Cardiac toxicities of fluoropyrimidine chemotherapy: A literature review and evaluation of current practice at a large U.K. cancer center.

72 Background: Fluoropyrimidine chemotherapy is a mainstay of the adjuvant and palliative management of colorectal cancer. Cardiac toxicities—including angina, myocardial infarction and arrhythmias—are uncommon complications thought to be mediated by coronary vasospasm. Although potentially life-threatening, they remain poorly described and consensus guidelines regarding patient selection are lacking. To assess current understanding of this toxicity, we performed a literature review of the topic. We then evaluated fluoropyrimidine use at a large UK cancer center to investigate current practice. Methods: MEDLINE, EMBASE and the Cochrane central register of controlled trials were searched to March 1 2021 using the search terms (fluorouracil OR capecitabine) AND—separately—cardiotoxicity, heart disease, and rechallenge*. Original research articles in English were included and their findings summarised. The case notes of all patients who underwent surgery for pathological stage III colon cancer between January 1 2017 and December 31 2019 at Leeds Cancer Centre were reviewed. The proportion of patients who experienced cardiac toxicity during adjuvant chemotherapy was assessed. The proportion of patients who were not offered adjuvant chemotherapy due to cardiac risk was identified. Results: The three search strategies identified 582, 55 and 21 citations respectively, of which 28, 7 and 7 full texts were retrieved for further evaluation following review of titles and abstracts. The reported incidence of fluoropyrimidine cardiotoxicity varied widely, as did its definition. Over half of toxicity cases described were ischaemic. Reported risk factors included those for coronary artery disease, although this was not a consistent finding. 125 patients underwent surgery for stage III colon cancer in the study period of whom 81 (65%) received adjuvant chemotherapy. 2 (2.5%) patients failed to complete adjuvant treatment due to cardiac toxicity (angina; cardiac arrest). Pre-existing cardiovascular disease was cited as a reason for not offering adjuvant chemotherapy in 13 of 44 cases (30%). Conclusions: Review of the literature revealed a poor evidence base to guide treatment decisions regarding fluoropyrimidine chemotherapy and cardiac risk. Rates of cardiac toxicity at our center were within expected limits. A number of patients were denied adjuvant chemotherapy due to perceived cardiac risk. A clearer understanding of the pathophysiology and management of fluoropyrimidine cardiotoxicity is urgently required to avoid unnecessarily denying patients effective anti-cancer therapy.