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Published in: Journal of Cancer Research and Clinical Oncology 9/2008

Open Access 01-09-2008 | Original Paper

Evaluation of biomarkers for cardiotoxicity of anthracyclin-based chemotherapy

Authors: F. J. F. Broeyer, S. Osanto, H. J. Ritsema van Eck, A. Q. M. J. van Steijn, B. E. P. B. Ballieux, R. C. Schoemaker, A. F. Cohen, J. Burggraaf

Published in: Journal of Cancer Research and Clinical Oncology | Issue 9/2008

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Abstract

Introduction

The clinical assessment of the myocardial damage caused by anthracyclin (ANT)-therapy is difficult. Therefore a study was performed to evaluate non-invasive markers of anthracyclin-induced cardiac effects, with emphasis on course-to-course variation.

Methods

Eligible for study participation were patients, without known cardiologic abnormalities who did not use cardiotoxic medication (except for ANT-therapy), who had previously completed at least three cycles of anthracyclin-containing chemotherapy (n = 14) and patients who were ANT-naïve and who were scheduled to receive doxorubicin-containing chemotherapy (n = 12). Seven patients in this last group also completed at least three cycles and were available for follow-up assessments; thus a total population of 21 patients (12F/9M) completed at least three courses ANT-chemotherapy. In these patients blood samples and ECG-recordings were taken within 6 months after completion of ANT-therapy. In 12 patients (10F/2M) assessments were also done before, immediately afterwards and at 24 h after each course of ANT.

