Capecitabine in Breast Cancer: the issue of cardiotoxicity during fluoropyrimidine treatment

Capecitabine is an orally available fluoropyrimidine carbamate that selectively delivers fluorouracil (5-FU) to tissues expressing high levels of thymidine phosphorylase (TP) such as tumors. The drug has demonstrated efficacy in metastatic breast cancer, colorectal, and pancreatic cancer. Although these are considered safe drugs, a growing body of literature reports adverse cardiac effects. Clinical trials indicate that capecitabine has a cardiac toxicity similar to that of infused fluoropyrimidines such as 5-FU. Here, we review cardiotoxicity in the use of fluoropyrimidines, with particular attention toward capecitabine. We also describe a severe, reversible cardiac event that occurred in a 39-year-old woman, with no cardiac risk factors, treated with capecitabine for advanced breast cancer. This review and our experience confirm that fluoropyrimidine cardiotoxicity is an infrequent but documented side effect. Oncology patients under treatment should be closely observed and monitored for cardiac symptoms with particular attention in case of signs or symptoms of cardiovascular complications. The implementation of cardio-oncology interdisciplinary teams should, in the future, reduce the impact of cancer treatment\u2013associated cardiotoxicity syndromes

n-3 polyunsaturated fatty acids and atrial fibrillation in patients with chronic heart failure: the GISSI-HF trial.

AIMS: In the last few years, n-3 polyunsaturated acids (PUFAs) have been extensively studied for the prevention of AF, mostly in patients without heart failure (HF) or LV dysfunction. This post-hoc analysis of the GISSI-HF trial assessed the effect of n-3 PUFAs on AF in patients with chronic HF without AF at study entry over a median follow-up of 3.9 years. METHODS AND RESULTS: In the GISSI-HF trial, 6975 patients with chronic HF were randomized to 1 g daily of n-3 PUFAs or placebo on top of recommended therapy for HF. Of these, 1140 (16.3%) had AF at baseline ECG and were excluded from the present analysis. AF during the trial was defined as the presence of AF on the ECGs done at each visit during the trial or AF as a cause of worsening HF or hospital admission or as an event during hospitalization. Dietary fish consumption and the circulating levels of n-3 PUFAs (the latter in a subset of 1203 patients) were also available. Among the 5835 patients without AF at study entry, 444 randomized to n-3 PUFAs (15.2%) and 408 to placebo (14.0%) developed AF (unadjusted hazard 1.10, P = 0.19). Lower circulating n-3 PUFA levels were independently associated with higher AF prevalence at study entry, but not with its new occurrence. CONCLUSIONS: Despite an inverse relationship between plasma n-3 PUFA levels and prevalent AF, this study found no evidence that 1 g daily n-3 PUFA supplementation in patients with chronic HF reduces incident AF