Cardiotoxicity from Capecitabine Chemotherapy: Prospective Study of Incidence at Rest and During Physical Exercise

Chiara Lestuzzi, Davide Stolfo, Antonino De Paoli, Alberto Banzato, Angela Buonadonna, Ettore Bidoli, Lucia Tartuferi, Elda Viel, Giulia De Angelis, Sara Lonardi, Roberto Innocente, Massimiliano Berretta, Francesca Bergamo, Alessandra Guglielmi, Gianfranco Sinagra, Joerg Herrmann

Research output: Contribution to journalArticlepeer-review


Background: Physical activity may increase the risk of cardiotoxicity (myocardial ischemia, major arrhythmias) of 5-Fluorouracil, but this risk has never been investigated for its prodrug capecitabine. Patients and Methods: One hundred and ninety-two consecutive patients undergoing capecitabine chemotherapy from December 1, 2010 through July 31, 2016 were prospectively evaluated. The baseline evaluation included electrocardiography (ECG) and echocardiography (2DE); a follow-up evaluation, including ECG and exercise stress testing (2DE in case of ECG abnormalities), was done after ≥10 days of treatment. Cardiotoxicity was suspected from ischemic ECG changes, new kinetic abnormalities at 2DE, Lown classification ≥2 ventricular arrhythmia, symptomatic arrhythmias, or positive stress test, and confirmed by a negative stress test after capecitabine washout. Results: Cardiotoxicity was diagnosed in 32 patients (16.7%): six at rest and 26 during exercise. All 32 patients had ECG abnormalities: ST-segment changes (24 patients), negative T-waves (2) and/or arrhythmias: ventricular arrhythmias (14 cases), supraventricular tachycardia (2), complete heart block (1). Eight patients had typical symptoms, 6 had atypical symptoms, 1 had syncope, 17 (53%) were asymptomatic. Cardiotoxicity was more common in patients with atypical symptoms during daily life (OR = 15.7) and in those on a therapeutic schedule of 5 days/week (OR = 9.44). Conclusion: Capecitabine cardiotoxicity is frequent, and often elicited by physical effort. Oncologists, cardiologists, and general practitioners should be aware of this risk. Active cardiotoxicity surveillance with ECG (and echocardiogram and/or stress testing in suspected cases) during therapy is recommended.

Original languageEnglish (US)
Pages (from-to)E158-E167
Issue number2
StatePublished - Feb 2022


  • arrhythmias
  • capecitabine
  • cardiotoxicity
  • chemotherapy
  • ischemia
  • stress test

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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