Table 1.
Agent | Toxicity | Proposed Mechanisms | Age-Related Toxicity |
---|---|---|---|
Anthracyclines | Left ventricular dysfunction CHF Pericarditis and/or myocarditis |
Generation of reactive free radicals Induction of apoptosis Changes in ATP production Mitochondrial DNA damage Downregulation of mRNA expression for sarcoplasmic reticulum calcium ATPase |
Increased risk at age > 65 years Risk increases as cumulative dose increases |
Fluorouracil and/or capecitabine | Angina Myocardial infarction Arrhythmia CHF Cardiogenic shock Sudden death |
Vasospasm Direct myocardial toxicity Coronary artery thrombosis Development of arteritis Induction of apoptosis |
Unknown |
Bortezomib | Left ventricular dysfunction CHF |
Induction of endoplasmic reticulum stress after proteasome inhibition | Unknown |
Cyclophosphamide | CHF | Direct endothelial injury Intracapillary microemboli Coronary vasospasm |
Unknown |
Docetaxel and/or paclitaxel | CHF Myocardial ischemia Bradycardia |
Cremophor EL vehicle induction of histamine release Effects on Purkinje system and/or extracardiac autonomic control |
Unknown |
Cisplatin | Thrombosis | Platelet activation and aggregation Disruption of endothelial integrity Elevated von Willebrand factor leading to vasospasm |
Unknown |
Trastuzumab | Left ventricular dysfunction CHF |
Inhibition of HER2 ATP depletion Disruption of mitochondrial integrity |
Increased risk at age > 80 years |
Bevacizumab | CHF Arterial thrombosis Angina Myocardial infarction Hypertension |
Inhibition of VEGF Reduction in nitric oxide and prostacyclin Reduction of myocardial capillary density Cardiac fibrosis |
Inconclusive |
Lapatinib | Left ventricular dysfunction CHF QT prolongation |
Inhibition of HER2 ATP depletion Disruption of mitochondrial integrity |
Unknown |
Imatinib | CHF | Inhibition of c-Abl | Unknown |
Dasatinib | CHF QT prolongation |
Inhibition of c-Abl Inhibition of Src |
Unknown |
Nilotinib | QT prolongation | Unknown | Unknown |
Sunitinib | CHF Hypertension |
Mitochondrial damage Inhibition of tyrosine kinase that regulates hypertensive stress in myocardiocytes Induction of apoptosis ATP depletion Inhibition of VEGF |
Unknown |
Sorafenib | Myocardial ischemia Hypertension |
Inhibition of VEGF Induction of apoptosis |
Unknown |
Erlotinib | Myocardial ischemia Myocardial infarction Thrombosis |
Unknown | Unknown |
Thalidomide and/or lenalidomide | Thrombosis Bradycardia |
Interaction of platelets and endothelium Increased platelet aggregation and von Willebrand factor Activation of vasovagal pathway |
Unknown |
Arsenic trioxide | QT prolongation | Prolongation of action potential | Unknown |
Histone deacetylase inhibitors | Thromboembolism QT prolongation |
Unknown | Unknown |
Radiotherapy | Coronary artery disease Acute pericarditis Myocarditis CHF Valvular disease Conduction disease |
Generation of reactive oxygen species Endothelial damage Development of arteritis Development of cardiac fibrosis |
Unknown |
Abbreviations: ATP, adenosine triphosphate; CHF, congestive heart failure; HER2, human epidermal growth factor receptor 2; mRNA, messenger RNA; VEGF, vascular endothelial growth factor.