Efficiency and Side Effects of Sorafenib Therapy for Advanced Hepatocellular Carcinoma: A Retrospective Study by the Anatolian Society of Medical Oncology

Abstract

Background: Inoperable and metastatic hepatocellular carcinoma (HCC) is associated with a poor prognosis and low chemotherapeutic efficiency. Sorafenib is an oral multi-kinase inhibitor exerting its effects via the RAF/ MEK/ERK pathway, vascular endothelial growth factor receptor (VEGFR) and platelet derived growth factor receptor beta (PDGFR-β) tyrosine kinases. Randomized studies have shown a significant contribution of sorafenib to life expectancy and quality of life of cancer patients. The aim of the present study is to evaluate the efficacy and side effects of sorafenib therapy in Turkey. Materials and Methods: Data for 103 patients (82 males, 21 females) receiving sorafenib therapy in 13 centers from February 2008 to December 2012 were evaluated. Median age was 61 years and median ECOG performance status was 1 (range: 0-2). 60 patients (58%) had hepatitis B, 15 patients (15%) had hepatitis C infection and 12 patients (12%) had a history of alcohol consumption. All of the patients had Child scores meeting the utilization permit of the drug in our country (Child A). Results: A total of 571 cycles of sorafenib therapy were administered with a median of four per patient. Among the evaluable cases, there was partial response in 15 (15%), stable disease in 52 (50%), and progressive disease in 36 (35%). Median progression-free survival was 18 weeks and median overall survival was 48 weeks. The dose was reduced only in 6 patients and discontinued in 2 patients due to grade 3-4 toxicity, 18 patients (17%) suffering hand-foot syndrome, 7 (7%) diarrhea, and 2 (2%) vomiting. Conclusions: This retrospective study demonstrated better efficacy of sorafenib therapy in patients with advanced HCC compared to the literature while progression-free survival and overall survival findings were comparable. The side effect rates indicate that the drug was tolerated well. In conclusion, among the available treatment options, sorafenib is an efficient and tolerable agent in patients with inoperable or metastatic HCC.

Sorafenib Continuation after First Disease Progression Could Reduce Disease Flares and Provide Survival Benefits in Patients with Hepatocellular Carcinoma: a Pilot Retrospective Study

“…And a meta-analysis also showed that sorafenib exerted significant curative effects in hepatocellular carcinoma (Wang et al, 2013). However, variation in the proportion of discontinuation might suggest a disagreement or different estimate of the consequences and risks for sorafenib discontinuation (Berk et al, 2013). A program supported by the China Charity Federation donates sorafenib treatment after administration for 3 months if patients are believed to benefit from continuation, regardless of the presence of PD.…”

Efficacy and Safety of Sorafenib for Advanced Non-Small Cell Lung Cancer: a Meta-analysis of Randomized Controlled Trials

“…Others such as c-Raf, b-Raf, c-Kit and Flt3 are also key members of critical pathways for cell proliferation, differentiation and apoptosis (Kemmer et al, 2004;Kindler et al, 2010;Maurer et al, 2011;Berk et al, 2013). Sorafenib may have anti-tumor activities through a dual mechanism, acting indirectly on the tumor angiogenesis via VEGFR/PDGFR pathways and directly on tumor growth by inhibition Raf/Kit/Flt3 signaling (Wilhelm et al, 2008).…”

Schedule-Dependent Effects of Kappa-Selenocarrageenan in Combination with Epirubicin on Hepatocellular Carcinoma

“…Currently, a variety of cytotoxic and antiproliferative agents have been tested in Hepatocellular carcinoma (HCC) treatment, which are used alone, or in combination with other drugs or other treatment modalities (Zhu, 2006;Boulin et al, 2011;Berk et al, 2013). However, high doses of these drugs lead to severe toxicities, which have a negative effect on patients' survival (Berk et al, 2013).…”

“…However, high doses of these drugs lead to severe toxicities, which have a negative effect on patients' survival (Berk et al, 2013). The use of less toxic doses in combination with other anti-proliferative agents would be desirable (Lee et al, 2004;Abou-Alfa et al, 2010).…”