Cabozantinib-related cardiotoxicity: a prospective analysis in a real-world cohort of metastatic renal cell carcinoma patients

被引:21
作者
Iacovelli, Roberto [1 ,2 ]
Ciccarese, Chiara [1 ,2 ]
Fornarini, Giuseppe [3 ]
Massari, Francesco [4 ]
Bimbatti, Davide [1 ]
Mosillo, Claudia [1 ]
Rebuzzi, Sara Elena [3 ]
Di Nunno, Vincenzo [4 ]
Grassi, Massimiliano [3 ]
Fantinel, Emanuela [1 ]
Ardizzoni, Andrea [4 ]
Tortora, Giampaolo [1 ,2 ]
机构
[1] AOUI, Dept Med Oncol, Verona, Italy
[2] Fdn Policlin Univ Agostino Gemelli IRCCS, Oncol Med, Rome, Italy
[3] IRCCS Azienda Osped Univ San Martino, Ist Nazl Ric Canc, Dept Med Oncol, Genoa, Italy
[4] St Orsola Malpighi Hosp, Dept Med Oncol, Bologna, Italy
关键词
cabozantinib; cardiotoxicity; high-sensitivity troponin I; metastatic renal cell carcinoma; precursor brain natriuretic peptide; CARDIOVASCULAR TOXICITY; HEART-FAILURE; CONCISE GUIDE; SUNITINIB; THERAPY; RISK;
D O I
10.1111/bcp.13895
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Aims Data regarding the cardiac toxicity of cabozantinib lacks. The aim of our study was to assess the risk of cabozantinib-related cardiotoxicity in mRCC patients. Methods We performed a multicentre prospective study on mRCC patients treated with cabozantinib between October 2016 and November 2017. Transthoracic echocardiogram and plasma biomarkers assay were assessed at baseline, 3 and 6 months after cabozantinib initiation. Results The study population included 22 mRCC patients. At baseline, 9.1% had a reduced left ventricular ejection fraction (LVEF), but none had a left ventricular systolic dysfunction. Patients with baseline reduced LVEF did not show further significant LVEF modification after 3 months. After 6 months, only 1 had an LVEF decline >10% compared to baseline, resulting in LV systolic dysfunction. At baseline, 64.7% and 27.3% of patients had elevated precursor brain natriuretic peptide (proBNP) and high-sensitivity troponin I (hsTnI), respectively. Among patients with basal normal proBNP and hsTnI, none had elevated values at 3 and 6 months. No correlation was found between basal elevated proBNP and basal reduced LVEF (P = .29), and between elevated proBNP and reduced LVEF after 6 months (P = .37). Similarly, we found no correlations between elevated hsTnI and reduced LVEF or elevated proBNP at baseline (P = .47; P = .38), at 3 (P = .059; P = .45) and after 6 months (P = .72; P = 1.0). Conclusions This prospective study revealed a modest risk of developing left ventricular systolic dysfunction related to cabozantinib. A lack of correlation between elevated cardiac biomarkers and reduced LVEF at different time-points was detected. Assessments of the cardiac function should be reserved at the occurrence of clinical symptoms.
引用
收藏
页码:1283 / 1289
页数:7
相关论文
共 22 条
[1]   THE CONCISE GUIDE TO PHARMACOLOGY 2017/18: Overview [J].
