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

被引:471
作者
Schmidinger, Manuela [1 ]
Zielinski, Christoph C.
Vogl, Ursula M.
Bojic, Andja
Bojic, Marija
Schukro, Christoph
Ruhsam, Marquerite
Hejna, Michael
Schmidinger, Herwig
机构
[1] Med Univ Vienna, Dept Med 1, Div Clin Oncol, A-1090 Vienna, Austria
关键词
D O I
10.1200/JCO.2007.15.6331
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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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页码:5204 / 5212
页数:9
相关论文
共 29 条
[1]  
ADLER F H, 1952, Trans Stud Coll Physicians Phila, V19, P121
[2]  
Bassand JP, 2007, EUR HEART J, V28, P1598, DOI 10.1093/eurheartj/ehm161
[3]   Raf: A strategic target for therapeutic development against cancer [J].
Beeram, M ;
Patnaik, A ;
Rowinsky, EK .
JOURNAL OF CLINICAL ONCOLOGY, 2005, 23 (27) :6771-6790
[4]   Renal-cell carcinoma - Molecular pathways and therapies [J].
Brugarolas, James .
NEW ENGLAND JOURNAL OF MEDICINE, 2007, 356 (02) :185-187
[5]   Prognostic value of troponin I in cardiac risk stratification of cancer patients undergoing high-dose chemotherapy [J].
Cardinale, D ;
Sandri, MT ;
Colombo, A ;
Colombo, N ;
Boeri, M ;
Lamantia, G ;
Civelli, M ;
Peccatori, F ;
Martinelli, G ;
Fiorentini, C ;
Cipolla, CM .
CIRCULATION, 2004, 109 (22) :2749-2754
[6]  
Carreira R. S., 2006, Cardiovascular & Hematological Disorders - Drug Targets, V6, P257
[7]   Cardiotoxicity associated with tyrosine kinase inhibitor sunitinib [J].
Chu, Tammy F. ;
Rupnick, Maria A. ;
Kerkela, Risto ;
Dallabrida, Susan M. ;
Zurakowski, David ;
Nguyen, Lisa ;
Woulfe, Kathleen ;
Pravda, Elke ;
Cassiola, Flavia ;
Desai, Jayesh ;
George, Suzanne ;
Morgan, Jeffrey A. ;
Harris, David M. ;
Ismail, Nesreen S. ;
Chen, Jey-Hsin ;
Schoen, Frederick J. ;
Van den Abbeele, Annick D. ;
Demetri, George D. ;
Force, Thomas ;
Chen, Ming Hui .
LANCET, 2007, 370 (9604) :2011-2019
[8]   Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial [J].
Demetri, George D. ;
van Oosterom, Allan T. ;
Garrett, Christopher R. ;
Blackstein, Martin E. ;
Shah, Manisha H. ;
Verweij, Jaap ;
McArthur, Grant ;
Judson, Ian R. ;
Heinrich, Michael C. ;
Morgan, Jeffrey A. ;
Desai, Jayesh ;
D Fletcher, Christopher ;
George, Suzanne ;
Bello, Carlo L. ;
Huang, Xin ;
Baum, Charles M. ;
Casali, Paolo G. .
LANCET, 2006, 368 (9544) :1329-1338
[9]   Sorafenib in advanced clear-cell renal-cell carcinoma [J].
Escudier, Bernard ;
Eisen, Tim ;
Stadler, Walter M. ;
Szczylik, Cezary ;
Oudard, Stephane ;
Siebels, Michael ;
Negrier, Sylvie ;
Chevreau, Christine ;
Solska, Ewa ;
Desai, Apurva A. ;
Rolland, Frederic ;
Demkow, Tomasz ;
Hutson, Thomas E. ;
Gore, Martin ;
Freeman, Scott ;
Schwartz, Brian ;
Shan, Minghua ;
Simantov, Ronit ;
Bukowski, Ronald M. .
NEW ENGLAND JOURNAL OF MEDICINE, 2007, 356 (02) :125-134
[10]   Molecular mechanisms of cardiotoxicity of tyrosine kinase inhibition [J].
Force, Thomas ;
Krause, Daniela S. ;
Van Etten, Richard A. .
NATURE REVIEWS CANCER, 2007, 7 (05) :332-344