Cardiac Toxicity of Sunitinib and Sorafenib in Patients With Metastatic Renal Cell Carcinoma

Purpose Sunitinib and sorafenib are tyrosine kinase inhibitors (TKIs) that have considerable efficacy in metastatic renal cell carcinoma. TKI-associated cardiotoxicity was reported in approximately 10% of the patients. Detailed cardiovascular monitoring during TKI treatment may reveal early signs of myocardial damage. Patients and Methods In this observational, single-center study, all patients intended for TKI treatment were analyzed for coronary artery disease (CAD) risk factors, history or evidence of CAD, hypertension, rhythm disturbances, and heart failure. Monitoring included assessment of symptoms, ECGs, and biochemical markers (ie, creatine kinase-MB, troponin T). Echocardiography was performed at baseline in selected patients and in all patients who experienced a cardiac event. 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. Results A total of 86 patients were treated with either sunitinib or sorafenib. Among 74 eligible patients, 33.8% experienced a cardiac event, 40.5% had ECG changes, and 18% were symptomatic. Seven patients (9.4%) were seriously compromised and required intermediate care and/or intensive care admission. All patients recovered after cardiovascular management (ie, medication, coronary angiography, pacemaker implantation, heart surgery) and were considered eligible for TKI continuation. Statistically, there was no significant survival difference between patients who experienced a cardiac event and those who did not experience a cardiac event. Conclusion Our observations indicate 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.

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Prospective cardiotoxicity screening during tyrosine kinase inhibitor therapy for renal cell carcinoma: An institutional experience

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e16003 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e16003-e16003

Author(s):

R. M. Witteles ◽

L. C. Harshman ◽

M. Telli ◽

S. Srinivas

Keyword(s):

Heart Failure ◽

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Troponin I ◽

Left Ventricular ◽

High Rate ◽

Heart Failure Therapy ◽

Screening Protocol ◽

Tki Treatment

e16003 Background: Tyrosine kinase inhibitors (TKI) can lead to cardiotoxicity either directly by causing left ventricular dysfunction, or indirectly by increasing blood pressure. In light of prior studies at our institution documenting a high rate of symptomatic heart failure in patients with renal cell carcinoma undergoing treatment with sunitinib, we instituted a prospective screening protocol to characterize the incidence and natural history of TKI-associated cardiotoxicity. Methods: From March-December 2008, patients receiving TKI therapy for renal cell carcinoma received cardiac biomarker screening (NT- BNP and Troponin I at baseline and after week 4 of each cycle) and transthoracic echocardiography (baseline, 1 month, 3 months, and every 3 months thereafter). If biomarkers were elevated or a decline in ejection fraction was observed, patients were referred for cardiology evaluation. Results: Twenty-six patients have been included since the protocol's initiation. No elevations in cardiac troponin I have been observed to date. Eight patients (31%) had elevations in NT-BNP (a sensitive marker for heart failure). The TKIs involved included sunitinib (5 patients), sorafenib (2 patients), and bevacizumab (1 patient). One patient who was treated with sunitinib had frank left ventricular systolic dysfunction. Seven of the eight patients with elevated NT-BNP values had baseline hypertension, and five patients had significant increases in blood pressure during TKI treatment. In all patients with follow-up biomarkers, NT-BNP levels fell after initiation of heart failure therapy. TKI treatment appeared to ‘unmask’ previously subclinical cardiac injury, including prior silent myocardial infarction (one patient), left ventricular hypertrophy (four patients), and valvular disease (three patients). Updated data from the ongoing screening protocol will be presented. Conclusions: The Stanford TKI screening protocol identified a high rate of subclinical cardiotoxicity and allowed for early initiation of heart failure therapy. Further studies are needed to determine if this approach can decrease cardiac morbidity and improve oncologic outcomes by preventing discontinuation or dose interruption of TKI therapy. [Table: see text]

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Left Ventricular Intracavitary Mass and Pericarditis Secondary to Metastatic Renal Cell Carcinoma

