5-Fluorouracil Rechallenge After Cardiotoxicity

Abstract

Patient: Male, 66-year-old Final Diagnosis: Colon adenocarcinoma • ventricular arrhythmia Symptoms: Cardiac arrest • syncope Medication: — Clinical Procedure: Cardiac catheterization • Cardiac Electronic Implantable Device (CEID) Specialty: Cardiology • General and Internal Medicine • Oncology Objective: Unusual clinical course 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.

IL6/STAT Signaling Pathway and PPARα are Involved in Mediating the dose Dependent Cardioprotective Effect of Fenofibrate in 5-fluorouracil induced Cardiotoxicity

“…In the present study, 5FU treated rats showed a signi cant elevation in the activity of serum CK-MB, LDH, ALT, AST levels indicating 5FU induced myocardial necrotic damage and the leakiness of the plasma membrane. This is in accordance with Lamberti et al 1 ; Desai et al 22 .…”

Coronary atherosclerosis and chemotherapy: From bench to bedside

“…Early studies have identified the effects of 5-FU on the coronary arteries, and knowledge about its cardiovascular toxicity and adverse effects on the coronary arteries has improved with advances in treatments. The incidence of cardiovascular toxicity caused by 5-FU ranges from 2% to 18% ( 51 , 52 ). Another retrospective analysis summarized the mortality risk from the cardiovascular adverse effects of 5-FU.…”

Invasive Evaluation for Coronary Vasospasm

“…Various drugs can also induce CAS, including psychostimulants, vasoconstricting agents, and immunosuppressive medications, such as calcineurin inhibitors and fluorouracil. 13,23 Myocardial bridging is an anatomical variant in which the epicardial coronary arteries pass through cardiac muscle layers and become compressed during systole. Montone et al found that patients with this condition are more likely to have a positive acetylcholine test and it may be a predictor of MINOCA.…”