From the Guidelines
For a patient with a history of cardiac stenting but normal left ventricular ejection fraction (LVEF), you can consider administering doxorubicin as part of the CAP (cyclophosphamide, doxorubicin, cisplatin) chemotherapy regimen, but with caution and close cardiac monitoring. The patient's normal LVEF and history of cardiac stenting require careful consideration of the potential risks and benefits of doxorubicin therapy. According to the 2016 ESC position paper on cancer treatments and cardiovascular toxicity 1, anthracyclines like doxorubicin have a high efficacy for treating solid tumors and hematological malignancies, but may cause irreversible cardiac damage. The incidence of left ventricular dysfunction associated with doxorubicin is dose-dependent, ranging from 3-5% at a cumulative lifetime dose of 400 mg/m² to 18-48% at a dose of 700 mg/m². Given the patient's cardiac history, it is essential to start with a standard dose of doxorubicin if the LVEF is truly normal (typically ≥50-55%) and there are no other cardiac risk factors. However, close cardiac monitoring is crucial, including baseline and regular LVEF assessments during treatment. Consideration of dose reduction (by 25-50%) may be necessary if there are additional cardiac risk factors such as hypertension, diabetes, prior chest radiation, or if the patient is elderly. The cumulative lifetime doxorubicin dose should not exceed 450 mg/m². A cardio-oncology consultation before initiating treatment would be valuable to establish a monitoring plan and determine the optimal doxorubicin dosing strategy for this specific patient with cardiac history. The 2018 ASCO clinical practice guideline focused update on selection of optimal adjuvant chemotherapy and targeted therapy for early breast cancer 2 also supports the use of anthracyclines in patients who can tolerate them, but emphasizes the importance of careful patient selection and monitoring. In summary, doxorubicin can be considered for this patient, but with careful monitoring and consideration of potential cardiac risks.
From the FDA Drug Label
Myocardial toxicity manifested in its most severe form by potentially fatal congestive heart failure (CHF) may occur either during therapy or months to years after termination of therapy The probability of developing impaired myocardial function based on a combined index of signs, symptoms and decline in left ventricular ejection fraction (LVEF) is estimated to be 1 to 2% at a total cumulative dose of 300 mg/m 2 of doxorubicin, 3 to 5% at a dose of 400 mg/m 2, 5 to 8% at 450 mg/m 2 and 6 to 20% at 500 mg/m 2 Risk factors (active or dormant cardiovascular disease, prior or concomitant radiotherapy to the mediastinal/pericardial area, previous therapy with other anthracyclines or anthracenediones, concomitant use of other cardiotoxic drugs) may increase the risk of cardiac toxicity Cardiac toxicity with doxorubicin may occur at lower cumulative doses whether or not cardiac risk factors are present.
The patient has a stented heart, which may be considered a cardiac risk factor. Although the KSIF (Kidney and Systemic Inflammatory Function) is in normal range, the presence of a stent indicates pre-existing cardiovascular disease. Given the potential for cardiac toxicity associated with doxorubicin, it is recommended to exercise caution when administering this drug to patients with pre-existing cardiovascular disease. Dose reduction may be considered to minimize the risk of cardiac toxicity. However, the exact dose reduction is not specified in the provided drug labels. It is essential to closely monitor the patient's cardiac function during therapy with doxorubicin, especially in the presence of pre-existing cardiovascular disease 3.
From the Research
Doxorubicin Administration in Patients with Stented Heart
- The patient's heart condition, having been stentuated, is a crucial factor to consider when administering doxorubicin, a chemotherapeutic agent known to have cardiotoxic effects 4, 5, 6, 7, 8.
- The normal range of KSIF (Kidney Function) is also an important consideration, as doxorubicin is primarily excreted through the kidneys.
Cardiotoxicity Mechanisms
- Doxorubicin-induced cardiotoxicity involves various mechanisms, including inflammation, oxidative stress, apoptosis, mitochondria impairment, and dysregulation of autophagy 4, 5, 6, 7, 8.
- These mechanisms can lead to cardiomyopathy and congestive heart failure, which are associated with mortality and morbidity 5, 6, 7.
Administration Considerations
- There is no clear consensus on the administration of doxorubicin in patients with stented hearts, but it is essential to weigh the benefits of treatment against the potential risks of cardiotoxicity 4, 5, 6, 7, 8.
- Reducing the dose of doxorubicin may be considered to minimize the risk of cardiotoxicity, but this should be done under the guidance of a healthcare professional and with close monitoring of the patient's cardiac function 6, 7.
Potential Interventions
- Various pharmacological interventions have been proposed to prevent or mitigate doxorubicin-induced cardiotoxicity, including antioxidant therapies and novel delivery systems 5, 7, 8.
- However, more research is needed to validate the clinical utility of these approaches and to develop effective strategies for preventing or reversing doxorubicin-induced cardiotoxicity 4, 5, 6, 7, 8.