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BackgroundCardiotoxicity is a serious side effect to treatment with 5-fluorouracil (5-FU), but the underlying mechanisms are not fully understood. The objective of this systematic review was to evaluate the pathophysiology of 5-FU- induced cardiotoxicity.MethodsWe systematically searched PubMed for articles in English using the search terms: 5-FU OR 5-fluorouracil OR capecitabine AND cardiotoxicity. Papers evaluating the pathophysiology of this cardiotoxicity were included.ResultsWe identified 27 articles of 26 studies concerning the pathophysiology of 5-FU-induced cardiotoxicity. The studies demonstrated 5-FU-induced: hemorrhagic infarction, interstitial fibrosis and inflammatory reaction in the myocardium; damage of the arterial endothelium followed by platelet aggregation; increased myocardial energy metabolism and depletion of high energy phosphate compounds; increased superoxide anion levels and a reduced antioxidant capacity; vasoconstriction of arteries; changes in red blood cell (RBC) structure, function and metabolism; alterations in plasma levels of substances involved in coagulation and fibrinolysis and increased endothelin-1 levels and N-terminal-pro brain natriuretic peptide levels. Based on these findings the proposed mechanisms are: endothelial injury followed by thrombosis, increased metabolism leading to energy depletion and ischemia, oxidative stress causing cellular damage, coronary artery spasm leading to myocardial ischemia and diminished ability of RBCs to transfer oxygen resulting in myocardial ischemia.ConclusionsThere is no evidence for a single mechanism responsible for 5-FU-induced cardiotoxicity, and the underlying mechanisms might be multifactorial. Further research is needed to elucidate the pathogenesis of this side effect.

Radiation‐induced cardiovascular disease is well described as a late effect in cancer patients treated with radiation therapy. Advancements in surgery, radiotherapy, and chemotherapy have led to an increasing number of cancer survivors with resultant long‐term side effects related to their cancer treatments. In this review, we describe the short‐ and long‐term cardiovascular consequences of mediastinal radiotherapy and discuss the optimal cardiovascular assessments and diagnostic tools in asymptomatic and symptomatic patients.

Background: Fluoropyrimidines are mainstay chemotherapeutics in the treatment of gastrointestinal cancers and are also used to treat breast cancer and head and neck cancers. However, 5-flourouracil (5-FU) and capecitabine may induce cardiotoxicity that mostly presents as acute coronary syndromes. We compared the incidence of cardiotoxicity induced by 5-FU and capecitabine in patients with colorectal cancer and sought to identify risk markers for cardiotoxicity. Methods: We reviewed all consecutive patients with colorectal cancer who received 5-FU or capecitabine at one institution in the neoadjuvant (2007-2016), adjuvant (2000-2016) or metastatic setting (2007)(2008)(2009)(2010)(2011)(2012)(2013)(2014)(2015)(2016). Results: Totally, 995 patients received 5-FU and 1241 received capecitabine. The incidence of cardiotoxicity induced by 5-FU was 5.2% [95% confidence interval (CI): 3.8-6.6%] and 4.1% (95% CI: 3.0-5.2%) induced by capecitabine (p ¼ .21). The most common events were angina without ischemia (5-FU: 1.6%, capecitabine: 1.3%, p ¼ .53), angina with ischemia on ECG (5-FU: 0.9%, capecitabine: 0.8%, p ¼ .53), unspecified chest pain (5-FU: 0.9%, capecitabine: 0.6%, p ¼ .34), ST-elevation myocardial infarction (5-FU: 0.5%; capecitabine: 0.4%, p ¼ .76) and non-ST-elevation myocardial infarction (5-FU: 0.7%, capecitabine: 0.5%, p ¼ .50). Cardiac arrest or sudden death occurred in 0.5 and 0.4%, respectively (p ¼ 1). No risk markers for cardiotoxicity induced by 5-FU were identified. In the capecitabine group, ischemic heart disease was a risk marker (odds ratio: 2.9, 95% CI: 1.2-7.0, p ¼ .016). Conclusions: Five percent of patients treated with 5-FU developed cardiotoxicity and 4% treated with capecitabine. Ischemic heart disease was a risk marker for cardiotoxicity induced by capecitabine.