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


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.


CONCLUSIONS
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.
Clinical Division of Oncology, Department of Medicine I and Cancer Center, Medical University of Vienna, Vienna, Austria. manuela.schmidinger@meduniwien.ac.at
Manuela
M
Schmidinger
Christoph C
CC
Zielinski
Ursula M
UM
Vogl
Andja
A
Bojic
Marija
M
Bojic
Christoph
C
Schukro
Marquerite
M
Ruhsam
Michael
M
Hejna
Herwig
H
Schmidinger
D000368:Aged; D000369:Aged, 80 and over; D001557:Benzenesulfonates / Q000009:adverse effects*; D015415:Biomarkers / Q000097:blood; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000201:enzymology / Q000401:mortality / Q000473:pathology; D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000175:diagnosis / Q000401:mortality / Q000628:therapy; D004452:Echocardiography; D004562:Electrocardiography; D005260:Female; D006801:Humans; D007211:Indoles / Q000009:adverse effects*; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011446:Prospective Studies; D047428:Protein Kinase Inhibitors / Q000009:adverse effects*; D011725:Pyridines / Q000009:adverse effects*; D011758:Pyrroles / Q000009:adverse effects*; D012307:Risk Factors; D000077157:Sorafenib; D000077210:Sunitinib; D013997:Time Factors; D016896:Treatment Outcome
D001557:Benzenesulfonates; D015415:Biomarkers; D007211:Indoles; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D011758:Pyrroles; D009536:Niacinamide; D000077157:Sorafenib; D000077210:Sunitinib