Nebivolol effect on doxorubicin-induced cardiotoxicity in breast cancer

Flavia Cochera,* Daniel Dinca,* Diana Aurora Bordejevic, Ioana Mihaela Citu, Adelina Marioara Mavrea, Minodora Andor, Mihai Trofenciuc, Mirela Cleopatra Tomescu Cardiology Department, “Victor Babes” University of Medicine and Pharmacy, Timisoara, Romania *These authors contributed equally to this work Purpose: The aim of this study was to assess whether nebivolol treatment could have beneficial effects in the prevention of anthracyclines-induced cardiotoxicity. Patients and methods: Our prospective study included 60 women, mean age 52.6±13 years, with HER2 negative breast cancer, scheduled to undergo treatment with doxorubicin. The patients were randomly divided into two groups: the treatment group (n=30) which received nebivolol 5 mg once daily for the duration of chemotherapy and the control group (n=30) without treatment with nebivolol. Cytostatic treatment was performed with doxorubicin 70 mg/m2 administered intravenously every 21 days for six cycles. The average cumulative dose of doxorubicin was 520±8 mg/m2. Echocardiography was performed immediately before and after six cycles of doxorubicin therapy. Results: We found no significant differences between the two groups regarding baseline clinical and echocardiographic parameters. The two groups reached a similar cumulative dose of doxorubicin. No patient died during the study. None of the patients withdrew from chemotherapy. After six cycles of doxorubicin therapy, the left ventricular (LV) ejection fraction, shortening fraction, and LV diameters changed, but not significantly. Tissue Doppler imaging (TDI) detected in the control group a significant decrease of myocardial velocities, indicating a LV diastolic dysfunction. In the same group, speckle tracking imaging (STI) revealed a statistically significant alteration of the ventricular deformation, which means a decrease in LV systolic function. In the nebivolol treatment group, no significant alterations in the LV systolic and diastolic function were observed. Conclusion: The results of this study show the benefit of new echocardiographic imaging methods such as TDI and STI in the screening of early cardiac dysfunction induced by cytostatic treatment. Nebivolol treatment prevented the occurrence of anthracyclines-induced cardiomyopathy in the short term. In order to confirm these preliminary results, larger studies with a longer follow-up period are required. Keywords: breast cancer, doxorubicin, nebivolol, echocardiography, cardiotoxicity, cardioprotectio

Cardiovascular and Central Nervous System Toxicity by Anticancer Drugs in Breast Cancer Patients

Breast cancer is one of the most malignant diseases, associated with high rate mortality. In this chapter a particular attention is paid on cardiovascular and central nervous system toxicity induced by chemotherapeutic agents used for both primary and metastatic treatment of this life-threatening pathology. With respect to traditional drugs, including anthracyclines, taxanes, and fluoropyrimidines, the more recent targeted therapies, such as human epidermal growth factor receptor 2 (HER2) and vascular endothelial growth factor (VEGF), aimed to ameliorate anticancer activity and to reduce toxic effects by affecting more specific molecular sites. However, despite the improvement in breast cancer treatment, these novel drugs were also found to be associated, even if at a lesser extent, with important side effects, such as cardiotoxicity, with consequent heart failure. For this reason, the cardiovascular and brain safety profile of all anticancer drugs and protocols remains important items to be carefully evaluated in breast cancer patients