Cardiac Effects of Cancer Therapy
Summary of Key Points
Incidence
Cardiomyopathy/Chronic Heart Failure
• Anthracyclines: cardiomyopathy/chronic heart failure occurs in 5% to 20% of patients receiving cumulative doxorubicin (more than 450 mg/m2); the incidence is higher in children
• Other antineoplastics (e.g., mitoxantrone and cyclophosphamide): the incidence of cardiomyopathy/chronic heart failure is less than 2%
• Trastuzumab (not common as a single agent; increased risk with anthracycline)
• Radiation therapy: cardiomyopathy/chronic heart failure is common 5 to 20 years after use of a single anteroposterior port
Diagnosis
• Clinical cardiac symptoms—American Heart Association/American College of Cardiology staging, New York Heart Association classification, and Common Terminology Criteria for Adverse Events for Heart Failure
• Radionuclide scans—serial scans including baseline
• Endomyocardial biopsy—Billingham histopathological grading system
• Echocardiography—pericardial effusion/constriction, left ventricular systolic/diastolic dysfunction
• Cardiac magnetic resonance imaging—left ventricular systolic/diastolic dysfunction, myocardial fibrosis/necrosis detected by late gadolinium enhancement
1. A 56-year-old woman presents with a newly diagnosed metastatic breast cancer. A doxorubicin-based adjuvant chemotherapy is planned. Her baseline echocardiography showed a normal left ventricular ejection fraction. What is the best approach to reduce doxorubicin-induced cardiotoxicity?
A Limit the cumulative dose of doxorubicin to less than 450 mg/m2
2. A 49-year-old woman is evaluated for a newly diagnosed HER-positive breast cancer. Treatment with an anthracycline-based chemotherapy, radiation therapy, and trastuzumab is being planned. Which of following choices carries the most significant risk for the development of trastuzumab-related cardiotoxicity?
A Prior chest radiation therapy
B Concurrent use with anthracycline
3. The following choices are characteristic of chemotherapy-induced cardiotoxicity in childhood cancer survivors EXCEPT:
A Cardiotoxicity occurs at a lower accumulative dose of anthracycline.
B Cardiotoxicity tends to be early onset.
C Dexrazoxane significantly reduces the risk of anthracycline-induced cardiotoxicity.
4. A 44-year-old man presents to your clinic for routine follow-up. He has been taking pazopanib for metastatic renal carcinoma. He reports occasional lightheadedness and palpitations. You ordered an electrocardiogram, and the calculated QTc is 550 ms. Which of the following best describes the appropriate care plan for this patient?
1. Answer: A. All these approaches have been used clinically to reduce the risk of doxorubicin-induced cardiotoxicity. Liposome-encapsulated doxorubicin and pegylated doxorubicin have been shown to be less toxic to the heart. Dexrazoxane is the only agent approved by the U.S. Food and Drug Administration to prevent anthracycline-induced cardiotoxicity in patients with metastatic breast cancer (it is not approved for the adjuvant setting yet) and is recommended to be used when the accumulative dose of doxorubicin exceeds 300 mg/m2. However, the most effective approach is to limit the accumulative dose to less than 450 mg/m2. The risk of developing clinical heart failure increases significantly when the accumulative dose exceeds 450 mg/m2 (as high as 25%). Although not mentioned here as a choice, the best way to decrease cardiac toxicity would be to avoid an anthracycline altogether, because cardiotoxicity can happen at any dose. In the case of breast cancer, one should seriously consider a nonanthracycline regimen such as docetaxel in combination with cyclophosphamide if possible.
2. Answer: B. All the choices increase the risk of trastuzumab-related cardiotoxicity. The risk for developing cardiotoxicity is highest for the concurrent use of anthracycline with trastuzumab, with the incidence rate as high as 27% with clinical and subclinical cardiotoxicity (16% clinical heart failure). This approach should be avoided and a subsequent approach should be used (at least 3 weeks apart from anthracycline-based chemotherapy).
3. Answer: B. Cardiotoxicity tends to be late onset in childhood cancer survivors. In a study of 830 children treated in the Netherlands, the incidence of clinical heart failure was 2.5% over a median follow-up of 8.5 years, rising to 5.5% at 20 years. Cardiotoxicity risk occurs at lower cumulative doses. Dexrazoxane significantly reduces the risk of anthracycline-induced cardiotoxicity, despite some concern that it increases the risk of secondary malignant neoplasms as shown in one study; this outcome was not shown in other trials. Female patients tend to be at a higher risk for the development of cardiotoxicity according to Lipsultz’s studies.
4. Answer: D. A patient with symptomatic QTc prolongation should be hospitalized for monitoring. The palpitation and lightheadedness might represent episodes of ventricular arrhythmia, which can degenerate into lethal torsades de pointes and sudden death. Serum potassium and magnesium levels should be assessed and repeated as needed. Pazopanib should be temporally discontinued until the QTc decreases to below 460 ms, electrolyte abnormalities are corrected, and symptoms resolve.
