The Prevalence of 5-Fluorouracil and Capecitabine Cardiotoxicity: A Systematic Review and Meta-Analysis

Abstract

Background: The incidence of cardiotoxicity events in patients who use 5-fluorouracil (5-FU) and capecitabine monotherapy remains unclear since previous studies reported the prevalence in patients who used combination regimens. We aimed to systematically review and meta-analyze the incidence of cardiotoxicity in fluorouracil and capecitabine monotherapy users. Methods: The study protocol was registered with PROSPERO (CRD42023441627). Systematic searches were conducted in five databases (CINAHL, OpenGrey, PubMed, ScienceDirect, and Scopus). The Cochrane Risk-of-Bias tool and the Risk Of Bias In Nonrandomized Studies were used to evaluate the risk of bias. Pooled prevalence and 95% confidence interval (CI) were calculated using the DerSimonian-Laird random effect models. The funnel plot was used to assess the publication bias. Results: Eighty studies were included. There were 24 randomized controlled trials (RCTs) with low to high risk of bias and 56 nonRCTs with critical risk of bias. The pooled prevalence of cardiotoxicity from 5-FU was 3.5% (95% CI: 2.7 - 4.2; P < 0.001; I2 = 73.86%). The pooled prevalence of cardiotoxicity in capecitabine users was 2.8% (95% CI: 1.6 - 4.0; P < 0.001; I2 = 72.62%). Conclusions: The prevalence of cardiotoxicity from 5-FU and capecitabine was classified as common. Cardiotoxicity may have not been associated with the cumulative dose of 5-FU or capecitabine.