title: Risk of cardiovascular toxicities in patients with solid tumors treated with sunitinib, axitinib, cediranib or regorafenib: an updated systematic review and comparative meta-analysis.
abstract: BACKGROUND
  We performed a systematic review and comparative meta-analysis of cardiovascular toxicities associated with sunitinib, axitinib, cediranib or regorafenib; oral multi tyrosine kinase inhibitors.
  
  
  METHODS
  Eligible studies included randomized phase II and III trials of patients with solid tumors on sunitinib, axitinib, cediranib or regorafenib describing daily events of hypertension, left ventricular dysfunction, bleeding or thrombosis.
  
  
  RESULTS
  Patients treated with these four agents had a significantly increased risk of all-grade hypertension and bleeding. The RR of all-grade hypertension, bleeding, thrombosis and cardiac dysfunction were 2.78 (95% CI 2.03-3.81; p<0.00001), 1.93 (95% CI 1.41-2.64; p<0.00001), 0.85 (95% CI 0.60-1.19; p=0.50), 2.36 (95% CI 0.95-5.87; p=0.06), respectively. Exploratory subgroup analysis showed no effect of the agent used (sunitinib vs. axitinib vs. cediranib) in the risk of hypertension; while for bleeding, only the sunitinib subgroup RR was significant compared to axitinib or cediranib.
  
  
  CONCLUSIONS
  Our meta-analysis has demonstrated that sunitinib, axitinib, cediranib and regorafenib are associated with a higher risk of developing all grade and high grade hypertension compared with control. While for bleeding, only the sunitinib subgroup RR was significant compared to axitinib or cediranib. Clinicians should be aware of these risks and perform regular cardiovascular monitoring.
authors.affiliation: Clinical Oncology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt. Electronic address: omar.abdelrhman@med.asu.edu.eg.
authors.forename: Omar
authors.initials: O
authors.lastname: Abdel-Rahman
authors.affiliation: Medical Microbiology and Immunology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
authors.forename: Mona
authors.initials: M
authors.lastname: Fouad
mesh_terms: D020533:Angiogenesis Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D000077784:Axitinib; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000453:epidemiology* / Q000209:etiology*; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000627:therapeutic use; D015994:Incidence; D007191:Indazoles / Q000009:adverse effects / Q000627:therapeutic use; D007211:Indoles / Q000009:adverse effects / Q000627:therapeutic use; D009369:Neoplasms / Q000150:complications* / Q000188:drug therapy; D010671:Phenylurea Compounds / Q000009:adverse effects / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use; D011758:Pyrroles / Q000009:adverse effects / Q000627:therapeutic use; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use; D012306:Risk; D000077210:Sunitinib
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D007093:Imidazoles; D007191:Indazoles; D007211:Indoles; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D011758:Pyrroles; D011799:Quinazolines; C559147:regorafenib; D000077784:Axitinib; C500926:cediranib; D000077210:Sunitinib
keywords: Cardiovascular toxicities; Hypertension; Left ventricular dysfunction; Meta-analysis; Sunitinib