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Chemotherapy Induced
Cardiac
Toxicity
Title
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Subtitle 2
Russell Huntsinger, MD
Cardiologist
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What is Cardiac Toxicity?
• Damage to the heart muscle by a toxin is
called cardiac toxicity.
• They may cause arrhythmias
• May lead to heart failure
– Does not mean that that the heart has
stopped or is about to stop
– The heart muscle cannot pump with enough
force to supply the body with blood containing
essential oxygen and nutrients.
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Chemotherapy Agents that Cause
Cardiac Toxicity
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Doxorubicin (Adriamycin)
Epirubicin
Idarubicin
Cyclophosphamide
Fluorouracil
Mitoxantrone
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Anthracyclines
• Are the most common cause of cardiac
toxicity in cancer patients.
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Anthracyclines
• Used to treat a wide range of
hematological and solid malignancies.
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Chemotherapy drugs that have been
reported to cause abnormalities in
heart rhythm
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Gemtuzumab ozogamicin
Paclitaxel
Idarubicin
Tyrosine kinase inhibitors
Monoclonal antibodies
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Occurrence
• Clinical heart failure generally occurs
within a month to a year after
anthracycline treatment.
• May occur up to 6 -10 years or later.
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How is it diagnosed
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Heart sound – stethoscope
Chest X-ray
ECG
Echo
MUGA scan
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What are the symptoms?
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Fatigue
Shortness of breath on exertion
Discomfort lying in supine
Swelling of the ankles
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• Long cardiac toxicity can manifest as
ventricular dysfunction and clinical heart
failure.
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Why?
• It is thought that direct myocardial injury is
from free radicals.
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How Can Cardiac Toxicity be
Prevented
• Altering the amount of dose
– Limit anthracyclines
For example:
• if doxorubicin is less than 550mg/m2, there is
a less than 1% chance of cardiac toxicity.
• If doxorubicin is between 560-1155 mg/m2,
the risk increases to 30%
Cur Med Chem. 2001;13:1649-1660.
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• Reported incidence of heart failure in
adjuvant anthracycline therapy trials is 2%
or less.
• Recent studies have reported 10-50%
occurrence of subclinical decline in left
ventricular function > 10% points after
anthracycline treatment.
J Am Coll Cardiol 2007; 50:1435
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Reducing Drug Cardiotoxicity
• Structural modifications to the doxorubicin
molecule (epirubicin).
• Incorporation into liposomes (doxorubicin)
• Development of structurally related drugs
(mitoxantrone).
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Method of Administration
• Evidence that the method of drug administration
may affect the risk of cardiac toxicity.
• Rapid administration of drugs results in high
blood levels, which may cause more heart
damage than the same amount of drug given
over a longer period of time.
• Small doses of drug, more frequently can
decrease the toxicity compared to large doses of
drugs at longer intervals.
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Advancements in chemotherapy
administration
• Liposomal anthracyclines are anthracycline
encapsulated in a liposome.
• By enclosing in lipose, it stays in body longer
due to the immune system doesn’t target it for
elimination and the liver doesn’t break it down
as quickly.
• Current studies indicate that the risk for heart
problems is considerable lower with liposomal
doxorubicin formulations than with conventional
doxorubicin.
Oncologist. 2003;8 Suppl 2:17-24.
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Types of liposomal anthracyclines
• Liposomal daunorubicin (DaunoXome)
• Pegylated liposomal doxorubicin (Doxil)
– Has been studied most extensively and has
demonstrated the most significant reductions
in heart problems
– Has shown a similar anticancer effect to
doxorubicin, but with less cardiac toxicity
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Dexrazoxane (Zinecard)
• Has been shown to prevent or reduce the
severity of heart damage caused by
doxorubicin.
• Thought to protect the heart muscle by
blocking the formation of oxygen free
radicals.
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Diagnostics
• Performed through echocardiogram.
• Abnormalities in diastolic dysfunction
through Doppler.
• Cardiac biomarkers such as troponin or Btype natriuretic peptide (BNP) in
monitoring chemotherapy induced
cardiotoxicity is still be studied.
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How is it treated
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Stopping or reducing the dose.
Diuretics
Digitalis drugs
ACE inhibitors
Beta-Blockers
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• Endomyocardial biopsy may be useful to
help diagnosis anthracycline induced
cardiotoxicity.
• Histological scaling has correlated with left
ventricular function on radionuclide
ventriculogram.
• Has limitations with availability of
technique and high likelihood of missing
the involved areas via biopsy.
Dis Manage 2008; 11: 1-6
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Survivorship and Cardiac Function
• As effectiveness of cancer treatment
continues to improve, the population of
long term survivors of childhood cancer
will grow – an increase of late onset of
cardiomyopathy will occur.
• Prognosis after heart failure is generally
poor compared to that associated with
idiopathic or ischemic cardiomyopathy.
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