Journal of Cancer Research and Clinical Oncology

, Volume 134, Issue 1, pp 75–82

Cardiotoxicity of fluoropyrimidines in different schedules of administration: a prospective study

Authors

    • Department of Medicine, 2nd Division of Medical Oncology“Metaxa” Cancer Hospital, Piraues
  • Manolis S. Kallistratos
    • Department of Medicine, 2nd Division of Medical Oncology“Metaxa” Cancer Hospital, Piraues
  • Petros Kopterides
    • Department of Pathophysiology, Oncology UnitAthens University School of Medicine, Laikon General Hospital
  • John Syrios
    • Department of Pathophysiology, Oncology UnitAthens University School of Medicine, Laikon General Hospital
  • Helias Skopelitis
    • Department of Pathophysiology, Oncology UnitAthens University School of Medicine, Laikon General Hospital
  • Nicolaos Mylonakis
    • Department of Medicine, 2nd Division of Medical Oncology“Metaxa” Cancer Hospital, Piraues
  • Athanasios Karabelis
    • Department of Medicine, 2nd Division of Medical Oncology“Metaxa” Cancer Hospital, Piraues
  • Nicolas Tsavaris
    • Department of Pathophysiology, Oncology UnitAthens University School of Medicine, Laikon General Hospital
Original Paper

DOI: 10.1007/s00432-007-0250-9

Cite this article as:
Kosmas, C., Kallistratos, M.S., Kopterides, P. et al. J Cancer Res Clin Oncol (2008) 134: 75. doi:10.1007/s00432-007-0250-9

Abstract

Background

Cardiotoxicity associated with 5-Fluorouracil (5FU) administration has been infrequently reported in literature, albeit various series of acute coronary syndromes have recorded a low but definite incidence of the above toxicity. In the present study, patients undergoing 5FU-based and oral capecitabine (Xeloda®)-based chemotherapy were tested for the potential development of cardiac-related symptoms during their administration.

Patients and methods

Six hundred and forty-four patients entered the study. Those experiencing any cardiac-related symptoms during 5FU infusion or oral capecitabine were subjected to ECG and serum cardiac enzymes determination. If cardiotoxicity was confirmed, 5FU infusion or oral capecitabine were interrupted, sublingual nitrates administered and cardiac monitoring initiated, while patients with >two-fold enzyme elevation were followed in a coronary care unit for at least 72 h. Cases with acute myocardial infarction were excluded from further 5FU or oral capecitabine treatment.

Results

Overall 26 patients (4.03%) developed symptoms and/or ECG abnormalities due to 5FU and capecitabine. Patients with continuous 5FU infusion presented a higher incidence of cardiotoxicity [14/209; 6.7%, 95% confidence interval (CI) = 3.3–10.1%] than the remaining (7/317; 2.3%, 95% CI = 0.8–3.3%) (P < 0.012). Specifically, an increased incidence of cardiac-related events was encountered in patients with continuous 24-h 5FU + LV infusion for 5 days (12.5%, 95% CI = 2.3–22.7%) rather than in patients with the same schedule without LV (5.3%, 95% CI = 1.95–8.67%) (P < 0.027), as well as in patients with short 5FU + LV administration (2.4%, 95% CI = 0.9–3.9%) (P < 0.019). Overall, 3/54 patients (5.5%, 95% CI = −0.6–11.1%) on oral capecitabine developed cardiac-related events. Seven out of the 20 patients suffered an acute myocardial infarction, 6 developed ischemia only, while 4 more patients had ECG consistent with coronary vasospasm and 3 with conduction disturbances, of which one subsequently died. Patients administered oral capecitabine had a similar incidence of cardiac-related events; 1/22 (4.5%) patients with advanced breast cancer and 2/32 (6.2%) with colorectal cancer.

Conclusions

The present study supports the toxic effect of 5-FU on the myocardium, which is largely schedule-dependent, whereas a low but finite risk of such toxicity has been observed with oral capecitabine. A high level of alertness is required when using fluoropyrimidines (i.v. 5FU or oral capecitabine), while their toxic effect on the coronary endothelium and myocardium merits further investigation.

Keywords

FluorouracilCapecitabineChemotherapyCardiotoxicity

Copyright information

© Springer-Verlag 2007