Angiology ◽

10.1177/000331970305400416 ◽

2003 ◽

Vol 54 (4) ◽

pp. 495-498 ◽

Cited By ~ 16

Author(s):

Arshad M. Safi ◽

Maurice Rachko ◽

Sharon Sadeghinia ◽

Amadeldin Zineldin ◽

Jinwen Dong ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Metastatic Renal Cell Carcinoma ◽

Renal Cell ◽

Left Ventricular

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95 SEQUENTIAL USE OF TEMSIROLIMUS (TEM) IN PATIENTS WITH METASTATIC RENAL CELL CARCINOMA (MRCC): SAFETY AND EFFICACY FOLLOWING FAILURE OF RECEPTOR TYROSINE KINASE INHIBITOR (TKI) TREATMENT

European Urology Supplements ◽

10.1016/s1569-9056(10)60101-7 ◽

2010 ◽

Vol 9 (2) ◽

pp. 63 ◽

Cited By ~ 3

Author(s):

S. Weikert ◽

C. Kempkensteffen ◽

K. Zimmermann ◽

V. Grünwald ◽

A. Floercken ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Tyrosine Kinase ◽

Tyrosine Kinase Inhibitor ◽

Cell Carcinoma ◽

Metastatic Renal Cell Carcinoma ◽

Receptor Tyrosine Kinase ◽

Renal Cell ◽

Kinase Inhibitor ◽

Safety And Efficacy ◽

Tki Treatment

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Cardiac involvement in patients with sorafenib or sunitinib treatment for metastatic renal cell carcinoma

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.5110 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 5110-5110 ◽

Cited By ~ 5

Author(s):

M. Schmidinger ◽

U. M. Vogl ◽

C. Schukro ◽

A. Bojic ◽

M. Bojic ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Coronary Artery ◽

Cell Carcinoma ◽

Renal Cell ◽

Biochemical Markers ◽

Myocardial Damage ◽

Coronary Artery Occlusion ◽

Artery Occlusion ◽

Gene Products ◽

Tki Treatment

5110 Background: Tyrosine-kinase inhibitors (TKI) of the VEGF and PDGF-receptor have significant clinical activity in patients with renal cell carcinoma (RCC). These agents target the VHL-hypoxia-inducible gene pathway and lead to inhibition of hypoxia- inducible factor (HIF)-induced gene products. Physiologically, HIF-1 related gene products are important mediators of myocardial response to ischemia, myocardial remodeling, peri-infarct vascularisation and vascular permeability. The aim of this prospective observational study was to investigate clinical and biochemical signs of myocardial damage in patients undergoing TKI-treatment for RCC. Methods: 73 consecutive patients (median age 65, range 44–68) intended for TKI treatment were analyzed for medical history of coronary artery disease (CAD) and risk-factors. Measurements of biochemical markers of cardiac damage (creatine kinase MB -CK-MB- and cardiac troponin T -cTNT-) and electrocardiogram (ECG) were performed before treatment. In patients developing cardiac symptoms during TKI treatment and/or at occurrence of CK-MB or TNT elevations, changes in ECG were analyzed and patients underwent echocardiography. Results: All patients had normal CK-MB and TNT levels at baseline. 17 patients (23%) developed (week 2–32 of treatment) significant CK-MB elevation, (TNT n=5), with clinical symptoms in 7 patients. No patient had uncontrolled hypertension. Detailed ECG’s comparison before and during treatment revealed significant changes in 10 out of 17 patients, such as ST-segment depression or elevation, T-wave changes and symptomatic AV-conduction disturbance, requiring pacemaker-implantation. 3 patients underwent coronary angiography with one patient showing acute coronary artery occlusion and myocardial infarction. 6 out of 17 patients had abnormal findings on echocardiography, such as reduced left ventricular function Conclusions: TKI-induced HIF-inhibition may be associated with severe myocardial damage. The underlying mechanism may not necessarily be caused by overt coronary artery occlusion. ECG-changes and biochemical markers are the most important indicators in the preclinical stage. Therefore, careful cardiac monitoring during TKI-treatment is strongly recommended. No significant financial relationships to disclose.

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