[Cardiotoxicity of continuous intravenous infusion of 5-fluorouracil: clinical study, prevention and physiopathology. Apropos of 13 cases]

Abstract

5-Fluorouracil (5FU) cardiotoxicity is thought to be an infrequent toxic effect, usually related to coronary vasospasm. Among 198 patients (pts) receiving 5FU as a continuous infusion (CI) over 96 or 120 h, at a daily dose of 1,000 mg/m2, 13 new cases of 5FU--cardiotoxicity are reported. In all cases but 1, cardiovascular symptoms occurred at the first 5FU-CI course, with mean time of onset of 3 d. Chest pain was the prominent inaugural symptom with angor pectoris (6 pts) and pericarditis (3 pts). Five pts developed cardiogenic shock, which was irreversible in 3 cases. The severity of such an evolution requires prompt 5FU discontinuation, if symptoms occur, and careful hemodynamic supervision during 5FU therapy. One patient experienced typical myocardial infarction, another one epicardo myocardiopathic process with adiastolia. Disorders of repolarisation on electrocardiographic tracing were the prominent abnormalities, associated with a significant increase of QT segment in 3 cases. Re-introduction of 5FU-CI resulted in chest pain recurrence in 2 out of 4 pts, despite calcium antagonist "prevention". In our retrospective study, the incidence of 5FU-CI cardiotoxicity is 6.5%, which is consistent with recent reports (10%). Whether 5FU-induced cardiotoxicity mechanism is related to vasospastic or direct effect remains unclear. However, our series suggests a 5FU-induced post ischaemic myocardial dysfunction as described in the "stunned myocardium" syndrome.