Results and Conclusions

In the patients who completed chemotherapy, NT-proBNP was 277% (n = 21; 95% CI: 86–661%, P < 0.001) higher compared to healthy volunteers. During the first course NT-proBNP rose 269% (n = 12; 167–409%, P < 0.0001) at 24 h post-administration. The linear corrected QT (QTcL) directly after the first administration of ANT increased by 9.56 ms (n = 12; 3.85–15.27, P < 0.001) and this prolongation was still present at 24 h, 11.48 ms (n = 12; 5.61–17.34, P < 0.0001). Both NT-proBNP and QTcL returned to baseline before the start of the next course and a similar pattern was observed during each course. NT-proBNP and QTcL may be useful markers for course-to-course evaluation of anthracyclin-induced cardiotoxicity.
Literature
go back to reference Arola OJ, Saraste A, Pulkki K, Kallajoki M, Parvinen M, Voipio-Pulkki LM (2000) Acute doxorubicin cardiotoxicity involves cardiomyocyte apoptosis. Cancer Res 60:1789–1792PubMed Arola OJ, Saraste A, Pulkki K, Kallajoki M, Parvinen M, Voipio-Pulkki LM (2000) Acute doxorubicin cardiotoxicity involves cardiomyocyte apoptosis. Cancer Res 60:1789–1792PubMed
go back to reference Bennink RJ, van den Hoff MJ, van Hemert FJ, de Bruin KM, Spijkerboer AL, Vanderheyden JL, Steinmetz N, Eck-Smit BL (2004) Annexin V imaging of acute doxorubicin cardiotoxicity (apoptosis) in rats. J Nucl Med 45:842–848PubMed Bennink RJ, van den Hoff MJ, van Hemert FJ, de Bruin KM, Spijkerboer AL, Vanderheyden JL, Steinmetz N, Eck-Smit BL (2004) Annexin V imaging of acute doxorubicin cardiotoxicity (apoptosis) in rats. J Nucl Med 45:842–848PubMed
go back to reference Brooksby P, Batin PD, Nolan J, Lindsay SJ, Andrews R, Mullen M, Baig W, Flapan AD, Prescott RJ, Neilson JM, Cowley AJ, Fox KA (1999) The relationship between QT intervals and mortality in ambulant patients with chronic heart failure. The United Kingdom heart failure evaluation and assessment of risk trial (UK-HEART). Eur Heart J 20:1335–1341PubMedCrossRef Brooksby P, Batin PD, Nolan J, Lindsay SJ, Andrews R, Mullen M, Baig W, Flapan AD, Prescott RJ, Neilson JM, Cowley AJ, Fox KA (1999) The relationship between QT intervals and mortality in ambulant patients with chronic heart failure. The United Kingdom heart failure evaluation and assessment of risk trial (UK-HEART). Eur Heart J 20:1335–1341PubMedCrossRef
go back to reference Cardinale D, Sandri MT, Colombo A, Colombo N, Boeri M, Lamantia G, Civelli M, Peccatori F, Martinelli G, Fiorentini C, Cipolla CM (2004) Prognostic value of troponin I in cardiac risk stratification of cancer patients undergoing high-dose chemotherapy. Circulation 109:2749–2754PubMedCrossRef Cardinale D, Sandri MT, Colombo A, Colombo N, Boeri M, Lamantia G, Civelli M, Peccatori F, Martinelli G, Fiorentini C, Cipolla CM (2004) Prognostic value of troponin I in cardiac risk stratification of cancer patients undergoing high-dose chemotherapy. Circulation 109:2749–2754PubMedCrossRef
go back to reference Charbit B, Albaladejo P, Funck-Brentano C, Legrand M, Samain E, Marty J (2005) Prolongation of QTc interval after postoperative nausea and vomiting treatment by droperidol or ondansetron. Anesthesiology 102:1094–1100PubMedCrossRef Charbit B, Albaladejo P, Funck-Brentano C, Legrand M, Samain E, Marty J (2005) Prolongation of QTc interval after postoperative nausea and vomiting treatment by droperidol or ondansetron. Anesthesiology 102:1094–1100PubMedCrossRef
go back to reference Daugaard G, Lassen U, Bie P, Pedersen EB, Jensen KT, Abildgaard U, Hesse B, Kjaer A (2005) Natriuretic peptides in the monitoring of anthracycline induced reduction in left ventricular ejection fraction. Eur J Heart Fail 7:87–93PubMedCrossRef Daugaard G, Lassen U, Bie P, Pedersen EB, Jensen KT, Abildgaard U, Hesse B, Kjaer A (2005) Natriuretic peptides in the monitoring of anthracycline induced reduction in left ventricular ejection fraction. Eur J Heart Fail 7:87–93PubMedCrossRef
go back to reference Ewer MS, Benjamin RS (1996) Cardiotoxicity of chemotherapeutic drugs. In: Perry MC (ed). Baltimore, pp 649–663 Ewer MS, Benjamin RS (1996) Cardiotoxicity of chemotherapeutic drugs. In: Perry MC (ed). Baltimore, pp 649–663
go back to reference Fink FM, Genser N, Fink C, Falk M, Mair J, Maurer-Dengg K, Hammerer I, Puschendorf B (1995) Cardiac troponin T and creatine kinase MB mass concentrations in children receiving anthracycline chemotherapy. Med Pediatr Oncol 25:185–189PubMedCrossRef Fink FM, Genser N, Fink C, Falk M, Mair J, Maurer-Dengg K, Hammerer I, Puschendorf B (1995) Cardiac troponin T and creatine kinase MB mass concentrations in children receiving anthracycline chemotherapy. Med Pediatr Oncol 25:185–189PubMedCrossRef
