Cardiotoxicity of 5-fluorouracil

Area of Science:

• Cardiology
• Oncology
• Pharmacology

Background:

• 5-fluorouracil (5-FU) is a widely used cytostatic agent with known cardiac side effects.
• The incidence of 5-FU-induced cardiotoxicity ranges from 1.2-7.6%, with severe events being rare (<1%).
• Mechanisms of cardiotoxicity differ from other agents like anthracyclines, with myocardial ischemia suggested.

Purpose of the Study:

• To review the cardiac side effects of 5-fluorouracil (5-FU).
• To explore potential mechanisms of 5-FU cardiotoxicity.
• To discuss management strategies for 5-FU-induced cardiac events.

Main Methods:

• Review of existing literature on 5-FU cardiotoxicity.
• Analysis of proposed mechanisms including endothelial dysfunction and coronary spasm.
• Evaluation of treatment options for cardiac side effects.

Main Results:

• Cardiac events associated with 5-FU include arrhythmias, myocardial infarction, and sudden cardiac death.
• Potential mechanisms involve direct endothelial toxicity, nitric oxide synthase inhibition, protein kinase C activation, and rheological effects.
• Coronary artery disease may increase the risk of cardiac events.

Conclusions:

• 5-FU cardiotoxicity appears distinct from other chemotherapeutics, with ischemia as a potential driver.
• Calcium antagonists (e.g., verapamil) and nitrates may help manage 5-FU-induced coronary spasms.
• Management may involve symptomatic treatment and modification of the 5-FU regimen, with toxicity often being reversible.