Clinical Cardiotoxicity of 5‐Fluorouracil

Abstract

5-Fluorouracil is widely known to be toxic to the hematopoietic and gastrointestinal systems. It also has cardiac toxicity, but this is perceived to be rare. During a 16-month period from January 1990 through April 1991, approximately 910 patients were treated with 5-fluorouracil. Five of these developed life-threatening toxicity consistent with coronary artery spasm for an incidence of .55%. The acute events occurred on the third or fourth day of the 5-day infusion and after the fourth intravenous bolus in the patient on bolus therapy. Each of the patients had ST elevation and ventricular arrhythmias, four had acute myocardial infarction, and two had cardiac arrests. In these cases and those previously reported, cardiac toxicity is consistent with drug- or metabolite-mediated increases in coronary vasomotor tone and spasm, leading to the full spectrum of signs and symptoms of myocardial ischemia in susceptible individuals.

ACC/AHA/ESC 2006 Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death

“…Ephedrine, the active component, is also detected in a number of street drugs. Coronary spasm has been reported with multiple other medications and can present as VF: certain anticancer drugs (5-fluorouracil [1079][1080][1081][1082]), capecitabine (1083), triptans used in the treatment of migraines (1084), recreational agents (e.g., ecstasy [1085], cocaine), inadvertent vascular administration of pressor catecholamines, and anaphylaxis due to any one of a wide range of drugs (see Section 7.5 for further discussion).…”

Angina Pectoris und ST-Hebungen nach Chemotherapie mit 5-FU

“…Lebensbedrohliche Ereignisse traten in einer bemerkenswert hohen Zahl mit einer Mortalität von 2,2% auf. Eine andere Arbeitsgruppe beobachtete an 910 Patienten, die über 16 Monate mit 5-FU behandelt wurden, in 0,55% der Fälle gravierende kardiale Nebenwirkungen (Myokardinfarkte, ventrikuläre Tachykardien und Asystolien; [7]). Eine weitere Arbeit mit 417 Patienten berichtete eine Kardiotoxizität von 4%, wobei sich 41% dieser Patienten mit einem akuten Myokardinfarkt und weitere 23% mit deutlichen Ischämiezeichen im EKG ohne Enzymanstieg präsentierten [13].…”

Severe Cardiotoxicity of High-Dose 5-Fluorouracil in Combination with Folinic Acid, Cisplatin and Methotrexate in a 14-Year-Old Boy with Nasopharyngeal Carcinoma (Schmincke Tumor)

“…There was no indication for one of the cardioprotective drugs proposed for elderly patients, such as dipyramidole, nitroglycerin, diltiazem or Ca channel blockers [3], In our patient the clinical symptoms were those de scribed as typical by other authors [2,3,[11][12][13] suggestive of cardiac ischemia or myocardial infarction. The labora tory evaluation for myocardial enzymes, troponin T and myosin was negative.…”