Hepatocellular carcinoma (HCC) is one of the most common malignancies, with an increasing incidence. With advances in surgical techniques and instrumentation and the development of molecular-target drugs, a number of potentially curative treatments have become available. Management of HCC patients depends on the stage of their tumor. Liver resection remains the first choice for very early-stage HCC, but it is being challenged by local ablative therapy. For early-stage HCC that meet the Milan criteria, liver transplantation still offers a better outcome; however, local ablative therapy can be a substitute when transplantation is not feasible. Local ablation is also used as a bridging therapy toward liver transplantation. HCC recurrence is the main obstacle to successful treatment, and there is currently no effective means of preventing or treating HCC recurrence. Transarterial therapy is considered suitable for intermediate-stage HCC, while sorafenib is recommended for advanced-stage HCC. This stage-based approach to therapy not only provides acceptable outcomes but also improves the quality of life of HCC patients. Because of the complexity of HCC, therapeutic approaches ﾭcusses the current standards and trends in the treatment of HCC.

Disease progression of hepatocellular cancer (HCC) in patients eligible for liver transplantation (LTx) occurs in up to 50% of patients, resulting in withdrawal from the LTx waiting list. Transarterial chemoembolization (TACE) is used as bridging therapy with highly variable response rates. The oral multikinase inhibitor sorafenib significantly increases overall survival and time-to-progression in patients with advanced hepatocellular cancer. The HeiLivCa study is a double-blinded, controlled, prospective, randomized multi-centre phase III trial. Patients in study arm A will be treated with transarterial chemoembolization plus sorafenib 400 mg bid. Patients in study arm B will be treated with transarterial chemoembolization plus placebo. A total of 208 patients with histologically confirmed hepatocellular carcinoma or HCC diagnosed according to EASL criteria will be enrolled. An interim patients' analysis will be performed after 60 events. Evaluation of time-to-progression as primary endpoint (TTP) will be performed at 120 events. Secondary endpoints are number of patients reaching LTx, disease control rates, OS, progression free survival, quality of live, toxicity and safety. As TACE is the most widely used primary treatment of HCC before LTx and sorafenib is the only proven effective systemic treatment for advanced HCC there is a strong rational to combine both treatment modalities. This study is designed to reveal potential superiority of the combined TACE plus sorafenib treatment over TACE alone and explore a new neo-adjuvant treatment concept in HCC before LTx.

Liver Transplantation (LT) is treatment of choice for patients with hepatocellular carcinoma (HCC) within MILAN Criteria. Tumour progression and subsequent dropout from waiting list have significant impact on the survival. Transarterial chemoembolization (TACE) controls tumour growth in the treated HCC nodule, however, the risk of tumour development in the untreated liver is increased by simultaneous release of neo-angiogenic factors. Due to its anti-angiogenic effects, Sorafenib delays the progression of HCC. Aim of this study was to determine whether combination of TACE and Sorafenib improves tumour control in HCC patients on waiting list for LT. Fifty patients were randomly assigned on a 1:1 ratio in double-blinded fashion at four centers in Germany and treated with TACE plus either Sorafenib (n = 24) or placebo (n = 26). The end of treatment was development of progressive disease according to mRECIST criteria or LT. The primary endpoint of the trial was the Time-to-Progression (TTP). Other efficacy endpoints were Tumour Response, Progression-free Survival (PFS), and Time-to-LT (TTLT). The median time of treatment was 125 days with Sorafenib and 171 days with the placebo. Fourteen patients (seven from each group) developed tumour progression during the course of the study period. The Hazard Ratio of TTP was 1.106 (95% CI: 0.387, 3.162). The results of the Objective Response Rate, Disease Control Rate, PFS, and TTLT were comparable in both groups. The incidence of AEs was comparable in the placebo group (n = 23, 92%) and in the Sorafenib group (n = 23, 96%). Twelve patients (50%) on Sorafenib and four patients (16%) on placebo experienced severe treatment-related AEs. The TTP is similar after neo-adjuvant treatment with TACE and Sorafenib before LT compared to TACE and placebo. The Tumour Response, PFS, and TTLT were comparable. The safety profile of the Sorafenib group was similar to that of the placebo group. ISRCTN24081794