Capecitabine-induced cardiotoxicity: more evidence or clinical approaches to protect the patients' heart?

Caterina Fontanella,1 Marianna Aita,1 Marika Cinausero,1 Giuseppe Aprile,1 Maria Grazia Baldin,2 Veronica Dusi,3 Chiara Lestuzzi,4 Gianpiero Fasola,1 Fabio Puglisi1,5 1Department of Oncology, University Hospital of Udine, Udine, Italy; 2Department of Cardiology, Palmanova General Hospital, Palmanova, Italy; 3Department of Cardiology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; 4Department of Cardiology, Centro di Riferimento Oncologico, National Cancer Institute, Aviano, Italy; 5Department of Medical and Biological Sciences, University of Udine, Udine, Italy Abstract: Fluoropyrimidines, such as capecitabine and 5-fluorouracil, may cause cardiac toxicity. In recent years, the incidence of this side effect has increased and it is expected to further rise due to the population aging and the disproportionate incidence of breast and gastrointestinal cancers in older individuals. The spectrum of cardiac manifestations includes different signs and symptoms and the diagnosis may be difficult. Here, we report the case of a 43-year-old woman with advanced breast cancer who was rechallenged with a capecitabine-based regimen after experiencing a cardiac adverse event during the first fluoropyrimidine exposure. This real-practice case serves as a springboard for discussion about the current evidence on differential diagnosis of capecitabine-related cardiac toxicity, its risk factors, and the underpinning mechanisms of early onset. Moreover, we discussed whether a rechallenge with fluoropyrimidines could be safe in patients who had experienced a previous cardiac adverse event. Keywords: risk factors, clinical manifestation, rechallenge