Cardiac Toxicity in Patients with Metastatic Renal Cell Carcinoma Receiving Tyrosine Kinase Inhibitors

Posted on March 8th, 2009 by

Cardiac Toxicity in Patients with Metastatic Renal Cell Carcinoma Receiving Tyrosine Kinase Inhibitors

In a recent single-center study, researchers analyzed the cardiac toxicity associated with the tyrosine kinase inhibitors Sutent® (sunitinib) and Nexavar® (sorafenib) in patients with metastatic renal cell carcinoma and concluded that although the incidence of cardiac damage from these agents may be higher than previously thought, it is manageable with careful monitoring and treatment. The results of this study were published in the November 10, 2008 issue of the Journal of Clinical Oncology.[1]

The kidneys are each filled with tiny tubules that clean and filter the blood-the process that removes waste and makes urine. Renal cell carcinoma (RCC) is a malignancy involving these tubules of the kidney and is the most common type of kidney cancer. Metastatic RCC refers to cancer that has spread from the kidney to distant sites in the body.

Researchers continue to evaluate novel therapeutic strategies, such as targeted therapies, for the treatment of metastatic RCC. A targeted therapy is one that is designed to treat only the cancer cells and minimize damage to normal, healthy cells. Sutent and Nexavar are targeted therapy agents referred to as tyrosine kinase inhibitors (TKIs) that block the growth of cancer cells by inhibiting several biological pathways that are involved in cellular replication and spread. The use of TKIs has increased dramatically in recent years both because of their clinical effectiveness and because they are oral agents that are easy to administer; however, researchers are still learning about the cardiac toxicity related to these agents and new research is beginning to indicate that targeted therapies may actually impact healthy cells more than previously thought.

This study was an observational, single-center study analyzing the cardiac side effects in 74 patients treated with TKIs. The researchers had three goals: 1) to investigate the signs of cardiac damage in patients receiving TKIs, 2) to study the reversibility of cardiac events with classical cardiovascular treatments, and 3) to determine the feasibility of continuing TKI treatment despite the occurrence of cardiac events.

Prior to beginning treatment with a TKI, all patients were analyzed for coronary artery disease (CAD) risk factors, history or evidence of CAD, hypertension (high blood pressure), rhythm disturbances, and heart failure. Select patients underwent echocardiography (ECG) at baseline. All patients who experienced a cardiac event during treatment underwent ECG. (A cardiac event was defined as the occurrence of increased enzymes if normal at baseline, symptomatic arrhythmia that required treatment, new left ventricular dysfunction, or acute coronary syndrome.)

During treatment, 33.8% of patients experienced a cardiac event, 40.5% had ECG changes, and 18% were symptomatic. All symptomatic patients interrupted their TKI treatment to undergo the appropriate cardiovascular treatment. Seven of these patients (9.4%) were seriously compromised and required intermediate care and/or intensive care. After undergoing cardiovascular treatment, these patients reinitiated TKI treatment and had permanent cardiovascular inpatient monitoring for two weeks.

All patients recovered after cardiovascular management and were considered eligible to continue TKI treatment. The researchers concluded that “cardiac damage from TKI treatment is a largely underestimated phenomenon, but is manageable if patients have careful cardiovascular monitoring and cardiac treatment at the first signs of myocardial damage.” They stress the importance of integrating cardiology treatment into the treatment protocol.

Research is ongoing to evaluate the side effects of targeted agents. Patients receiving treatment with a TKI are encouraged to discuss their individual risks and benefits with their physician.

Reference:


[1] Schmidinger M, Zielinski CC, Vogl UM, et al. Cardiac toxicity of Sunitinib and Sorafenib in patients with metastatic renal cell carcinoma. Journal of Clinical Oncology. 2008;26:5204-5212.

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