title: Risk of hypertension with regorafenib in cancer patients: a systematic review and meta-analysis.
abstract: BACKGROUND
  Regorafenib is a novel multikinase inhibitor approved for use in metastatic colorectal cancer (mCRC) and locally advanced gastrointestinal stromal tumors (GISTs). Hypertension is one of the major adverse events of this agent, but to date the incidence and risk of hypertension with regorafenib have not been systematically investigated. We have conducted a systematic review and meta-analysis of published clinical trials to determine its overall incidence and risk.
  
  
  METHODS
  PubMed, Web of Science and abstracts presented at the American Society of Clinical Oncology annual meetings were searched to identify relevant studies published up to September 9, 2013. Eligible studies were prospective phase II or III clinical trials using regorafenib in cancer patients with data on hypertension available. The incidence and relative risk (RR) of hypertension were calculated using a random-effects model.
  
  
  RESULTS
  Data from a total of 1,069 patients (regorafenib n = 750; controls n = 319) from five clinical trials were included for analysis. The overall incidence of all-grade and high-grade hypertension were 44.4 % [95 % confidence interval (CI) 30.8-59.0 %) and 12.5 % (95 % CI 5.2-27.1 %), respectively. The use of regorafenib in cancer patients was associated with a significantly increased risk of all-grade (RR 3.76, 95 % CI 2.35-5.99) and high-grade (RR, 8.39, 95 % CI 3.10-22.71) hypertension. The risk might vary with tumor types (P = 0.000).
  
  
  CONCLUSIONS
  Patients with cancer receiving regorafenib have a significantly higher risk of developing hypertension. Close monitoring and appropriate management of this hypertension are strongly recommended.
authors.affiliation: Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, 305 East Zhongshan Road, Nanjing, Jiangsu Province, 210002, People's Republic of China.
authors.forename: Zexing
authors.initials: Z
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.forename: Weiwei
authors.initials: W
authors.lastname: Nie
authors.forename: Guichun
authors.initials: G
authors.lastname: Huang
authors.forename: Jinhai
authors.initials: J
authors.lastname: Tang
authors.forename: Xiaoxiang
authors.initials: X
authors.lastname: Guan
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects*; D006801:Humans; D006973:Hypertension / Q000139:chemically induced* / Q000453:epidemiology; D015994:Incidence; D009369:Neoplasms / Q000188:drug therapy* / Q000453:epidemiology; D010671:Phenylurea Compounds / Q000009:adverse effects*; D047428:Protein Kinase Inhibitors / Q000009:adverse effects*; D011725:Pyridines / Q000009:adverse effects*; D012306:Risk
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; C559147:regorafenib