5-Fluorouracil-related Cardiotoxicity; Findings From Five Randomized Studies of 5-Fluorouracil-based Regimens in Metastatic Colorectal Cancer

Abstract

Background: 5-Fluorouracil (5-FU) represents the backbone of systemic therapy regimens of colorectal cancer. The current study aims at evaluating the patterns and predictors of cardiac adverse events associated with various 5-FU-based systemic therapy regimens among patients with metastatic colorectal cancer.

Materials and methods: This pooled analysis includes de-identified patient-level datasets from 5 randomized studies (NCT00272051, NCT00305188, NCT00115765, NCT00364013, and NCT00384176). In order to evaluate factors predicting the development of all cardiac toxicities, arrhythmias, and ischemic events, univariate logistic regression analysis was conducted. Subsequently, factors with P < .05 in univariate analysis were included in multivariate logistic regression analysis.

Results: A total of 3223 patients were included in the pooled analysis. A total of 255 (7.9%) patients developed some form of a cardiac toxicity, among which 153 (4.7%) patients developed some form of arrhythmia and 62 (1.9%) patients developed an ischemic event. Within multivariate logistic regression analysis for factors predicting cardiac toxicities, only bevacizumab-containing regimens (P = .002) and panitumumab-containing regimens (P < .001) were predictive for the occurrence of cardiac toxicity. Similarly, within multivariate logistic regression analysis for factors predicting cardiac arrhythmias, only panitumumab-based regimens were predictive of the occurrence of arrhythmias (P < .001). Likewise, within multivariate logistic regression analysis for factors predicting cardiac ischemia, only bevacizumab-containing regimens were predictive of ischemic events (P = .004).

Conclusions: Bevacizumab- and panitumumab-containing regimens seem to be associated with a higher risk of cardiac toxicities compared with other 5-FU-based regimens. Bevacizumab-containing regimens seem to increase the risk of 5-FU-related ischemic events, whereas panitumumab-containing regimens seem to increase the risk of arrhythmias.

Keywords: 5FU; Arrhythmias; Colon cancer; Ischemia; Rectal cancer.