Intersection of Cardiology and Oncology Clinical Practices

INTRODUCTION Globally, cancer is diagnosed in approximately 13 million people each year. Approximately 1.6 million cancer patients are seen by cancer clinics across the United States (US) at this time. Over the next two decades, cancer incidence is estimated to increase by approximately 45% to 2.3 million (1). In the US, the 5-year relative survival rate of patients diagnosed with cancer in 1975–1977 was 50%, improving to 68% in the period 1999–2005. Novel targeted chemotherapeutic agents and improved diagnostic techniques are responsible for this increased survival. However, with the improvement in life expectancy, the adverse effects of chemotherapeutic agents, especially cardiotoxicity, is an emerging health problem. Cardiovascular toxicity on its own has a detrimental effect on both the quantity and quality of life independent of the oncological prognosis. Currently, more than two million women with breast cancer are at risk of anthracycline cardiotoxicity in the US (2). Human epidermal growth factor receptor II (HER2) positive disease comprises approximately 25% of all breast cancer patients and is associated with more aggressive disease activity and worse prognosis. Trastuzumab, a humanized monoclonal antibody used for patients with HER2 positive breast cancer in conjugation with chemotherapy, can provide longer survival and 20% reduction in risk of death (3). Cardiotoxicity becomes an important health issue because up to 27% of women with breast cancer receiving anthracyclines, cyclophosphamide, and trastuzumab showed cardiac dysfunction (3). Breast cancer mortality is reduced by approximately one-third, but the risk of heart toxicity is five times more likely for women receiving trastuzumab than women receiving standard therapy alone (4). Patients showing signs of cardiotoxicity often require a dose reduction, a change in the schedule dosing or even cessation of treatment with attendant consequences. Many patients with an asymptomatic decrease in left ventricular ejection fraction (LVEF) are receiving neither the American College of Cardiology/American Heart Association Class I-indicated treatments nor cardiovascular specialty consultation (5). Concern for cardiotoxicity is not restricted to breast cancer survivors. Based on National Cancer Institute (NCI) data, the number of new renal cancer patients in 2013 is expected to be 65,000. In Europe, the incidence of renal cell carcinoma (RCC) has doubled in the last three decades (6). Improved treatment strategies have increased the 5-year survival of patients with RCC from 50% in 1975–1977 to 72% in 2002–2008. Within the last decade, the US Food and Drug Administration (FDA) has approved six drugs for the treatment of RCC including multitargeted tyrosine kinase inhibitors (TKIs); antibodies to vascular endothelial growth factor (VEGF); and mammalian target of rapamycin (mTOR) inhibitors. Sunitinib, a novel multitargeted TKI, has proven efficacy in advanced metastatic RCC demonstrating an increased median progression free survival of 8.3 months in these patients (7). In a study by Hall et al. (8), five of the approved targeted therapy drugs (sorafenib, pazopanib, bevacizumab, everolimus, and temsirolimus) have cardiotoxic side effects. In this 159patient study, 73% of patients experienced some form of cardiotoxicity ranging from hypertension to severe heart failure (8). In a cohort of patients with renal and nonrenal carcinoma, sunitinib was found to be associated with a 3.3-fold higher risk of heart failure (9). Other targeted agents such as imatinib mesylate, Dasatinib, Nilotinib, and Sorafenib are prescribed for treatment of various hematological malignancies, hepatocellular carcinoma (HCC), gastrointestinal stromal tumor (GIST), and myeloproliferative/myelodysplastic diseases and have been shown to be strongly associated to cardiotoxicity (10–13). Imatinib has been shown to be associated with decline in LVEF, especially in patients with other comorbidities including coronary artery disease, diabetes, and hypertension (10).