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PLoS One. 2015 Mar 27;10(3):e0122735. doi: 10.1371/journal.pone.0122735. eCollection 2015.

Cardiovascular toxicity of multi-tyrosine kinase inhibitors in advanced solid tumors: a population-based observational study.

Author information

  • 1Division 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.
  • 2Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre and Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
  • 3Medical Oncology Department and Translational Research Unit, Albacete University Hospital, Edificio de Investigación, Calle Francisco Javier de Moya, Albacete, Spain.
  • 4Department of Medical Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia.

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.

PMID:
25815472
PMCID:
PMC4376902
DOI:
10.1371/journal.pone.0122735
[PubMed - indexed for MEDLINE]
Free PMC Article
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