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  • br A number of research questions

    2019-09-20


    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 P 22077 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).
    Acknowledgment
    This publication is based on research using information obtained from www.projectdatasphere.org, which is maintained by Project Data Sphere, LLC. Neither Project Data Sphere, LLC nor the
    owner(s) of any information from the website have contributed to, approved of, or are in any way responsible for the contents of this publication.
    Disclosure
    The authors have stated that leukocytes have no conflicts of interest.
    References
    1. Leung U, Gönen M, Allen PJ, et al. Colorectal cancer liver metastases and con-current extrahepatic disease treated with resection. Ann Surg 2017; 265:158-65. 2. Alter P, Herzum M, Soufi M, Schaefer JR, Maisch B. Cardiotoxicity of 5-fluorouracil. Cardiovasc Hematol Agents Med Chem 2006; 4:1-5.
    4. Depetris I, Marino D, Bonzano A, et al. Fluoropyrimidine-induced cardiotoxicity.
    5. Van Cutsem E, Hoff PM, Blum JL, Abt M, Osterwalder B. Incidence of car-diotoxicity with the oral fluoropyrimidine capecitabine is typical of that reported with 5-fluorouracil. Ann Oncol 2002; 13:484-5.
    7. Project Data Sphere, Available at: https://www.projectdatasphere.org/