Incidence of myocardial ischemia during treatment with capecitabine: a cohort study with Holter recording and cardiac biomarkers.

Background and purpose: Treatment with fluoropyrimidines can lead to cardiotoxicity. For 5-fluorouracil, silent myocardial ischemia and effort-related myocardial ischemia have been demonstrated. We investigated the incidence of myocardial ischemia and clinical cardiotoxicity during treatment with capecitabine, a pro-drug of 5-fluorouracil.

Patients and methods: We included patients with breast- or colorectal cancer, who received first-time treatment with capecitabine. Holter recording, clinical evaluation, 12-lead electrocardiogram, and measurement of plasma cardiac troponin I and copeptin were performed before and during treatment.

Results: A total of 42 patients with breast cancer and 39 with colorectal cancer were included. Seven patients (9%) experienced clinical cardiotoxicity; five with unstable angina, one with dyspnoea, ST elevations and anterolateral hypokinesia, and one with cardiac arrest. Six patients (8%) had myocardial ischemia on Holter recording during treatment. Among these were two with clinical cardiotoxicity, and four (5.0%) with silent myocardial ischemia. More patients had myocardial ischemia on Holter recording during treatment compared to before, but the difference was not statistically significant (1st cycle: p = 0.22, 3rd/4th cycle: p = 0.50). Plasma copeptin increased during 1st cycle (p = 0.004), while cardiac troponin I remained unchanged (p = 0.92). More patients had non-sustained ventricular tachycardia during 1st cycle of treatment than before (p = 0.020).

Interpretation: Treatment with capecitabine was associated with an incidence of myocardial ischemia of 8%, an incidence of clinical cardiotoxicity of 9%, and an increase in plasma copeptin and the frequency of non-sustained ventricular tachycardia episodes. Increases in cardiac troponin I were rare. The incidence of myocardial ischemia was lower than previously reported for 5-fluorouracil.