br A number of research questions
A number of research questions need to be answered in future studies, including the safety of 5-FU re-challenge after a previous 5-FU-associated cardiac event and the feasibility of using another fluoropyrimidine (eg, capecitabine, S-1, or TAS-01) following a 5-FU-associated cardiac event. Moreover, among patients with recent cardiac events (eg, unstable P 22077 or supraventricular arrhythmia), it is
important to determine if there is a safe “washout period,” following which fluoropyrimidines can be used. It is notable that many clinical trials used 1 year as the potential “washout period” between cardiac events and the use of 5-FU. However, this seems more to be an empirical estimate, and more formal assessment of this topic is needed.
In conclusion, bevacizumab- and panitumumab-containing reg-imens 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. Practicing oncologists should pay a specific attention to cardiac toxicities among patients treated with any of these regimens.
Clinical Practice Points
This pooled analysis includes de-identified patient-level datasets from 5 randomized studies (NCT00272051, NCT00305188, NCT00115765, NCT00364013, and NCT00384176). 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.
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 pre-dicting cardiac toxicities, only bevacizumab-containing regimens (P ¼ .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 regi-mens were predictive of the occurrence of arrhythmias (P < .001).
Likewise, within multivariate logistic regression analysis for fac-tors predicting cardiac ischemia, only bevacizumab-containing regimens were predictive of ischemic events (P ¼ .004).
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The authors have stated that leukocytes have no conflicts of interest.
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