Efficacy and Safety of Sorafenib in Advanced Hepatocellular Carcinoma Under Daily Practice Conditions

Abstract

Sorafenib has recently been shown to be effective for the treatment of advanced hepatocellular carcinoma in randomized controlled trials. Here, we report the experience with sorafenib in 25 patients with advanced HCC under daily practice conditions. Tolerance to sorafenib was acceptable and side effects were manageable, although the ECOG performance status was reduced in all patients. The most prevalent grade 2/3 side effects were fatigue (40%) and diarrhea (24%), and withdrawal from therapy occurred in 29% of patients. Disease stabilization was documented in 60% of patients. The median treatment time was 2.7 months and overall survival was 11.0 months. No significant serum alpha-fetoprotein decline was noted at the time of the first radiological control in a subgroup of patients with baseline levels >50 ng/ml who achieved stable disease. In conclusion, in daily practice sorafenib is safe and disease stabilization can be achieved in the majority of patients. However, intolerance to sorafenib can affect treatment adherence substantially.

Activating oxidative phosphorylation by a pyruvate dehydrogenase kinase inhibitor overcomes sorafenib resistance of hepatocellular carcinoma

“…Sorafenib is the only drug that has been shown to prolong survival of patients with HCC in randomised controlled trials; however, its modest efficacy and high rate of intolerance limit the utility of sorafenib in the general population of HCC patients (Welker et al , 2010; Morimotoo et al , 2011). To date, there are no reliable predictive biomarkers for sorafenib sensitivity that can be used to guide the personalised use of sorafenib.…”

mTOR inhibitors and sorafenib for recurrent heptocellular carcinoma after orthotopic liver transplantation

“…These data form the current rational to switch patients with recurrent HCC after liver transplantation from calcineurin inhibitors to mTOR inhibitors like sirolimus or everolimus, and additionally to start sorafenib. However, even in patients without liver transplantation, the toxicity of sorafenib can severely impact quality of life [9,10] and up to now only anecdotal data on the use of sorafenib after liver transplantation are available [2]. Although sorafenib and mTOR inhibitors have different targets, side-effects of both drugs overlap (e.g.…”

Antitumor effect of vascular endothelial growth factor inhibitor sunitinib in preclinical models of hepatocellular carcinoma

“…The results from preclinical studies using xenograft models support the concept that inhibition of blood vessel development will stop or significantly limit oxygen and nutrient supply to the tumor, causing tumor cell starvation and eventually apoptosis [16,17]. However, clinical trials with antiangiogenic treatments have led to survival benefits in HCC patients [18], with the exception of sorafenib, which has been shown to lead to a significant improvement in overall survival in patients with HCC, suggesting that this class of agents may be effective in the treatment of HCC [1].…”