Incidence and risk factors for capecitabine-induced symptomatic cardiotoxicity: a retrospective study of 452 consecutive patients with metastatic breast cancer

OBJECTIVES Case reports of capecitabine cardiotoxicity resemble those seen with intravenous 5-fluorouracil (5-FU) with chest pain as the predominant manifestation, but few studies of capecitabine cardiotoxicity are available. We aimed to determine the incidence of symptomatic cardiotoxicity from capecitabine in patients with breast cancer and to identify risk factors. METHODS We reviewed medical records of consecutive women with breast cancer treated with capecitabine (1000 mg/m2 two times per day) from 2002 to 2012 at one institution. RESULTS 22 of 452 patients (4.9%) (95% CI 2.9% to 6.9%) had symptoms of cardiotoxicity (chest pain: n=13, dyspnoea: n=9, palpitations: n=2). 11 patients had changes on ECG (atrial fibrillation: n=5, ST deviations: n=3, T-wave abnormalities: n=2 and QTc prolongation: n=1). 2 patients (0.4%) sustained acute myocardial infarction. 1 patient (0.2%) developed cardiac arrest with lethal outcome. 4 of 6 patients (66%) retreated with capecitabine had recurrent symptoms at retreatment. Cardiac comorbidity (p=0.001), hypercholesterolaemia (p=0.005) and current smoking (p=0.023) were risk factors for cardiotoxicity in univariate analyses and remained significant when adjusted for age. Patients with cardiac comorbidity were 5.5 times (95% CI 2.0 to 14.8) more likely to develop cardiotoxicity. In the subgroup of patients with apparently no cardiac comorbidity, the incidence of cardiotoxicity was lower (3.7%) and hypercholesterolaemia (p=0.035) and current smoking (p=0.020) were risk factors of cardiotoxicity. CONCLUSIONS The incidence of cardiotoxicity from capecitabine resembles that of intravenous 5-FU (≈5%). Cardiac comorbidity, hypercholesterolaemia and current smoking were associated with development of cardiotoxicity.