Abstract
Introduction: Cancer patients are at increased risk of experiencing cardiotoxicity during their fluoropyrimidine-based chemotherapy. However, risk factors for fluoropyrimidine-induced cardiotoxicity (FIC) are not entirely understood. Methods: We searched PubMed, PsycINFO, IPA, CINAHL, Web of Science and ClinicalTrials.gov for studies published between January 1, 1990 and December 31, 2019, examining risk factors for cardiotoxicity induced by 5-fluorouracil, capecitabine or floxuridine. Two reviewers independently assessed publication quality and extracted study-level data into standardized evidence tables. Review Manager 5 software was used to convert data to risk ratios (RRs) and calculate pooled RRs for meta-analyses using a random-effects method. We conducted a Cochran’s Q test and obtained I 2 index to quantify study heterogeneity in each meta-analysis, with prediction interval (PI) to show the expected range of true effects in future similar studies. Results: Of 690 publications identified for abstract and title screening, 22 unique studies were included in the final review, and 20 of them had sufficient data for meta-analyses. Results indicated that patients undergoing capecitabine-based combination therapy had a higher risk of FIC than those with capecitabine monotherapy (pooled RR=1.61, 95% CI=1.01-2.55, I 2 =0%, 95% PI=0.08-31.71). Also, patients with pre-existing cardiac disease (pooled RR=3.01, 95% CI=2.02-4.49, I 2 =42%, 95% PI=1.03-8.78), hypertension (pooled RR=1.52, 95% CI=1.20-1.93, I 2 =0%, 95% PI=1.08-2.13) or smoking habit (pooled RR=2.22, 95% CI=1.03-4.78, I 2 =39%, 95% PI=0.15-32.46) had a significantly higher risk of FIC than their counterparts, while gender and comorbidities including diabetes, hyperlipidemia, and obesity were not significant risk factors of FIC. Conclusions: Cancer patients with pre-existing cardiac disease, hypertension, and smoking behavior had a higher risk of FIC when they are undergoing fluoropyrimidine-based treatments. Further research is needed to develop risk assessment tools for a risk prediction of FIC among cancer patients, which could advance risk stratification strategies and improve patient outcomes during the application of fluoropyrimidine-based treatments.
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