BACKGROUND: Sorafenib has become the standard first-line treatment for patients with advanced hepatocellular carcinoma (HCC). This study aimed to assess the efficacy and safety of sorafenib in advanced HCC patients and explore its true value for specific subgroups. DATA SOURCES: A computer-based systematic search from January 2005 to June 2011 with 'sorafenib' and 'advanced hepatocellular carcinoma' as search terms was performed for possible clinical trials. Hazard ratios (HR) and their 95% confidence intervals (CI) for overall survival (OS) and time to progression (TTP), rates of partial response (PR), rates of toxicity effects, and details of subgroup analysis were extracted. Meta-analyses were done using the software Review Manager (version 5.0). RESULTS: Six trials with 1164 patients were included. Based on three randomized controlled trials, the pooled HR (sorafenib/ placebo) was 0.66 for OS (95% CI: 0.56-0.78; P<0.00001) and 0.57 for TTP (95% CI: 0.47-0.68; P<0.00001). The pooled odds ratio (OR) for PR was 2.96 (95% CI: 0.96-9.15; P=0.06). For three single-arm trials, the pooled HR was 0.69 for OS (95% CI: 0.56-0.84; P=0.0002) and 0.64 for TTP (95% CI: 0.52-0.78; P<0.00001). The pooled OR for PR in three single-arm trials was 3.56 (95% CI: 1.22-10.39; P=0.02). Subgroup analysis indicated that sorafenib was less effective in patients with extrahepatic spread (with: P=0.13 vs without: P<0.0001), with normal alpha-fetoprotein level (AFP) (P=0.15 vs elevated: P=0.0006), and with elevated level of serum bilirubin (P=0.06 vs normal: P=0.0009). Sorafenib-based therapy significantly increased the risk of grade 3/4 hand-foot skin reaction, diarrhea, fatigue, and rash/desquamation.CONCLUSIONS: Sorafenib-based therapy benefits advanced HCC patients. Meanwhile, sorafenib is less effective for patients with extrahepatic spread, with normal AFP level and with elevated level of bilirubin.
Xin Zhang, Xin-Rong Yang, Xiao-Wu Huang, Wei-Min Wang, Ruo-Yu Shi, Yang Xu, Zheng Wang, Shuang-Jian Qiu, Jia Fan ,Jian Zhou Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai Key Laboratory for Organ Transplantation, Shanghai 200032, China,Institute of Biomedical Sciences, Fudan University, Shanghai 200032, China
BACKGROUND:The prognostic role of diabetes mellitus (DM) coexisting with hepatocellular carcinoma (HCC) remains controversial.To clarify its impact on survival in HCC patients after curative treatments,a meta-analysis was performed.DATA SOURCES:Eligible studies were identified through multiple search strategies in the databases PubMed (MEDLINE),EMBASE,the Cochrane Library and ACP Journal Club between January 1950 and March 2010.Ten studies fulfilled the inclusion criteria,and data were aggregated comparing overall survival and recurrence-free survival in HCC patients according to DM status.RESULTS:The pooled hazard ratios (HRs) estimate for overall survival was 1.34 (95% CI,1.18-1.51;P<0.0001) and for recurrence-free survival was 1.48 (95% CI,1.00-2.18;P<0.0001),showing a worse survival for HCC with coexisting DM.However,the patients with DM had a shorter survival time in HCV-related HCC (HR=1.71;95% CI,1.10-2.66;P=0.016),while HBV-related cases were not significantly different (HR=1.29;95% CI,0.69-2.40;P=0.182).Meanwhile,the coexistence of DM impaired overall survival in HCC patients with a small tumor burden (HR=1.63;95% CI,1.25-2.12;P<0.0001).CONCLUSION:HCC patients with coexisting DM have a shorter survival time and a higher risk for tumor recurrence after curative treatments,while the precise value should be defined in more clinical trials with consistent methodology,especially prospective studies.
Wei-Min Wang,Yang Xu,Xin-Rong Yang,Yao-Hui Wang,Hai-Xiang Sun and Jia Fan Institute of Biomedical Sciences,Fudan University,Shanghai 200032,China
