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.

Keywords: 5-fluorouracil; cardiotoxicity; chemotherapy; coronary vasospasm; fluoropyrimidine.

Figure 1.

Diagram outlining the two potential mechanisms by which 5-fluorouracil could lead to cardiotoxicity: direct cellular damage and ischemia. 5-FU, 5-fluorouracil; DPD, dihydropyrimidine dehydrogenase; NO, nitric oxide; RBC, red blood cell; vWF, von Willebrand factor. *Takatsubo cardiomyopathy is typically seen as a structural cardiomyopathic process, though there is some evidence which suggests that ischemia may contribute to the pathophysiology of this process. This remains a controversial area that requires further investigation.

Figure 2.

Flow diagram demonstrating a suggested treatment approach for patients who have experienced suspected cardiotoxicity related to 5-fluorouracil chemotherapy. 5-FU, 5-fluorouracil; CAD, coronary artery disease; CCB, calcium channel blocker. *When significant CAD has not been demonstrated clinicians could consider invasive pharmacologic provocation testing to identify reproducible coronary vasospasm, though this should only be undertaken by experienced operators in appropriately resourced centers.