title: Incidence and risk of hypertension with sorafenib in patients with cancer: a systematic review and meta-analysis.
abstract: BACKGROUND
  Sorafenib is used in patients with advanced renal-cell carcinoma (RCC) or hepatocellular cancer, and its application in other types of cancers is also undergoing extensive clinical assessment. Hypertension is one of the major side-effects of this drug, and reported incidences vary substantially between clinical trials. We did a systematic review and meta-analysis of published clinical trials to establish the incidence of hypertension associated with sorafenib. The aim of this study is to gain a better understanding of the overall risk of hypertension in patients with cancer who receive sorafenib.
  
  
  METHODS
  Databases, including Medline (July, 1966, to July, 2007), and Web of Science, and abstracts presented at the American Society of Clinical Oncology annual meetings from 2004 to 2007 were searched to identify relevant studies. Eligible studies were prospective clinical trials of patients with cancer assigned single-drug sorafenib at 400 mg twice daily with data on hypertension available. Incidence and relative risk (RR) of hypertension were calculated using a random-effects or fixed-effects model, depending on the heterogeneity of the included studies.
  
  
  RESULTS
  Nine studies published between January, 2006, and July, 2007, which included a total of 4599 patients with RCC or other solid tumours, were selected from 223 articles screened for analysis. For patients assigned sorafenib, the overall incidence of all-grade and high-grade (ie, grade 3 or 4) hypertension were 23.4% (95% CI 16.0-32.9%) and 5.7% (2.5-12.6%), respectively. No significant difference was noted between patients with RCC or a non-RCC malignancy (all grade: RR 1.03 [95% CI 0.73-1.45], p=0.89; high-grade: RR 1.23 [0.76-1.99], p=0.40) who were assigned sorafenib. Sorafenib was associated with a significantly increased risk of all-grade hypertension in patients with cancer with an RR of 6.11 (2.44-15.32], p<0.001) compared with controls.
  
  
  CONCLUSIONS
  Patients with cancer assigned sorafenib have a significant risk of developing hypertension. Appropriate monitoring and treatment is strongly recommended to prevent cardiovascular complications.
authors.affiliation: Division of Medical Oncology, Department of Medicine, State University of New York, Stony Brook, NY 11794-9447, USA. shenhong.wu@stonybrook.edu
authors.forename: Shenhong
authors.initials: S
authors.lastname: Wu
authors.forename: John J
authors.initials: JJ
authors.lastname: Chen
authors.forename: Andrzej
authors.initials: A
authors.lastname: Kudelka
authors.forename: Janice
authors.initials: J
authors.lastname: Lu
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Zhu
mesh_terms: D020533:Angiogenesis Inhibitors / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001557:Benzenesulfonates / Q000009:adverse effects*; D006801:Humans; D006973:Hypertension / Q000139:chemically induced; D015994:Incidence; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011725:Pyridines / Q000009:adverse effects*; D012306:Risk; D000077157:Sorafenib
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib