Cardiovascular Toxicity of Fluoropyrimidines: What We Know

Fluoropyrimidines, including 5-fluorouracil and capecitabine, are widely used in the treatment of numerous malignant neoplasms. However, they are a common cause of chemotherapy-induced cardiac toxicity. The cardiovascular adverse events can range from arrhythmias to myocardial infarction and cardiogenic shock, with incidence rates varying between 1.2% and 30%. Despite increasing recognition of risk factors and clinical presentations, the exact mechanisms underlying fluoropyrimidine cardiotoxicity remain unclear. Proposed mechanisms include coronary vasospasm, direct myocardial toxicity due to mitochondrial injury, endothelial dysfunction, and ferroptosis. It is challenging to identify and diagnose the adverse event because of the variability in clinical manifestations and the absence of specific biomarkers. Biomarkers such as troponins or imaging modalities including electrocardiographic changes and echocardiographic assessment may aid in detecting toxicity, but their predictive value remains limited. The primary approach to management involves discontinuation of therapy and symptomatic treatment. Calcium channel blockers and nitrates are commonly used for vasospasm-related events. Rechallenge strategies incorporating dose modifications and cardioprotective medications have been explored but remain controversial owing to high recurrence rates. This review provides an updated overview of fluoropyrimidine-associated cardiotoxicity, emphasizing epidemiology, pathophysiology, diagnostic approaches, and management strategies to enhance patient safety and treatment outcomes.