5-FU cardiotoxicity: current evidence and clinical implications

Fluoropyrimidines, including 5-fluorouracil (5-FU) and its oral prodrug capecitabine, are widely used in the treatment of solid tumors. While generally well tolerated, these agents can cause cardiotoxicity, with reported incidence rates ranging from 0 to 35%. Cardiac manifestations include angina, acute coronary syndromes, hypotension, arrhythmias, myocarditis, and heart failure. The primary mechanism of toxicity is thought to involve coronary vasoconstriction and microvascular dysfunction, though direct myocardial and endothelial damage may also contribute. Risk factors remain poorly defined, and cardiotoxicity can occur even in patients without pre-existing heart disease. Diagnostic tools, including biomarkers such as NT-proBNP and troponin, as well as echocardiography and cardiac MRI, play a critical role in early detection. Management typically involves discontinuation of 5-FU and symptomatic treatment with vasodilators and beta-blockers. Prophylactic strategies remain controversial, and guideline-directed therapy is largely based on case reports and observational data. Rechallenge with 5-FU carries a high risk of recurrence and should be approached with caution. Mult