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Medical Science Monitor Basic Research


5-Fluorouracil Rechallenge After Cardiotoxicity

Unusual clinical course, Challenging differential diagnosis, Unusual or unexpected effect of treatment, Diagnostic / therapeutic accidents, Adverse events of drug therapy

Aakash Desai, Turab Mohammed, Kunal N. Patel, Mansour Almnajam, Agnes S. Kim

USA Department of Medicine, University of Connecticut Health, Farmington, CT, USA

Am J Case Rep 2020; 21:e924446

DOI: 10.12659/AJCR.924446

Available online: 2020-07-29

Published: 2020-08-29


BACKGROUND: 5-Fluorouracil (5-FU) is a widely used intravenous chemotherapy agent that is highly effective in the treatment of a variety of solid malignancies. Cardiotoxicity related to 5-FU is a complex clinical entity associated with significant morbidity and mortality. Whether a patient who experienced a major cardiac side effect from 5-FU can be safely rechallenged with this drug is a clinical dilemma.
CASE REPORT: We present the case of a patient with stage III colorectal adenocarcinoma who experienced ventricular fibrillation during the first cycle of FOLFOX (5-FU, folinic acid, and oxaliplatin) regimen in the adjuvant setting. Post-resuscitation electrocardiogram revealed ST-elevation in the inferior leads with reciprocal changes. Coronary angiogram revealed no obstructive coronary artery disease. Cardiac workup led to the conclusion of probable fluorouracil-induced vasospasm as the cause of his cardiac arrest. He received implantable cardioverter defibrillator. The decision was made to hold 5-FU. At 3-month follow-up, there was evidence of progressive metastasis. After comprehensive risk-benefit discussions, the decision was made for palliative chemotherapy using 5-FU/leucovorin. A pre-treatment regimen including isosorbide dinitrate, diltiazem, and metoprolol was used. The patient tolerated 5-FU rechallenge without recurrent cardiovascular complication.
CONCLUSIONS: The cardiotoxicity profile of 5-FU can range from anginal chest pain to sudden cardiac death. When considering 5-FU rechallenge, clinicians should adopt a multidisciplinary approach, favor using prophylactic antianginal therapy, change to bolus dosing, and use continuous telemetry monitoring. Screening patients for dihydropyrimidine dehydrogenase deficiency prior to 5-FU administration may facilitate an individualized strategy for optimal dosing and safety.

Keywords: Cardiotoxins, Coronary Vasospasm, Dihydropyrimidine Dehydrogenase Deficiency, Fluorouracil