Discussion
Acute heart failure due to 5-FU combined with platins with no epicardial coronary artery involvement may compromise patients’ outcomes even in the absence of drug misadministration. Both patients recovered early and presented the same pattern of late gadolinium enhancement on cMR mimicking myocarditis sequela. The adverse drug reaction was dose-independent, most likely due to 5FU. The most likely mechanism is direct cardiomyocyte toxicity given the pathological findings in one of the cases with myocyte necrosis and endothelial lesions or significant cell infiltrates. Cardio-toxicity so far were due to overdoses with high fatality rates. Our brief report highlights the susceptibility of some individuals to present this rare but potentially fatal complication. The complication was unpredictable, one after a single dose in a teenager with no past cardiovascular disease, the other after a re-challenge in an elderly man.
Uridine triacetate may be an alternative for the treatment of 5-FU poisoning if given early (<96 hours).2,4 In our two cases this treatment option was discussed but the drug was not readily available precluding early administration, given the absence of residual measurable 5FU 24 hours after ACU admission.
There is need for increased awareness among pediatricians, oncologists, hematologists, cardiologists, internists, and intensivists since 5FU-related cardiogenic shock may be fulminant with an interest for uridine triacetate supply and mechanical circulatory support as a bridge to full recovery.5
Figure legend. Panel A: Myocardial damage in a right ventricle endomyocardial biopsy from a 15 year-old patient treated with 5-fluorouracil. Focus of myocyte necrosis (arrows) surrounded by mild mononuclear cell infiltration (arrowheads); (H&E stain; Bar = 20 µm). Panel B: Subepicardial late gadolinium enhacement (arrow) in the inferolateral wall in a 15 years old patient after recovery of 5FU-related cardiogenic shock
Acknowledgements
We thank Dr Dr Christine Le Beller, unité de pharmacovigilence, hôpital européen Georges Pompidou for her help in the management of these two cases. We are indebted towards Dr Gilles Soulat, hôpital européen Georges Pompidou, for the cMR images.
Authors have no disclosures.
References
1. Polk A, Vaage-Nilsen M, Vistisen K, Nielsen DL. Cardiotoxicity in cancer patients treated with 5-fluorouracil or capecitabine: a systematic review of incidence, manifestations and predisposing factors.Cancer Treat Rev 2013;39(8):974-84.
2. McEvilly M, Popelas C, Tremmel B. Use of uridine triacetate for the management of fluorouracil overdose. Am J Health Syst Pharm2011;68(19):1806-9.
3. Meulendijks D, Henricks LM, Amstutz U, et al. Rs895819 in MIR27A improves the predictive value of DPYD variants to identify patients at risk of severe fluoropyrimidine-associated toxicity. Int J Cancer2016;138(11):2752-61.
4. Ma WW, Saif MW, El-Rayes BF, et al. Emergency use of uridine triacetate for the prevention and treatment of life-threatening 5-fluorouracil and capecitabine toxicity. Cancer2017;123(2):345-356.
5. Mirabel M, Luyt CE, Leprince P, Trouillet JL, Aubert S, Léger P, Pavie A, Chastre J, Combes A. Outcomes, Long-term Quality-of-Life and Psychological Assessment of Fulminant Myocarditis Patients Rescued by Mechanical Circulatory Support, Crit Care Med 2011, 39:1029 –1035.