5-fluorouracil and cardiotoxicity: a review

Abstract

Fluoropyrimidines such as 5-fluorouracil (5-FU) form the foundation of a wide variety of chemotherapy regimens. 5-FU is in fact the third most commonly used chemotherapeutic agent in the treatment of solid malignancies across the world. As with all chemotherapy, balancing the potential benefits of therapy against the risks of drug-related toxicity is crucial when clinicians and patients make shared decisions about treatment. 5-FU is the second most common chemotherapeutic drug associated with cardiotoxicity after anthracyclines, which can manifest as chest pain, acute coronary syndrome/myocardial infarction or death. Nevertheless a widespread appreciation of 5-FU-related cardiotoxicity and its implications is lacking amongst clinicians. In this review, we outline the incidence, possible risk factors, and likely pathophysiological mechanisms that may account for 5-FU-related cardiotoxicity and also highlight potential management strategies for this poorly understood clinical entity.

5‐Fluorouracil‐induced acute coronary syndrome

“…Unfortunately, 5‐FU is also the second most common chemotherapeutic agent causing cardiotoxicity, with a reported incidence between 2% and 18%. Some of the reported difference in incidence can be accounted for by the differences in treatment duration, dose, additional agents, and patient characteristics . Capecitabine, which is an oral pro‐drug of 5‐FU, has also been associated with cardiotoxicity, with a reported incidence between 3% and 9% .…”

“…Some of the reported difference in incidence can be accounted for by the differences in treatment duration, dose, additional agents, and patient characteristics . Capecitabine, which is an oral pro‐drug of 5‐FU, has also been associated with cardiotoxicity, with a reported incidence between 3% and 9% . While the most common manifestation of 5‐FU‐induced cardiotoxicity is chest pain, presentations can vary from arrhythmias, myocarditis and pericarditis, heart failure and even death .…”

“…Indeed, both experimental and physiological studies have hinted at these being the primary pathways. However, further vigorous prospective investigations in appropriate clinical settings as well as experimental models are required to provide evidence …”

“…While it is universally agreed that the first step should be to cease the infusion immediately and then administer medical anti‐anginal therapy aimed at symptomatic relief with calcium channel blockers (CCBs) and/or nitrates, the challenge of establishing a causal relationship between exposure and symptoms remains daunting. Fortunately, CCBs and nitrates have been shown to abort symptoms in up to 69% of affected patients . However, there remains a distinct lack of a definitive test to establish 5‐FU as the cause.…”

“…However, this is not widely available and its role in this setting has not been validated. Moreover, there is no evidence to establish that positive provocation tests predict cardiotoxicity …”