title: Incidence and risk of hypertension with a novel multi-targeted kinase inhibitor axitinib in cancer patients: a systematic review and meta-analysis.
abstract: OBJECTIVE
  To investigate the overall incidence and risk of hypertension in cancer patients who receive axitinib and compare the differences in incidences between axitinib and the other four approved vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs).
  
  
  METHODS
  Several databases were searched, including Pubmed, Embase and Cochrane databases. Eligible studies were phase II and III prospective clinical trials of patients with cancer assigned axitinib at a starting dose of 5 mg orally twice daily with data on hypertension available. Overall incidence rates, relative risk (RR), and 95% confidence intervals (CI) were calculated employing fixed or random effects models depending on the heterogeneity of the included trials.
  
  
  RESULTS
  A total of 1908 patients from 10 clinical trials were included. The overall incidences of all grade and high grade hypertension in cancer patients were 40.1% (95% CI 30.9, 50.2%) and 13.1% (95% CI 6.7, 24%). The use of axitinib was associated with significantly increased risk of all grade (RR 3.00, 95% CI 1.29, 6.97, P = 0.011) and high grade hypertension (RR 1.71, 95% CI 1.21, 2.43, P = 0.003). The risk of axitinib associated all grade and high grade hypertension in renal cell carcinoma (RCC) was significantly higher than that in non-RCC. Additionally, the risk of hypertension with axitinib was substantially higher than other approved VEGFR-TKIs, while the risk of all grade hypertension with axitinib was similar to pazopanib (RR 1.05; 95% CI 0.95-, 1.17, P = 0.34).
  
  
  CONCLUSIONS
  While sharing a similar spectrum of target receptors with other VEGFR-TKIs, axitinib is associated with an unexpectedly high risk of developing hypertension. Close monitoring and appropriate management for hypertension are recommended during the treatment.
authors.affiliation: Department of Oncology, The Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai, 200233, China.
authors.forename: Wei-Xiang
authors.initials: WX
authors.lastname: Qi
authors.forename: Ai-Na
authors.initials: AN
authors.lastname: He
authors.forename: Zan
authors.initials: Z
authors.lastname: Shen
authors.forename: Yang
authors.initials: Y
authors.lastname: Yao
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D000077784:Axitinib; D002986:Clinical Trials as Topic; D006801:Humans; D006973:Hypertension / Q000139:chemically induced* / Q000453:epidemiology; D007093:Imidazoles / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D015994:Incidence; D007191:Indazoles / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors*; D012306:Risk
chemical_list: D000970:Antineoplastic Agents; D007093:Imidazoles; D007191:Indazoles; D047428:Protein Kinase Inhibitors; D000077784:Axitinib; D040262:Receptors, Vascular Endothelial Growth Factor
keywords: axitinib; hypertension; meta-analysis; tyrosine kinase inhibitor