1 title 1 subtitle 2 chemotherapy induced cardiac toxicity russell huntsinger, md cardiologist
TRANSCRIPT
1
Title 1Subtitle 2
Chemotherapy Induced Cardiac Toxicity
Russell Huntsinger, MDCardiologist
2
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.
3
Chemotherapy Agents that Cause Cardiac Toxicity
• Doxorubicin (Adriamycin)
• Epirubicin
• Idarubicin
• Cyclophosphamide
• Fluorouracil
• Mitoxantrone
4
Anthracyclines
• Are the most common cause of cardiac toxicity in cancer patients.
5
Anthracyclines
• Used to treat a wide range of hematological and solid malignancies.
6
Chemotherapy drugs that have been reported to cause abnormalities in heart rhythm
• Gemtuzumab ozogamicin
• Paclitaxel
• Idarubicin
• Tyrosine kinase inhibitors
• Monoclonal antibodies
7
Occurrence
• Clinical heart failure generally occurs within a month to a year after anthracycline treatment.
• May occur up to 6 -10 years or later.
8
How is it diagnosed
• Heart sound – stethoscope
• Chest X-ray
• ECG
• Echo
• MUGA scan
9
What are the symptoms?
• Fatigue
• Shortness of breath on exertion
• Discomfort lying in supine
• Swelling of the ankles
10
• Long cardiac toxicity can manifest as ventricular dysfunction and clinical heart failure.
11
Why?
• It is thought that direct myocardial injury is from free radicals.
12
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.
13
• 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
14
Reducing Drug Cardiotoxicity
• Structural modifications to the doxorubicin molecule (epirubicin).
• Incorporation into liposomes (doxorubicin)
• Development of structurally related drugs (mitoxantrone).
15
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.
16
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.
17
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
18
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.
19
Diagnostics
• Performed through echocardiogram.
• Abnormalities in diastolic dysfunction through Doppler.
• Cardiac biomarkers such as troponin or B-type natriuretic peptide (BNP) in monitoring chemotherapy induced cardiotoxicity is still be studied.
20
How is it treated
• Stopping or reducing the dose.
• Diuretics
• Digitalis drugs
• ACE inhibitors
• Beta-Blockers
21
• 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
22
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.