Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate®

Cardiotoxicity of anthracycline-like chemotherapy agents

Justin Floyd, DO
James P Morgan, MD, PhD
Stacey Berg, MD
Section Editors
Reed E Drews, MD
David G Poplack, MD
Stephen S Gottlieb, MD
Deputy Editor
Sadhna R Vora, MD


Cancer patients who are undergoing chemotherapy have an increased risk of developing cardiovascular complications, and the risk is even greater if there is a known history of heart disease. Among the serious clinical cardiac complications that have been reported are:


Myocardial necrosis causing a dilated cardiomyopathy

Vasoocclusion or vasospasm resulting in angina or myocardial infarction

A wide range of chemotherapy agents have been associated with cardiotoxicity [1,2]. The anthracyclines and related compounds (doxorubicin, daunorubicin, idarubicin, epirubicin, and the anthraquinone mitoxantrone) are some of the most frequently implicated agents [3].


Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Jan 2017. | This topic last updated: Wed Dec 02 00:00:00 GMT 2015.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Floyd JD, Nguyen DT, Lobins RL, et al. Cardiotoxicity of cancer therapy. J Clin Oncol 2005; 23:7685.
  2. Monsuez JJ, Charniot JC, Vignat N, Artigou JY. Cardiac side-effects of cancer chemotherapy. Int J Cardiol 2010; 144:3.
  3. Singal PK, Iliskovic N. Doxorubicin-induced cardiomyopathy. N Engl J Med 1998; 339:900.
  4. Isner JM, Ferrans VJ, Cohen SR, et al. Clinical and morphologic cardiac findings after anthracycline chemotherapy. Analysis of 64 patients studied at necropsy. Am J Cardiol 1983; 51:1167.
  5. Nakamae H, Tsumura K, Terada Y, et al. Notable effects of angiotensin II receptor blocker, valsartan, on acute cardiotoxic changes after standard chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisolone. Cancer 2005; 104:2492.
  6. Guglin M, Aljayeh M, Saiyad S, et al. Introducing a new entity: chemotherapy-induced arrhythmia. Europace 2009; 11:1579.
  7. Shan K, Lincoff AM, Young JB. Anthracycline-induced cardiotoxicity. Ann Intern Med 1996; 125:47.
  8. Barrett-Lee PJ, Dixon JM, Farrell C, et al. Expert opinion on the use of anthracyclines in patients with advanced breast cancer at cardiac risk. Ann Oncol 2009; 20:816.
  9. Wojnowski L, Kulle B, Schirmer M, et al. NAD(P)H oxidase and multidrug resistance protein genetic polymorphisms are associated with doxorubicin-induced cardiotoxicity. Circulation 2005; 112:3754.
  10. Doroshow JH. Doxorubicin-induced cardiac toxicity. N Engl J Med 1991; 324:843.
  11. Steinberg JS, Cohen AJ, Wasserman AG, et al. Acute arrhythmogenicity of doxorubicin administration. Cancer 1987; 60:1213.
  12. Rudzinski T, Ciesielczyk M, Religa W, et al. Doxorubicin-induced ventricular arrhythmia treated by implantation of an automatic cardioverter-defibrillator. Europace 2007; 9:278.
  13. Kilickap S, Akgul E, Aksoy S, et al. Doxorubicin-induced second degree and complete atrioventricular block. Europace 2005; 7:227.
  14. Luminari S, Montanini A, Caballero D, et al. Nonpegylated liposomal doxorubicin (MyocetTM) combination (R-COMP) chemotherapy in elderly patients with diffuse large B-cell lymphoma (DLBCL): results from the phase II EUR018 trial. Ann Oncol 2010; 21:1492.
  15. Tirelli U, Errante D, Van Glabbeke M, et al. CHOP is the standard regimen in patients > or = 70 years of age with intermediate-grade and high-grade non-Hodgkin's lymphoma: results of a randomized study of the European Organization for Research and Treatment of Cancer Lymphoma Cooperative Study Group. J Clin Oncol 1998; 16:27.
  16. Cardinale D, Sandri MT, Martinoni A, et al. Left ventricular dysfunction predicted by early troponin I release after high-dose chemotherapy. J Am Coll Cardiol 2000; 36:517.
  17. Smith LA, Cornelius VR, Plummer CJ, et al. Cardiotoxicity of anthracycline agents for the treatment of cancer: systematic review and meta-analysis of randomised controlled trials. BMC Cancer 2010; 10:337.
  18. Von Hoff DD, Rozencweig M, Layard M, et al. Daunomycin-induced cardiotoxicity in children and adults. A review of 110 cases. Am J Med 1977; 62:200.
  19. Von Hoff DD, Layard MW, Basa P, et al. Risk factors for doxorubicin-induced congestive heart failure. Ann Intern Med 1979; 91:710.
  20. Lipshultz SE, Colan SD, Gelber RD, et al. Late cardiac effects of doxorubicin therapy for acute lymphoblastic leukemia in childhood. N Engl J Med 1991; 324:808.
