Author + information
- Received August 9, 2012
- Revision received August 20, 2012
- Accepted August 21, 2012
- Published online February 1, 2013.
- ↵∗Reprint requests and correspondence:
Dr. Ronald M. Witteles, Division of Cardiovascular Medicine, Stanford University School of Medicine, 300 Pasteur Drive, Falk Cardiovascular Research Center #273, Stanford, California 94305-5406.
Objectives The purpose of this study was to document the incidence and extent of cardiovascular toxicity among advanced renal cell carcinoma patients treated with newer targeted cancer agents.
Background The potential for targeted cancer agents to induce cardiovascular toxicity has been increasingly recognized, but the overall incidence and extent of toxicity have not been well characterized. Early detection of asymptomatic patients could preempt symptomatic toxicity and reduce treatment-related morbidity and mortality.
Methods The incidence of hypertension, left ventricular dysfunction, and heart failure was assessed for all advanced renal cell carcinoma patients treated with targeted therapies at our institution between 2004 and 2011. Grading was performed according to the Common Terminology Criteria for Adverse Events version 4.0.
Results Cardiovascular toxicity developed in 116 of 159 patients (73%), including 52 of 159 patients (33%) when hypertension was excluded. Toxicity varied from occurrences of asymptomatic drops in left ventricular ejection fraction to rises in N-terminal-pro-B-type natriuretic peptide to severe heart failure. The tyrosine kinase inhibitor sunitinib was the agent most frequently used, with 66 of 101 sunitinib-treated patients (65%) developing a form of cardiovascular toxicity, including 32 of 101 patients (32%), excluding hypertension. Other VEGF inhibitors such as bevacizumab, sorafenib, and pazopanib also elicited significant cardiovascular toxicity with incidences ranging from 51% to 68%.
Conclusions The frequency and severity of cardiovascular toxicity in advanced renal cell carcinoma patients treated with targeted cancer therapies are high.
Dr. Harshman serves on an advisory board for Pfizer and Novartis; and has received research funding from BMS, Novartis, and Genentech. Dr. Srinivas serves on an advisory board for Pfizer, Genentech, and Novartis; and has received research funding from GlaxoSmithKline, Aveo, Novartis, and Genentech. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received August 9, 2012.
- Revision received August 20, 2012.
- Accepted August 21, 2012.
- American College of Cardiology Foundation