5-Fluorouracil Rechallenge After Cardiotoxicity

Abstract

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.

Figure 1.

(A) ECG strip showing ventricular fibrillation converting to monomorphic ventricular tachycardia after DC cardioversion. (B) 12-Lead ECG showing ST-elevation in the inferior leads with reciprocal ST-depression. (C) 12-Lead ECG showing atrial fibrillation with nonspecific ST-T changes.

Figure 2.

(A–D) Cardiac catheterization showing clean coronary arteries with no evidence of significant atherosclerosis.