title: Risk of treatment-related mortality with sorafenib in cancer patients: a meta-analysis of 20 randomly controlled trials : Risk of sorafenib-associated death.
abstract: BACKGROUND
  Sorafenib is a relatively new multi-kinase inhibitor used to treat a wide range of cancers. As fatal adverse events from sorafenib therapy are rare, their investigation requires a meta-analysis. Aim of the review To provide a meta-analysis of sorafenib-associated fatal adverse events with the most expansive and current data.
  
  
  METHODS
  We searched Medline, EMBASE, Web of Science and Cochrane Library databases. We also searched abstracts from a number of conferences. Twenty trials of sorafenib were found in 9434 cancer patients, tested against placebos and against other drugs. We calculated relative risks and incidences for sorafenib-associated mortality.
  
  
  RESULTS
  Overall incidence of sorafenib-associated mortality was 3.3 %. Patients with renal cell carcinoma (RCC) and thyroid cancer had treatment-related mortality ≥5 %. Patients treated with sorafenib had a significantly greater risk of mortality than those in placebo/control groups, with an RR of 1.75. Subgroup analyses also showed significant differences in sorafenib versus placebo (RR 1.87, 95 % CI 1.23-2.86; I (2) = 0.0 %, P = 0.865); and sorafenib + platinum-based chemotherapy (RR 2.03, 95 % CI 1.15-3.59; I (2) = 0.0 %, P = 0.654). However, sorafenib had lower risk than other multi-targeted antiangiogenic tyrosine kinase inhibitors. Patients with RCC and non-small-cell lung carcinoma were significantly more vulnerable.
  
  
  CONCLUSIONS
  Sorafenib presents a significant risk of fatal adverse events (FAEs) in patients with cancer, especially for RCC or non-small-cell lung carcinoma, and in patients treated with sorafenib + platinum-based chemotherapy. However, compared with other multi-targeted antiangiogenic tyrosine kinase inhibitors, sorafenib has a lower risk of FAEs.
authors.affiliation: Medical College of Nanchang University, No. 461 Bayi Road, Nanchang, China.
authors.forename: Xiongwen
authors.initials: X
authors.lastname: Yang
authors.affiliation: Medical College of Nanchang University, No. 461 Bayi Road, Nanchang, China.
authors.forename: Xiong
authors.initials: X
authors.lastname: Pan
authors.affiliation: The Second Affiliated Hospital of Nanchang University, No. 1 Minde Road, Nanchang, China.
authors.forename: Xiaoshu
authors.initials: X
authors.lastname: Cheng
authors.affiliation: The Second Affiliated Hospital of Nanchang University, No. 1 Minde Road, Nanchang, China. chengyingzhang123@163.com.
authors.forename: Yingzhang
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Thoracic Surgery of Jiangxi Province Tumor Hospital, No. 519 Beijing East Road, Nanchang, China. kuangyukang@aim.com.
authors.forename: Yukang
authors.initials: Y
authors.lastname: Kuang
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000401:mortality*; D009536:Niacinamide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000009:adverse effects* / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D000077157:Sorafenib
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D009536:Niacinamide; D000077157:Sorafenib
keywords: Adverse events; Meta-analysis; Mortality; Relative risk; Sorafenib; Tyrosine kinase inhibitors