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.


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.
Tsavaris
Nicolas
N
Department of Pathophysiology, Oncology Unit, Laikon General Hospital, Athens University School of Medicine, Greece. ckosm@ath.forthnet.gr
Kosmas
Christos
C
Vadiaka
Maria
M
Efremidis
Michalis
M
Zinelis
Andreas
A
Beldecos
Dimitris
D
Sakelariou
Dimitris
D
Koufos
Christos
C
Stamatelos
George
G
D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004562:Electrocardiography; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects*; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000503:physiopathology
D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil