complications. The HeiLivCa trial investigates sorafenib as neoadjuvant therapy before LT.
Methods: In the HeiLivCa multi-centre, phase III, double-blind, placebo- controlled trial, patients with HCC awaiting LT who had no previous treatment are assigned to receive either transarterial chemoembolization (TACE) plus sorafenib (at a dose of 400mg twice daily) or TACE plus placebo. All patients had measurable disease according to RECIST without evidence of radiologically definable major vascular invasion or extrahepatic metastases, ECOG performance status 0 or 1, adequate liver function with bilirubin &lt;3mg/dl, prothrombin time less than 1.5 times the upper limit of normal, and adequate renal as well as haematological function. The safety data of the first 21 consecutive patients were analyzed without unblinding of the study treatment.
Results: Of 21 patients (95% male; median age 57 years), 71% had Child-Pugh class A and 29% Child-Pugh class B liver cirrhosis. 57% of patients had solitary, 38% 2-3 HCCs and the median number of applied TACE treatments was three.ECOG performance status was 0 in 61% of patients. The neo-adjuvant treatment was generally well tolerated. The overall incidence of treatment-related adverse events was 60%. There were no TACE associated adverse events. The most commonly reported treatment-emergent non-haematological adverse events were hand-foot-skin syndrome (15%), fatigue (20%) and diarrhoea (20%). Grade 3 laboratory abnormalities occurred in 43% of patients, with hyperbilirubinaemia (24%), GGT elevation (19%), ASAT / ALAT elevation (10%). There were no grade 4 drug-related adverse events in any of these categories. The overall incidence of adverse events was similar in Child-Pugh class A and B patients. No increased risk of bleeding or wound healing complications was detectable in patients undergoing LT. The overall 30-day morbidity rate after LT was 28%.
Conclusion: In patients with early HCC awaiting LT combined neo-adjuvant treatment with sorafenib seems to be safe and shows manageable toxicity. The risk for postsurgical complications after LT was not increased. Patient recruitment in the HeiLivCa trial is ongoing.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2246. doi:10.1158/1538-7445.AM2011-2246