Moreover, one of the selleckbio challenges in the treatment with sorafenib is the difficulties in assessing tumor response by traditional response criteria. The pivotal trial by Llovet et al. reported a very modest response rate of only 2% [4]. The lack of a correlation between objectively observed response and clinical benefit complicates treatment evaluation and clinical decision making [7]. A clinical improvement in patients’ symptoms may not be expected, as no significant difference between time to symptom worsening has been observed in sorafenib-treated patients compared to placebo [4]. Recent studies indicate that an early decline in serum ��-fetoprotein (��FP) may be a predictive marker for treatment response to targeted therapies in advanced HCC [7, 8].

In the current study we evaluate the efficacy and tolerability of sorafenib in an unselected patient population as they present in every day clinical practice. Furthermore we explore the role of ��FP in treatment evaluation and its correlation to survival outcome.2. Materials and Methods2.1. PatientsAccess to sorafenib was made available in August 2007 through a program under the Danish National Board of Health. All patients considered for sorafenib were reviewed by a panel of experts appointed by the National Board of Health and referred to one of two centrs designated to treat HCC patients with sorafenib in Denmark.

A common set of criteria for the selection of patients were used by the two centres: advanced hepatocellular carcinoma diagnosed according to the criteria of EASL [9], not amendable for locoregional treatment (including transcatheter arterial chemoembolization, radio frequency ablation (RFA), and surgery), ECOG PS 0�C2, CP A or B, and no Drug_discovery substantial co-morbidity (uncontrolled cardio- or cerebrovascular disease, recent bleeding episodes, or active ulcer disease).All patients had a dynamic three-phase CT scan performed at baseline as well as an electrocardiogram, blood pressure measurement, blood samples including haematological values, liver biochemistry, and serum ��FP.2.2. TreatmentSorafenib was administered at a dose of 800mg daily. However, weak or elderly patients started at a reduced dose of 400mg daily, with the possibility of dose escalation. Dose reduction and treatment delay were performed according to the recommendations in the summary of product characteristics [2].Treatment was continued until radiological or clinical progression, unacceptable toxicity, death, or patient refusal. Patients were seen every 4 weeks for toxicity management and clinical assessment. Response evaluation was performed every 12 weeks and included a CT-scan, liver biochemistry, and serum ��FP. 2.3.