go back to reference Kilickap S, Barista I, Akgul E, Aytemir K, Aksoyek S, Aksoy S, Celik I, Kes S, Tekuzman G (2005) cTnT can be a useful marker for early detection of anthracycline cardiotoxicity. Ann Oncol 16:798–804PubMedCrossRef Kilickap S, Barista I, Akgul E, Aytemir K, Aksoyek S, Aksoy S, Celik I, Kes S, Tekuzman G (2005) cTnT can be a useful marker for early detection of anthracycline cardiotoxicity. Ann Oncol 16:798–804PubMedCrossRef
go back to reference Kismet E, Varan A, Ayabakan C, Alehan D, Portakal O, Buyukpamukcu M (2004) Serum troponin T levels and echocardiographic evaluation in children treated with doxorubicin. Pediatr Blood Cancer 42:220–224PubMedCrossRef Kismet E, Varan A, Ayabakan C, Alehan D, Portakal O, Buyukpamukcu M (2004) Serum troponin T levels and echocardiographic evaluation in children treated with doxorubicin. Pediatr Blood Cancer 42:220–224PubMedCrossRef
go back to reference Kumar D, Kirshenbaum LA, Li T, Danelisen I, Singal PK (2001) Apoptosis in adriamycin cardiomyopathy and its modulation by probucol. Antioxid Redox Signal 3:135–145PubMedCrossRef Kumar D, Kirshenbaum LA, Li T, Danelisen I, Singal PK (2001) Apoptosis in adriamycin cardiomyopathy and its modulation by probucol. Antioxid Redox Signal 3:135–145PubMedCrossRef
go back to reference Launchbury AP, Habboubi N (1993) Epirubicin and doxorubicin: a comparison of their characteristics, therapeutic activity and toxicity. Cancer Treat Rev 19:197–228PubMedCrossRef Launchbury AP, Habboubi N (1993) Epirubicin and doxorubicin: a comparison of their characteristics, therapeutic activity and toxicity. Cancer Treat Rev 19:197–228PubMedCrossRef
go back to reference Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D (1999) A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of diet in renal disease study group. Ann Intern Med 130:461–470PubMed Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D (1999) A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of diet in renal disease study group. Ann Intern Med 130:461–470PubMed
go back to reference Lipshultz SE, Rifai N, Sallan SE, Lipsitz SR, Dalton V, Sacks DB, Ottlinger ME (1997) Predictive Value of Cardiac Troponin T in pediatric patients at risk for myocardial injury. Circulation 96:2641–2648PubMed Lipshultz SE, Rifai N, Sallan SE, Lipsitz SR, Dalton V, Sacks DB, Ottlinger ME (1997) Predictive Value of Cardiac Troponin T in pediatric patients at risk for myocardial injury. Circulation 96:2641–2648PubMed
go back to reference Luchner A, Hengstenberg C, Lowel H, Riegger GA, Schunkert H, Holmer S (2005) Effect of compensated renal dysfunction on approved heart failure markers: direct comparison of brain natriuretic peptide (BNP) and N-terminal pro-BNP. Hypertension 46:118–123PubMedCrossRef Luchner A, Hengstenberg C, Lowel H, Riegger GA, Schunkert H, Holmer S (2005) Effect of compensated renal dysfunction on approved heart failure markers: direct comparison of brain natriuretic peptide (BNP) and N-terminal pro-BNP. Hypertension 46:118–123PubMedCrossRef
go back to reference Malasky BR, Alpert JS (2002) Diagnosis of myocardial injury by biochemical markers: problems and promises. Cardiol Rev 10:306–317PubMedCrossRef Malasky BR, Alpert JS (2002) Diagnosis of myocardial injury by biochemical markers: problems and promises. Cardiol Rev 10:306–317PubMedCrossRef
go back to reference Masson S, Latini R, Anand IS, Vago T, Angelici L, Barlera S, Missov ED, Clerico A, Tognoni G, Cohn JN (2006) Direct comparison of B-type natriuretic peptide (BNP) and amino-terminal proBNP in a large population of patients with chronic and symptomatic heart failure: the Valsartan heart failure (Val-HeFT) data. Clin Chem 52:1528–1538PubMedCrossRef Masson S, Latini R, Anand IS, Vago T, Angelici L, Barlera S, Missov ED, Clerico A, Tognoni G, Cohn JN (2006) Direct comparison of B-type natriuretic peptide (BNP) and amino-terminal proBNP in a large population of patients with chronic and symptomatic heart failure: the Valsartan heart failure (Val-HeFT) data. Clin Chem 52:1528–1538PubMedCrossRef
go back to reference Meinardi MT, van Veldhuisen DJ, Gietema JA, Dolsma WV, Boomsma F, van den Berg MP, Volkers C, Haaksma J, de Vries EG, Sleijfer DT, van der Graaf WT (2001) Prospective evaluation of early cardiac damage induced by epirubicin-containing adjuvant chemotherapy and locoregional radiotherapy in breast cancer patients. J Clin Oncol 19:2746–2753PubMed Meinardi MT, van Veldhuisen DJ, Gietema JA, Dolsma WV, Boomsma F, van den Berg MP, Volkers C, Haaksma J, de Vries EG, Sleijfer DT, van der Graaf WT (2001) Prospective evaluation of early cardiac damage induced by epirubicin-containing adjuvant chemotherapy and locoregional radiotherapy in breast cancer patients. J Clin Oncol 19:2746–2753PubMed
