Cardiotoxicity following different doses and schedules of 5-fluorouracil administration for malignancy -- a survey of 427 patients.

BACKGROUND: Although cardiotoxicity associated with 5-Fluorouracil (5-FU) administration is infrequent, there are case reports of acute coronary syndromes. We report on patients undergoing 5-FU chemotherapy who developed cardiac symptoms during its administration. MATERIAL/
METHODS: In patients receiving 5-FU who experienced cardiac-related symptoms, ECG and serum cardiac enzyme determination were performed. If cardiotoxicity was detected, 5-FU infusion was interrupted, and the patients received sublingual nitrates and cardiac monitoring, while patients with more than 2-fold elevated enzyme levels were monitored in a coronary care unit for at least 72 hours. In cases of acute myocardial infarction, 5-FU was terminated.
RESULTS: Of 427 patients entering the study, 17 (4%) developed clinical symptoms and ECG abnormalities indicating 5-FU cardiotoxicity. Patients with continuous infusion (c.i.) of 5-FU had a higher incidence of cardiotoxicity (12/197, 6%) than the remaining (5/235, 2.1%) (p=0.067), but more toxicity was encountered in patients with c.i. of 5-FU+LV for 24 hours for 5 days than in patients with the same regimen of 5-FU without LV (p<0.027) or patients with short 5-FU+LV administration (p=0.024). Seven of the 17 patients with 5-FU cardiotoxicity had an acute myocardial infarction, 4 developed ischemic changes, while 4 more patients had ECG abnormalities consistent with coronary vasospasm, of whom one subsequently died.
CONCLUSIONS: The present study supports the toxic effect of 5-FU on myocardium, which is largely schedule-dependent. Considerable vigilance is required when using this drug, and its toxic effect on the coronary endothelium and myocardium merit further investigation.