title: Incidence and risk of significantly raised blood pressure in cancer patients treated with bevacizumab: an updated meta-analysis.
abstract: OBJECTIVE
  Bevacizumab is a humanized monoclonal antibody targeting vascular endothelial growth factor. The aim of this study was to gain a better understanding of the overall incidence and risk of significantly raised blood pressure in cancer patients who receive bevacizumab therapy.
  
  
  METHODS
  We performed a meta-analysis of relevant randomized controlled trials (RCTs) identified in PubMed, Cochrane library, Embase, and American Society of Clinical Oncology conferences. Overall incidence rates, relative risks (RRs), and 95% confidence intervals (CIs) were calculated using a random-effects model. The primary clinical endpoint was significantly raised blood pressure (grade 3 or above).
  
  
  RESULTS
  A total of 12,949 cancer patients with a variety of solid tumors from 19 RCTs were included in our meta-analysis. The overall incidence of significantly raised blood pressure was 8% (95% CI 6-10%) among patients receiving bevacizumab. Bevacizumab treatment was associated with a statistically significant increased risk of developing significantly raised blood pressure (RR 5.38, 95% CI 3.63-7.97). The RRs of significantly raised blood pressure in patients receiving bevacizumab at 5 and 2.5 mg/kg per week were 7.17 (95% CI, 3.91-13.13) and 4.11 (95% CI 2.49-6.78), respectively. Among cancer patients, those with renal cell carcinoma (RR 13.77, 95% CI 2.28-83.15) and breast cancer (RR 18.83, 95% CI 1.23-292.29) who received bevacizumab at 5 mg/kg per week had a higher risk of developing significantly raised blood pressure.
  
  
  CONCLUSIONS
  Among the patients included in the trials analyzed in this meta-analysis, the addition of bevacizumab to cancer therapy treatments significantly increased the risk of significantly raised blood pressure. The risk may be dose-dependent and vary with tumor type.
authors.affiliation: R&D Center of New Drug, School of Pharmacy, Second Military Medical University, 325 Guo He Road, Shanghai 200433, People's Republic of China.
authors.forename: Mao Mao
authors.initials: MM
authors.lastname: An
authors.forename: Zui
authors.initials: Z
authors.lastname: Zou
authors.forename: Hui
authors.initials: H
authors.lastname: Shen
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.forename: Meng Li
authors.initials: ML
authors.lastname: Chen
authors.forename: Yong Bing
authors.initials: YB
authors.lastname: Cao
authors.forename: Yuan Ying
authors.initials: YY
authors.lastname: Jiang
mesh_terms: D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D001342:Autonomic Nervous System Diseases / Q000139:chemically induced / Q000188:drug therapy / Q000453:epidemiology*; D000068258:Bevacizumab; D001943:Breast Neoplasms / Q000139:chemically induced / Q000188:drug therapy; D002292:Carcinoma, Renal Cell / Q000139:chemically induced / Q000188:drug therapy; D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000188:drug therapy / Q000453:epidemiology*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000139:chemically induced* / Q000453:epidemiology / Q000378:metabolism; D015994:Incidence; D015201:Meta-Analysis as Topic; D009369:Neoplasms / Q000139:chemically induced / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D042461:Vascular Endothelial Growth Factor A / Q000627:therapeutic use
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab
references.citation: Control Clin Trials. 1986 Sep;7(3):177-88
references.pmid: 3802833
references.citation: Lancet. 1998 Jan 10;351(9096):123-7
references.pmid: 9439507
references.citation: J Clin Oncol. 2005 May 20;23(15):3502-8
references.pmid: 15908660
references.citation: Semin Oncol. 2002 Dec;29(6 Suppl 16):15-8
references.pmid: 12516034
references.citation: J Clin Oncol. 2007 Oct 20;25(30):4743-50
references.pmid: 17909199
references.citation: J Clin Oncol. 2009 Mar 10;27(8):1227-34
references.pmid: 19188680
references.citation: Cancer Res. 2005 Feb 1;65(3):671-80
references.pmid: 15705858
references.citation: N Engl J Med. 2003 Jul 31;349(5):427-34
references.pmid: 12890841
references.citation: Arch Intern Med. 1996 Mar 25;156(6):661-6
references.pmid: 8629879
references.citation: N Engl J Med. 1971 Nov 18;285(21):1182-6
references.pmid: 4938153
references.citation: J Clin Oncol. 2008 Nov 20;26(33):5422-8
references.pmid: 18936475
references.citation: Int J Technol Assess Health Care. 1996 Spring;12(2):195-208
references.pmid: 8707495
references.citation: J Clin Oncol. 2003 Jan 1;21(1):60-5
references.pmid: 12506171
references.citation: Lancet Oncol. 2008 Feb;9(2):117-23
references.pmid: 18221915
references.citation: J Clin Oncol. 2005 Jun 1;23(16):3697-705
references.pmid: 15738537
references.citation: Acta Oncol. 2009;48(1):9-17
references.pmid: 18752081
references.citation: J Clin Oncol. 2009 May 1;27(13):2231-7
references.pmid: 19307500
references.citation: Lancet. 2007 Dec 22;370(9605):2103-11
references.pmid: 18156031
references.citation: N Engl J Med. 2006 Dec 14;355(24):2542-50
references.pmid: 17167137
references.citation: N Engl J Med. 2004 Jun 3;350(23):2335-42
references.pmid: 15175435
references.citation: J Clin Oncol. 2007 Apr 20;25(12):1539-44
references.pmid: 17442997
references.citation: BMJ. 1994 Nov 19;309(6965):1351-5
references.pmid: 7866085
references.citation: Am J Kidney Dis. 2007 Feb;49(2):186-93
references.pmid: 17261421
references.citation: Control Clin Trials. 1996 Feb;17(1):1-12
references.pmid: 8721797
references.citation: J Clin Oncol. 2004 Jun 1;22(11):2184-91
references.pmid: 15169807
references.citation: J Urol. 2008 Sep;180(3):860-5; discussion 865-6
references.pmid: 18635227
references.citation: N Engl J Med. 2007 Dec 27;357(26):2666-76
references.pmid: 18160686
references.citation: J Clin Oncol. 2005 Feb 1;23(4):792-9
references.pmid: 15681523
references.citation: J Clin Oncol. 2008 Apr 20;26(12):2013-9
references.pmid: 18421054