go back to reference Minotti G, Menna P, Salvatorelli E, Cairo G, Gianni L (2004) Anthracyclines: molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacol Rev 56:185–229PubMedCrossRef Minotti G, Menna P, Salvatorelli E, Cairo G, Gianni L (2004) Anthracyclines: molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacol Rev 56:185–229PubMedCrossRef
go back to reference Missov E, Calzolari C, Davy JM, Leclercq F, Rossi M, Pau B (1997) Cardiac troponin I in patients with hematologic malignancies. Coron Artery Dis 8:537–541PubMed Missov E, Calzolari C, Davy JM, Leclercq F, Rossi M, Pau B (1997) Cardiac troponin I in patients with hematologic malignancies. Coron Artery Dis 8:537–541PubMed
go back to reference Ritsema van Eck HJ (2002) Fiducial segment averaging to improve cardiac time interval estimates. J Electrocardiol 35:89–93CrossRef Ritsema van Eck HJ (2002) Fiducial segment averaging to improve cardiac time interval estimates. J Electrocardiol 35:89–93CrossRef
go back to reference Shan K, Lincoff AM, Young JB (1996) Anthracycline-induced cardiotoxicity. Ann Intern Med 125:47–58PubMed Shan K, Lincoff AM, Young JB (1996) Anthracycline-induced cardiotoxicity. Ann Intern Med 125:47–58PubMed
go back to reference Silver MA, Maisel A, Yancy CW, McCullough PA, Burnett JC Jr, Francis GS, Mehra MR, Peacock WF, Fonarow G, Gibler WB, Morrow DA, Hollander J (2004) BNP consensus panel 2004: a clinical approach for the diagnostic, prognostic, screening, treatment monitoring, and therapeutic roles of natriuretic peptides in cardiovascular diseases. Congest Heart Fail 10:1–30CrossRef Silver MA, Maisel A, Yancy CW, McCullough PA, Burnett JC Jr, Francis GS, Mehra MR, Peacock WF, Fonarow G, Gibler WB, Morrow DA, Hollander J (2004) BNP consensus panel 2004: a clinical approach for the diagnostic, prognostic, screening, treatment monitoring, and therapeutic roles of natriuretic peptides in cardiovascular diseases. Congest Heart Fail 10:1–30CrossRef
go back to reference Singal PK, Iliskovic N, Li T, Kumar D (1997) Adriamycin cardiomyopathy: pathophysiology and prevention. FASEB J 11:931–936PubMed Singal PK, Iliskovic N, Li T, Kumar D (1997) Adriamycin cardiomyopathy: pathophysiology and prevention. FASEB J 11:931–936PubMed
go back to reference Suzuki T, Hayashi D, Yamazaki T, Mizuno T, Kanda Y, Komuro I, Kurabayashi M, Yamaoki K, Mitani K, Hirai H, Nagai R, Yazaki Y (1998) Elevated B-type natriuretic peptide levels after anthracycline administration. Am Heart J 136:362–363PubMedCrossRef Suzuki T, Hayashi D, Yamazaki T, Mizuno T, Kanda Y, Komuro I, Kurabayashi M, Yamaoki K, Mitani K, Hirai H, Nagai R, Yazaki Y (1998) Elevated B-type natriuretic peptide levels after anthracycline administration. Am Heart J 136:362–363PubMedCrossRef
go back to reference Swain SM, Whaley FS, Ewer MS (2003) Congestive heart failure in patients treated with doxorubicin: a retrospective analysis of three trials. Cancer 97:2869–2879PubMedCrossRef Swain SM, Whaley FS, Ewer MS (2003) Congestive heart failure in patients treated with doxorubicin: a retrospective analysis of three trials. Cancer 97:2869–2879PubMedCrossRef
go back to reference Thorburn A, Frankel AE (2006) Apoptosis and anthracycline cardiotoxicity. Mol Cancer Ther 5:197–199PubMedCrossRef Thorburn A, Frankel AE (2006) Apoptosis and anthracycline cardiotoxicity. Mol Cancer Ther 5:197–199PubMedCrossRef
go back to reference Von Hoff DD, Layard MW, Basa P, Davis HL Jr, Von Hoff AL, Rozencweig M, Muggia FM (1979) Risk factors for doxorubicin-induced congestive heart failure. Ann Intern Med 91:710–717 Von Hoff DD, Layard MW, Basa P, Davis HL Jr, Von Hoff AL, Rozencweig M, Muggia FM (1979) Risk factors for doxorubicin-induced congestive heart failure. Ann Intern Med 91:710–717
go back to reference Weber M, Hamm C (2006) Role of B-type natriuretic peptide (BNP) and NT-proBNP in clinical routine. Heart 92:843–849PubMedCrossRef Weber M, Hamm C (2006) Role of B-type natriuretic peptide (BNP) and NT-proBNP in clinical routine. Heart 92:843–849PubMedCrossRef
go back to reference Wondergem J, Strootman EG, Frolich M, Leer JW, Noordijk EM (2001) Circulating atrial natriuretic peptide plasma levels as a marker for cardiac damage after radiotherapy. Radiother Oncol 58:295–301PubMedCrossRef Wondergem J, Strootman EG, Frolich M, Leer JW, Noordijk EM (2001) Circulating atrial natriuretic peptide plasma levels as a marker for cardiac damage after radiotherapy. Radiother Oncol 58:295–301PubMedCrossRef
Metadata
Title
Evaluation of biomarkers for cardiotoxicity of anthracyclin-based chemotherapy
Authors
F. J. F. Broeyer
S. Osanto
H. J. Ritsema van Eck
A. Q. M. J. van Steijn
B. E. P. B. Ballieux
R. C. Schoemaker
A. F. Cohen
J. Burggraaf
Publication date
01-09-2008
Publisher
Springer-Verlag
Published in
Journal of Cancer Research and Clinical Oncology / Issue 9/2008
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-008-0372-8

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