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Parameter Clinical Syndromes of Cardiotoxicity Frequency Comments Left Ventricular Dysfunction–Heart Failure Anthracyclines Doxorubicin (and others) +++ Highly dose-dependent; risk factors include age (old and young), prior mediastinal XRT, history of heart disease, decreased ejection fraction (EF), drop in EF on drug therapy, female gender (for children), and other agents (especially trastuzumab); risk decreased by liposomal encapsulation or dexrazoxane. Mitoxantrone ++ Derivative with somewhat lower risk; efficacy questionable; used in patients with multiple sclerosis at lower doses Cyclophosphamide, ifosfamide + Primarily seen with high dose “conditioning” regimens; risk factors are prior mediastinal XRT or anthracycline drug therapy, and imatinib or pentostatin (?); also can have myocarditis, pericarditis, myocardial necrosis Mitomycin + Risk increased with high doses, anthracyclines, or XRT ++ Seen with concurrent anthracycline therapy; caused by retarded metabolism of anthracycline' largely preventable with dosing regimen; not seen with docetaxel; trastuzumab increases risk of heart failure (HF) Trastuzumab ++ Relatively uncommon as single agent; increased risk with anthracyclines, paclitaxel, cyclophosphamide Imatinib, dasatinib ++ Frequency not clear but probably <5%; can be severe; can also cause severe fluid retention with peripheral edema, pleural and pericardial effusion not secondary to left ventricular (LV) dysfunction Sunitinib +++ LV dysfunction common Bevacizumab ++ HF can be seen in setting of severe hypertension, which occurs in 10-25% of patients, depending on dose; anthracyclines may increase HF risk ATRA ++ With retinoic acid syndrome (see text) 5-Fluorouracil (5-FU), capecitabine ++ Acute coronary syndromes (ACS); patients with CAD at increased risk; recurs with rechallenge; vasospasm likely mechanism Cisplatin, carboplatin ++ ACS caused by vasospasm and/or vascular injury; hypertension common Interferon-α + Risk of ischemia increased in patients with CAD; Alkylating agents Taxanes Paclitaxel Targeted therapeutics Ischemic Syndromes Parameter Frequency Comments hypertension common Bevacizumab ++ Arterial thrombotic events in 8.5% of patients >65 yr Vinca alkaloids + ∼1% risk of cardiac events; ischemia possibly caused by coronary spasm Sorafenib ++ 2.5% risk of ACS in preapproval trials Hypertension Cisplatin ++++ Bevacizumab ++++ Sunitinib ++++ Hypotension Rituximab ++ Infusion reactions Alemtuzumab +++ Infusion reactions Interleukin (IL)-2, denileukin ++++ Capillary leak syndrome Interferon-α +++ Within first few hours after treatment ATRA ++ In setting of retinoic acid syndrome Paclitaxel + Bradyarrhythmias; ventricular tachycardia rare Thalidomide ++ Bradyarrhythmias Arsenic trioxide ++++ Prolonged QT; rarely, torsades de pointes Rituximab ++ Occur during or shortly after infusion Arrhythmias