Sorafenib in treatment of patients with advanced hepatocellular carcinoma: a systematic review.
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.


METHODS
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.
Liver Cancer Institute, Zhongshan Hospital, Fudan University, and Shanghai Key Laboratory for Organ Transplantation, Shanghai 200032, China.
Xin
X
Zhang
Xin-Rong
XR
Yang
Xiao-Wu
XW
Huang
Wei-Min
WM
Wang
Ruo-Yu
RY
Shi
Yang
Y
Xu
Zheng
Z
Wang
Shuang-Jian
SJ
Qiu
Jia
J
Fan
Jian
J
Zhou
D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008875:Middle Aged; D009536:Niacinamide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D000077157:Sorafenib; D000509:alpha-Fetoproteins / Q000032:analysis
D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D000509:alpha-Fetoproteins; D009536:Niacinamide; D000077157:Sorafenib