Download Clinical Syndromes of Cardiotoxicity

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