title: Cardiotoxicity following different doses and schedules of 5-fluorouracil administration for malignancy -- a survey of 427 patients.
abstract: 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.
authors.affiliation: Department of Pathophysiology, Oncology Unit, Laikon General Hospital, Athens University School of Medicine, Greece. ckosm@ath.forthnet.gr
authors.forename: Nicolas
authors.initials: N
authors.lastname: Tsavaris
authors.forename: Christos
authors.initials: C
authors.lastname: Kosmas
authors.forename: Maria
authors.initials: M
authors.lastname: Vadiaka
authors.forename: Michalis
authors.initials: M
authors.lastname: Efremidis
authors.forename: Andreas
authors.initials: A
authors.lastname: Zinelis
authors.forename: Dimitris
authors.initials: D
authors.lastname: Beldecos
authors.forename: Dimitris
authors.initials: D
authors.lastname: Sakelariou
authors.forename: Christos
authors.initials: C
authors.lastname: Koufos
authors.forename: George
authors.initials: G
authors.lastname: Stamatelos
mesh_terms: 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
chemical_list: D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil