Cardiotoxicity with 5‐fluorouracil and capecitabine: more than just vasospastic angina

Abstract

In this case series we present a variety of different cardiac toxicities with 5-fluorouracil and its pro-drug capecitabine, including myocardial infarction, cardiomyopathy, sinoatrial and atrioventricular node dysfunction, takotsubo cardiomyopathy and QT prolongation with torsade-de pointes ventricular tachycardia. We stress the fact that while vasospasm is a well-recognized side-effect of this class of chemotherapeutic agent, broader cardiotoxicity is commonly seen and an increased awareness of the range of toxicity is necessary if repeat toxicity is to be avoided.

Myocardial Protection During Cardiotoxic Chemotherapy

“…5-Fluorouracil and its prodrug capecitabine can cause vasospasm-induced chest pain, 19,20 with a rarer incidence for paclitaxel, tamoxifen, and first-generation TKIs. 11 The risk of cardiovascular ischemic events for some second-generation TKIs is alarmingly high.…”

5-fluorouracil induced cardiotoxicity: Review of the literature

“…Significant prolongation of QTc intervals and frequent ventricular arrhythmias have also been found on Holter monitoring associated with 5-FU infusion [37]. A review of 22 patients demonstrated significant early prolongations of the QT interval which persisted throughout the duration of chemotherapy [40] and another case series described QT prolongation with torsade de pointes in a patient receiving 5-FU infusions [5].…”

“…Acute coronary syndrome (ACS) precipitated by the administration of 5-FU is a rare but well-established phenomenon [1,2] and only one of several adverse cardiac effects related to this chemotherapeutic agent. Additional cardiotoxic effects include cardiomyopathy, vasospastic angina, coronary thrombosis and dissection, malignant arrhythmias, and sudden cardiac death [3][4][5][6][7]. Furthermore, following any cardiac complication, it is essential to weigh the risks of repeat drug administration against the potential for cure of the malignancy given this agent's proven efficacy.…”

“…The wide range of cardiotoxicities related to 5-FU occur less frequently but are typically more serious and include ventricular arrhythmias, cardiomyopathy with significant left ventricular systolic dysfunction, arterial vasospasm, and direct endothelial toxicity, often culminating in myocardial infarction (MI), heart failure (HF), and cardiogenic shock [3][4][5][6][7] (Table 2). 5-FU cardiotoxicity is, in fact, the second most common cause of chemotherapy induced cardiotoxicity, second only to anthracycline cardiotoxicity [10,11].…”

Tissue Doppler echocardiography detects subclinical left ventricular dysfunction in patients undergoing chemotherapy for colon cancer: insights from ONCOECHO multicentre study

“…The cardiotoxic effects of these drugs seem to be multifactorial [16]. The suggested phenomenon of vasospasm induced by 5-FU or capecitabine cannot explain the possibility of cardiomyopathy, sinoatrial and atrioventricular node dysfunction, takotsubo cardiomyopathy, and QT prolongation with torsade de pointes ventricular tachycardia [17]. Although a recent European Society of Cardiology statement on cardiovascular toxicity of cancer treatment emphasises the ischaemic effect of 5-FU [18], cardiotoxicity of pyrimidines seems to have numerous mechanisms, including apoptosis of myocardium, depletion of high-energy phosphate compounds, increased oxygen consumption, impaired antioxidant defence system, and more [16].…”