From the Guidelines
Cardiac evaluation is recommended before initiating cyclophosphamide therapy, particularly for patients receiving high-dose regimens, and should include a baseline electrocardiogram, echocardiography to assess left ventricular function, and measurement of cardiac biomarkers such as troponin and BNP, as suggested by the American Society of Clinical Oncology clinical practice guideline 1.
Recommended Cardiac Evaluation
The evaluation should prioritize the assessment of left ventricular function, as the severity of left ventricular systolic dysfunction is a strong predictor of progression from asymptomatic to symptomatic heart failure 1. Two-dimensional echocardiography, coupled with Doppler flow studies, is the preferred imaging modality for monitoring asymptomatic patients due to its portability, availability, non-invasiveness, and safety 1.
Risk Factors and Monitoring
Patients with pre-existing cardiovascular disease, prior anthracycline exposure, or other cardiac risk factors require more comprehensive assessment and regular monitoring during treatment, with repeat echocardiography every 3-6 months depending on dose intensity and risk factors 1. The choice of modalities for screening and detection of cardiotoxicity should depend on local expertise and availability, with a preference for modalities and tests with the best reproducibility and those that provide additional relevant clinical information 1.
Cardiotoxicity Management
Cyclophosphamide-induced cardiotoxicity typically manifests as acute heart failure, myocarditis, or pericarditis, usually occurring within 1-10 days of administration, particularly with high doses 1. Risk mitigation strategies include maintaining adequate hydration, administering the drug in divided doses rather than single large doses, and considering dexrazoxane for high-risk patients 1. If cardiotoxicity develops, cyclophosphamide should be discontinued and appropriate heart failure management initiated promptly.
Key Considerations
- The pathogenic mechanism of cyclophosphamide cardiotoxicity may involve direct injury to vascular endothelial cells, followed by leakage of toxic metabolites, interstitial hemorrhage, and edema 1.
- The estimated incidence of cyclophosphamide-myocarditis (doses >150 mg/kg) is 5% in children, with the overall incidence of myocardial alterations being lower in children than in adults 1.
- High-quality radiation-free imaging is preferred if available, and the same imaging modality and/or biomarker assay should be used for continued screening throughout the treatment pathway 1.
From the FDA Drug Label
Myocarditis, myopericarditis, pericardial effusion including cardiac tamponade, and congestive heart failure, which may be fatal, have been reported with cyclophosphamide therapy Supraventricular arrhythmias (including atrial fibrillation and flutter) and ventricular arrhythmias (including severe QT prolongation associated with ventricular tachyarrhythmia) have been reported after treatment with regimens that included cyclophosphamide The risk of cardiotoxicity may be increased with high doses of cyclophosphamide, in patients with advanced age, and in patients with previous radiation treatment to the cardiac region and/or previous or concomitant treatment with other cardiotoxic agents. Particular caution is necessary in patients with risk factors for cardiotoxicity and in patients with preexisting cardiac disease. Monitor patients with risk factors for cardiotoxicity and with pre-existing cardiac disease.
The recommended cardiology evaluation for patients receiving Cyclophosphamide is to monitor patients with risk factors for cardiotoxicity and with pre-existing cardiac disease 2.
From the Research
Cardiology Evaluation for Patients Receiving Cyclophosphamide
The recommended cardiology evaluation for patients receiving cyclophosphamide includes:
- Electrocardiogram (ECG) monitoring to detect changes in QRS voltage and ST segment abnormalities 3, 4
- Echocardiography to assess left ventricular systolic and diastolic function, as well as to detect pericardial effusion 3, 4, 5
- Troponin I monitoring to detect myocardial cell damage 4, 6
- Brain natriuretic peptide (BNP) and endothelin 1 (ET-1) monitoring to detect neurohumoral activation of heart failure 6
- Close monitoring of patients for signs of congestive heart failure, such as dyspnea, and pericardial tamponade 3, 5
Risk Factors for Cardiotoxicity
Risk factors for cardiotoxicity associated with cyclophosphamide include:
- High doses of cyclophosphamide (200 mg/kg or more) 7, 5
- Combination with other cardiotoxic agents, such as anthracyclines 3
- Pre-existing cardiac dysfunction 6
- Age, with older patients being at higher risk 6
Monitoring and Management
Patients receiving cyclophosphamide should be closely monitored for signs of cardiotoxicity, and management should include: