title: Cardiovascular toxicity of multi-tyrosine kinase inhibitors in advanced solid tumors: a population-based observational study.
abstract: BACKGROUND
  Treatment with small molecule tyrosine kinase inhibitors (TKIs) has improved survival in many cancers, yet has been associated with an increased risk of adverse events. Warnings of cardiovascular events are common in drug labels of many TKIs. Despite these warnings, cardiovascular toxicity of patients treated with TKIs remains unclear. Here, we evaluate the cardiovascular outcomes of advanced cancer patients treated with small molecule tyrosine kinase inhibitors.
  
  
  METHODS
  A population based cohort study was undertaken involving adults aged >18 years in Ontario, Canada, diagnosed with any advanced malignancy between 2006 and 2012. Data were extracted from linked administrative governmental databases. Adults with advanced cancer receiving TKIs were identified and followed throughout the time period. The main outcomes of interest were rates of hospitalization for ischemic heart disease (acute myocardial infarction and angina) or cerebrovascular accidents and death.
  
  
  RESULTS
  1642 patients with a mean age of 62.5 years were studied; 1046 were treated with erlotinib, 166 with sorafenib and 430 with sunitinib. Over the 380 day median follow-up period (range 6-1970 days), 1.1% of all patients had ischemic heart events, 0.7% had cerebrovascular accidents and 72.1% died. Rates of cardiovascular events were similar to age and gender-matched individuals without cancer. In a subgroup analysis of treatment patients with a prior history of ischemic heart disease, 3.3% had ischemic heart events while 1.2% had cerebrovascular accidents.
  
  
  CONCLUSIONS
  TKIs do not appear to increase the cause-specific hazard of ischemic heart disease and cerebrovascular accidents compared to age and gender-matched individuals without advanced cancer.
authors: Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre and Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada.
authors: Amirrtha
authors: A
authors: Srikanthan
authors: Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre and Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors: Josee-Lyne
authors: JL
authors: Ethier
authors: Medical Oncology Department and Translational Research Unit, Albacete University Hospital, Edificio de Investigación, Calle Francisco Javier de Moya, Albacete, Spain.
authors: Alberto
authors: A
authors: Ocana
authors: Department of Medical Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia.
authors: Bostjan
authors: B
authors: Seruga
authors: Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre and Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors: Monika K
authors: MK
authors: Krzyzanowska
authors: Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre and Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada.
authors: Eitan
authors: E
authors: Amir
mesh_terms: D000328:Adult; D000369:Aged, 80 and over; D002170:Canada; D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000453:epidemiology* / Q000473:pathology; D005260:Female; D006801:Humans; D007211:Indoles / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000139:chemically induced / Q000453:epidemiology* / Q000473:pathology; D009369:Neoplasms / Q000188:drug therapy / Q000453:epidemiology*; D009536:Niacinamide / Q000031:analogs & derivatives / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D011758:Pyrroles / Q000627:therapeutic use; D012307:Risk Factors; D000077157:Sorafenib; D000077210:Sunitinib
chemical_list: D007211:Indoles; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; D009536:Niacinamide; D000077157:Sorafenib; D000077210:Sunitinib