title: Risk of treatment-related mortality with sorafenib in patients with cancer.
abstract: BACKGROUND
  Fatal adverse events (FAEs) have been reported with sorafenib, a vascular endothelial growth factor receptor kinase inhibitor (VEGFR TKI). We here performed an up-to-date and detailed meta-analysis to determine the overall risk of FAEs associated with sorafenib.
  
  
  METHODS
  Databases, including PubMed, Embase and Web of Science, and abstracts presented at the American Society of Clinical Oncology annual meetings were searched to identify relevant studies. Eligible studies included randomized controlled trials evaluating sorafenib effects in patients with all malignancies. Summary incidence rates, relative risks (RRs), and 95% confidence intervals (CIs) were calculated for FAEs. In addition, subgroup analyses were performed according to tumor type and therapy regimen.
  
  
  RESULTS
  13 trials recruiting 5,546 patients were included in our analysis. The overall incidence of FAEs with sorafenib was 1.99% (95%CI, 0.98-4.02%). Patients treated with sorafenib had a significantly increased risk of FAEs compared with patients treated with control medication, with an RR of 1.77 (95%CI 1.25-2.52, P=0.001). Risk varied with tumour type, but appeared independent of therapy regimen. A significantly increased risk of FAEs was observed in patients with lung cancer (RR 2.26; 95% CI 1.03-4.99; P= 0.043) and renal cancer (RR 1.84; 95% CI 1.15-2.94; P= 0.011). The most common causes of FAEs were hemorrhage (8.6%) and thrombus or embolism (4.9%).
  
  
  CONCLUSIONS
  It is important for health care practitioners to be aware of the risks of FAEs associated with sorafenib, especially in patients with renal and lung cancer.
authors.affiliation: Department of Health Statistics, Second Military Medical University, Shanghai, China E-mail : hejia63@yeah.net.
authors.forename: Xin-Ji
authors.initials: XJ
authors.lastname: Zhang
authors.forename: Tian-Yi
authors.initials: TY
authors.lastname: Zhang
authors.forename: Fei-Fei
authors.initials: FF
authors.lastname: Yu
authors.forename: Xin
authors.initials: X
authors.lastname: Wei
authors.forename: Ye-Sheng
authors.initials: YS
authors.lastname: Li
authors.forename: Feng
authors.initials: F
authors.lastname: Xu
authors.forename: Li-Xin
authors.initials: LX
authors.lastname: Wei
authors.forename: Jia
authors.initials: J
authors.lastname: He
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects*; D002986:Clinical Trials as Topic; D064420:Drug-Related Side Effects and Adverse Reactions / Q000209:etiology / Q000401:mortality*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000401:mortality*; D009536:Niacinamide / Q000009:adverse effects / Q000031:analogs & derivatives*; D010671:Phenylurea Compounds / Q000009:adverse effects*; D011379:Prognosis; D012307:Risk Factors; D000077157:Sorafenib; D015996:Survival Rate
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib