From the Guidelines
Doxorubicin (also known as Hydroxydaunorubicin) is the component of R-CHOP chemotherapy that can result in cardiomyopathy. This anthracycline medication works by intercalating DNA and inhibiting topoisomerase II, effectively killing rapidly dividing cancer cells, but it also causes cumulative, dose-dependent cardiac damage 1. The risk of developing cardiomyopathy increases significantly when the cumulative lifetime dose exceeds 400-450 mg/m². The cardiac toxicity occurs through multiple mechanisms, including the generation of reactive oxygen species that damage cardiac myocytes, disruption of mitochondrial function, and interference with calcium handling in cardiac cells 2. This can lead to both acute cardiotoxicity and delayed cardiomyopathy, which may develop months or even years after treatment completion.
Key Mechanisms of Cardiotoxicity
- Generation of reactive oxygen species that damage cardiac myocytes
- Disruption of mitochondrial function
- Interference with calcium handling in cardiac cells Patients receiving R-CHOP should have baseline cardiac function assessment before starting treatment, regular monitoring during therapy, and long-term follow-up. Strategies to reduce cardiac risk include limiting cumulative doxorubicin dose, using dexrazoxane as a cardioprotectant in high-risk patients, or considering liposomal formulations of doxorubicin which have lower cardiac toxicity profiles 1.
Monitoring and Prevention
- Baseline cardiac function assessment before starting treatment
- Regular monitoring during therapy
- Long-term follow-up
- Limiting cumulative doxorubicin dose
- Using dexrazoxane as a cardioprotectant in high-risk patients
- Considering liposomal formulations of doxorubicin with lower cardiac toxicity profiles
From the FDA Drug Label
Cardiotoxicity is a known risk of anthracycline treatment. Anthracycline-induced cardiotoxicity may be manifested by early (or acute) or late (delayed) events. ... Delayed cardiomyopathy is manifested by a reduction in LVEF and/or signs and symptoms of congestive heart failure (CHF) The risk of acute manifestations of doxorubicin cardiotoxicity in pediatric patients may be as much or lower than in adults Patients receiving doxorubicin after stopping treatment with other cardiotoxic agents, especially those with long half-lives such as trastuzumab, may also be at an increased risk of developing cardiotoxicity
The component of the regimen that can result in cardiomyopathy is Doxorubicin (Hydroxydaunorubicin), an anthracycline, due to its known risk of cardiotoxicity 3.
From the Research
Cardiomyopathy Component
The component of Rituximab, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), and Prednisone that can result in cardiomyopathy is:
- Doxorubicin, as it is an anthracycline that has been associated with arrhythmias and cardiomyopathy 4, 5, 6, 7
Evidence of Cardiomyopathy
Studies have shown that:
- The use of doxorubicin in the R-CHOP regimen can lead to left ventricular dysfunction and heart failure 4
- Patients with pre-existing cardiac dysfunction are at higher risk of cardiomyopathy when treated with doxorubicin 5
- Doxorubicin has been shown to cause acute and chronic cardiotoxicity in treated patients, including congenital cardiomyopathy in newborns when administered during pregnancy 6
- The substitution of doxorubicin with non-pegylated liposomal doxorubicin (NPL-doxorubicin) did not reduce cardiotoxicity in one study, although cardiac safety signals were elevated in the R-CHOP arm compared to the R-COMP arm 7
Cardiotoxicity Risk
The risk of cardiomyopathy associated with doxorubicin is significant, with:
- A pooled proportion of 4.62% for heart failure in patients treated with R-CHOP or CHOP 4
- A significant increase in reported heart failure when cardiac function was evaluated post-chemotherapy 4
- A high risk of cardiovascular adverse events, including cardiomyopathy, in patients treated with doxorubicin 8