Risk Factors of Fluoropyrimidine Induced Cardiotoxicity Among Cancer Patients: A Systematic Review and Meta-analysis

Cancer patients experienced an increased risk of cardiotoxicity during fluoropyrimidine-based chemotherapy (5-fluorouracil or capecitabine). We searched PubMed, PsycINFO, IPA, CINAHL, Web of Science, and ClinicalTrials.gov for studies published between January 1, 1990 and December 31, 2019, in English, examining risk factors for cardiotoxicity induced by fluoropyrimidine. Included study-level data were converted to risk ratios (RRs) and pooled RRs were calculated for meta-analyses using a random-effects method. Among 690 publications identified for abstract and title screening, 22 unique studies were included in the review, and 20 had sufficient data for meta-analyses. Results indicated that patients undergoing capecitabine-based combination therapy had a higher risk than those with monotherapy (pooled RR = 1.61). Patients with pre-existing cardiac disease (pooled RR = 3.26), hypertension (pooled RR = 1.52) or smoking (pooled RR = 2.22) also had higher risks than their counterparts. Developing risk assessment tools to mitigate the risk could be a viable strategy to improve outcomes for cancer patients undergoing fluoropyrimidine-based treatments.