Cardiac toxicity of sunitinib and sorafenib in patients with metastatic renal cell carcinoma.

Abstract

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.

• Authors: Manuela Schmidinger, Christoph C Zielinski, Ursula M Vogl, Andja Bojic, Marija Bojic, Christoph Schukro, Marquerite Ruhsam, Michael Hejna, Herwig Schmidinger
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 26 Issue 32 Pg. 5204-12 (Nov 10 2008) ISSN: 1527-7755 [Electronic] United States
• PMID: 18838713 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Benzenesulfonates
• Biomarkers
• Indoles
• Phenylurea Compounds
• Protein Kinase Inhibitors
• Pyridines
• Pyrroles
• Niacinamide
• Sorafenib
• Sunitinib

Topics

• Aged
• Aged, 80 and over
• Benzenesulfonates (adverse effects)
• Biomarkers (blood)
• Carcinoma, Renal Cell (drug therapy, enzymology, mortality, pathology)
• Cardiovascular Diseases (chemically induced, diagnosis, mortality, therapy)
• Echocardiography
• Electrocardiography
• Female
• Humans
• Indoles (adverse effects)
• Kaplan-Meier Estimate
• Kidney Neoplasms (drug therapy, enzymology, mortality, pathology)
• Male
• Middle Aged
• Neoplasm Metastasis
• Niacinamide (analogs & derivatives)
• Phenylurea Compounds
• Prospective Studies
• Protein Kinase Inhibitors (adverse effects)
• Pyridines (adverse effects)
• Pyrroles (adverse effects)
• Risk Factors
• Sorafenib
• Sunitinib
• Time Factors
• Treatment Outcome