Alexander, Stephen P. H. ;
Kelly, Eamonn ;
Marrion, Neil V. ;
Peters, John A. ;
Faccenda, Elena ;
Harding, Simon D. ;
Pawson, Adam J. ;
Sharman, Joanna L. ;
Southan, Christopher ;
Buneman, O. Peter ;
Cidlowski, John A. ;
Christopoulos, Arthur ;
Davenport, Anthony P. ;
Fabbro, Doriano ;
Spedding, Michael ;
Striessnig, Jorg ;
Davies, Jamie A. ;
Abbracchio, M. P. ;
Aldrich, R. ;
Al-Hosaini, K. ;
Arumugam, T., V ;
Attali, B. ;
Back, M. ;
Barnes, N. M. ;
Bathgate, R. ;
Beart, P. M. ;
Becirovic, E. ;
Bettler, B. ;
Biel, M. ;
Birdsall, N. J. ;
Blaho, V ;
Boison, D. ;
Brauner-Osborne, H. ;
Broer, S. ;
Bryant, C. ;
Burnstock, G. ;
Calo, G. ;
Catterall, W. A. ;
Ceruti, S. ;
Chan, S. L. ;
Chandy, K. G. ;
Chazot, P. ;
Chiang, N. ;
Chun, J. J. ;
Chung, J. J. ;
Clapham, D. E. ;
Clapp, L. ;
Connor, M. A. ;
Cox, H. M. ;
Davies, P. .
BRITISH JOURNAL OF PHARMACOLOGY, 2017, 174 :S1-S16
[2]  
Alexander SPH, 2017, BRIT J PHARMACOL, V174, pS272, DOI [10.1111/bph.13877, 10.1111/bph.13882]
[3]  
[Anonymous], 2017, ANN ONCOL
[4]   Is Cabozantinib Really Better Than Sunitinib As First-Line Treatment of Metastatic Renal Cell Carcinoma? [J].
Buti, Sebastiano ;
Bersanelli, Melissa .
JOURNAL OF CLINICAL ONCOLOGY, 2017, 35 (16) :1858-+
[5]   Cabozantinib versus everolimus in advanced renal cell carcinoma (METEOR): final results from a randomised, open-label, phase 3 trial [J].
Choueiri, Toni K. ;
Escudier, Bernard ;
Powles, Thomas ;
Tannir, Nizar M. ;
Mainwaring, Paul N. ;
Rini, Brian I. ;
Hammers, Hans J. ;
Donskov, Frede ;
Roth, Bruce J. ;
Peltola, Katriina ;
Lee, Jae Lyun ;
Heng, Daniel Y. C. ;
Schmidinger, Manuela ;
Agarwal, Neeraj ;
Sternberg, Cora N. ;
McDermott, David F. ;
Aftab, Dana T. ;
Hessel, Colin ;
Old, Christian Scheff ;
Schwab, Gisela ;
Hutson, Thomas E. ;
Pal, Sumanta ;
Motzer, Robert J. .
LANCET ONCOLOGY, 2016, 17 (07) :917-927
[6]   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
[7]   Cardiovascular toxicity following sunitinib therapy in metastatic renal cell carcinoma: a multicenter analysis [J].
Di Lorenzo, G. ;
Autorino, R. ;
Bruni, G. ;
Carteni, G. ;
Ricevuto, E. ;
Tudini, M. ;
Ficorella, C. ;
Romano, C. ;
Aieta, M. ;
Giordano, A. ;
Giuliano, M. ;
Gonnella, A. ;
De Nunzio, C. ;
Rizzo, M. ;
Montesarchio, V. ;
Ewer, M. ;
De Placido, S. .
ANNALS OF ONCOLOGY, 2009, 20 (09) :1535-1542
[8]   Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up [J].
Escudier, B. ;
Porta, C. ;
Schmidinger, M. ;
Rioux-Leclercq, N. ;
Bex, A. ;
Khoo, V. ;
Gruenvald, V. ;
Horwich, A. .
ANNALS OF ONCOLOGY, 2016, 27 :v58-v68
[9]   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
[10]   Effects of Adjuvant Sorafenib and Sunitinib on Cardiac Function in Renal Cell Carcinoma Patients without Overt Metastases: Results from ASSURE, ECOG 2805 [J].
Haas, Naomi B. ;
Manola, Judith ;
Ky, Bonnie ;
Flaherty, Keith T. ;
Uzzo, Robert G. ;
Kane, Christopher J. ;
Jewett, Michael ;
Wood, Lori ;
Wood, Christopher G. ;
Atkins, Michael B. ;
Dutcher, Janice J. ;
Wilding, George ;
DiPaola, Robert S. .
CLINICAL CANCER RESEARCH, 2015, 21 (18) :4048-4054