5-fluorouracil (5-FU) is an antimetabolite that is commonly used for treatment of solid tumors. The most serious side effect is cardiotoxicity that can trigger angina, myocardial infraction, arrhythmias and sudden death.1 The reported incidence of 5-FUinduced cardiotoxicity ranges from 1.27 to 18%.2 Cardiotoxicity can occur at any doses during bolus or continuous infusion.3
A 43-year-old man without any significant cardiac history or risk factors was admitted to the oncology ward with the diagnosis of colon cancer. During his hospital stay, he was treated with a chemotherapy regimen consisting of leucovorin, irinotecan, avastin (betacizumab), and 5-FU. During his 5-FU infusion, he complained of typical angina. His ECG showed new changes consistent with peaked tall T waves (see Figure 1). His cardiac enzymes remained negative. His symptoms and electrocardiogram (ECG) changes resolved after intravenous nitroglycerin infusion. He remained angina free during his hospital stay and was discharged a few days later.
During the next chemotherapy cycle with 5-FU infusion, he had recurrent angina and tall T waves with anterior ST elevation on his ECG. After initial therapy with nitrate and calcium channel blockers, his angina resolved with normalization of his ECG changes. His coronary angiogram revealed normal coronaries (see Figure 2).
Chest pain induced by 5-FU infusion can be confusing. Rarely, coronary events can be induced during 5-FU infusion that can be lethal. The occurrence of cardiac adverse events has been reported to be between 1.2 and 7.6%.4
History of previous cardiac disease increases the probability of 5-FU-induced cardiac events.5 The underlying mechanism for 5-FU-induced coronary spasm is unknown. Direct effect of 5-FU on the myocardial tissue can be related to a reduction in myocardial adenosine triphosphate (ATP) synthesis triggering vasospasm.6
The occurrence of late angina after the completion of 5-FU infusion has been also reported. Late release of endothelin- 1 by 5-FU metabolites has been thought to be a possible mechanism for 5-FU-induced late angina.7 Diagnosis of 5-FU-induced late angina can be difficult to make as it usually occurs after discharge. Cardiotoxicity of 5-FU has been found to be higher with concomitant administration of other chemotropic agents such as leucovorin or irinotecan.8 5-FU-induced electrocardiographic changes are more common in patients with coronary artery disease.9 Thus, the presence of coronary artery disease needs to be ruled out in these patients.
There is no standardized treatment for 5-FU-induced coronary spasm.8 Calcium channel blockers such as verapamil as well as nitrates have been successfully used for prophylaxis before 5-FU infusion in patients with known coronary artery disease10 or in patients with angina occurrence during 5-FU infusion.11 In patients with previous severe reactions to 5-FU infusion, raltitrexed should be considered as a substitute for 5-FU in order to prevent recurrent coronary spasm.12