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The frequency and severity of cardiovascular toxicity from targeted therapy in advanced renal cell carcinoma patients
Philip S Hall1, Lauren C Harshman2, Sandy Srinivas2
1Department of Internal Medicine, Stanford University School of Medicine, Stanford, California.
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.
Insights
Targeted cancer agents for advanced renal cell carcinoma frequently cause cardiovascular toxicity, including heart failure and left ventricular dysfunction. Early detection is crucial to manage these risks and improve patient outcomes.
Area of Science:
- Cardiology
- Oncology
- Pharmacology
Background:
- Cardiovascular toxicity is an emerging concern with targeted cancer therapies.
- The full scope of this toxicity in advanced renal cell carcinoma (RCC) patients is not well understood.
- Early identification of at-risk patients can prevent severe complications.
Purpose of the Study:
- To determine the incidence and severity of cardiovascular toxicity in advanced RCC patients receiving targeted agents.
- To characterize the types of cardiovascular adverse events associated with these therapies.
Main Methods:
- Retrospective analysis of advanced RCC patients treated with targeted therapies from 2004-2011.
- Assessment of hypertension, left ventricular dysfunction, and heart failure.
- Adherence to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for grading.
Main Results:
- Cardiovascular toxicity occurred in 73% of patients (116/159), or 33% excluding hypertension.
- Toxicity ranged from asymptomatic ejection fraction decline to severe heart failure.
- Tyrosine kinase inhibitors like sunitinib (65% incidence) and other VEGF inhibitors showed significant toxicity.
Conclusions:
- Advanced RCC patients treated with targeted therapies experience high rates of cardiovascular toxicity.
- The spectrum of toxicity is broad, impacting cardiac function and potentially leading to heart failure.
- These findings underscore the need for vigilant cardiovascular monitoring in this patient population.
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