  21. van der Pal HJ, van Dalen EC, Hauptmann M, et al. Cardiac function in 5-year survivors of childhood cancer: a long-term follow-up study. Arch Intern Med 2010; 170:1247.
  22. Singal PK, Deally CM, Weinberg LE. Subcellular effects of adriamycin in the heart: a concise review. J Mol Cell Cardiol 1987; 19:817.
  23. Adderley SR, Fitzgerald DJ. Oxidative damage of cardiomyocytes is limited by extracellular regulated kinases 1/2-mediated induction of cyclooxygenase-2. J Biol Chem 1999; 274:5038.
  24. Dowd NP, Scully M, Adderley SR, et al. Inhibition of cyclooxygenase-2 aggravates doxorubicin-mediated cardiac injury in vivo. J Clin Invest 2001; 108:585.
  25. Singal PK, Iliskovic N, Li T, Kumar D. Adriamycin cardiomyopathy: pathophysiology and prevention. FASEB J 1997; 11:931.
  26. Li T, Singal PK. Adriamycin-induced early changes in myocardial antioxidant enzymes and their modulation by probucol. Circulation 2000; 102:2105.
  27. Martin E, Thougaard AV, Grauslund M, et al. Evaluation of the topoisomerase II-inactive bisdioxopiperazine ICRF-161 as a protectant against doxorubicin-induced cardiomyopathy. Toxicology 2009; 255:72.
  28. Tewey KM, Rowe TC, Yang L, et al. Adriamycin-induced DNA damage mediated by mammalian DNA topoisomerase II. Science 1984; 226:466.
  29. Lyu YL, Lin CP, Azarova AM, et al. Role of topoisomerase IIbeta in the expression of developmentally regulated genes. Mol Cell Biol 2006; 26:7929.
  30. Capranico G, Tinelli S, Austin CA, et al. Different patterns of gene expression of topoisomerase II isoforms in differentiated tissues during murine development. Biochim Biophys Acta 1992; 1132:43.
  31. Lyu YL, Kerrigan JE, Lin CP, et al. Topoisomerase IIbeta mediated DNA double-strand breaks: implications in doxorubicin cardiotoxicity and prevention by dexrazoxane. Cancer Res 2007; 67:8839.
  32. Zhang S, Liu X, Bawa-Khalfe T, et al. Identification of the molecular basis of doxorubicin-induced cardiotoxicity. Nat Med 2012; 18:1639.
  33. Hershman DL, McBride RB, Eisenberger A, et al. Doxorubicin, cardiac risk factors, and cardiac toxicity in elderly patients with diffuse B-cell non-Hodgkin's lymphoma. J Clin Oncol 2008; 26:3159.
  34. Carver JR, Shapiro CL, Ng A, et al. American Society of Clinical Oncology clinical evidence review on the ongoing care of adult cancer survivors: cardiac and pulmonary late effects. J Clin Oncol 2007; 25:3991.
  35. Bristow MR, Mason JW, Billingham ME, Daniels JR. Dose-effect and structure-function relationships in doxorubicin cardiomyopathy. Am Heart J 1981; 102:709.
  36. Swain SM, Whaley FS, Ewer MS. Congestive heart failure in patients treated with doxorubicin: a retrospective analysis of three trials. Cancer 2003; 97:2869.
  37. Blanco J, Sun C, Landier W, et al. Anthracycline-related cardiomyopathy in childhood cancer survivors and association with polymorphisms in the carbonyl reductase genes: A Children's Oncology Group study (abstract 9512). J Clin Oncol 2010; 28:681s.
  38. Shapiro CL, Hardenbergh PH, Gelman R, et al. Cardiac effects of adjuvant doxorubicin and radiation therapy in breast cancer patients. J Clin Oncol 1998; 16:3493.
  39. Armenian SH, Sun CL, Francisco L, et al. Late congestive heart failure after hematopoietic cell transplantation. J Clin Oncol 2008; 26:5537.
  40. Wang X, Liu W, Sun CL, et al. Hyaluronan synthase 3 variant and anthracycline-related cardiomyopathy: a report from the children's oncology group. J Clin Oncol 2014; 32:647.
  41. Casper ES, Gaynor JJ, Hajdu SI, et al. A prospective randomized trial of adjuvant chemotherapy with bolus versus continuous infusion of doxorubicin in patients with high-grade extremity soft tissue sarcoma and an analysis of prognostic factors. Cancer 1991; 68:1221.
  42. Shapira J, Gotfried M, Lishner M, Ravid M. Reduced cardiotoxicity of doxorubicin by a 6-hour infusion regimen. A prospective randomized evaluation. Cancer 1990; 65:870.
  43. Zalupski M, Metch B, Balcerzak S, et al. Phase III comparison of doxorubicin and dacarbazine given by bolus versus infusion in patients with soft-tissue sarcomas: a Southwest Oncology Group study. J Natl Cancer Inst 1991; 83:926.
  44. van Dalen EC, van der Pal HJ, Caron HN, Kremer LC. Different dosage schedules for reducing cardiotoxicity in cancer patients receiving anthracycline chemotherapy. Cochrane Database Syst Rev 2006; :CD005008.
  45. Legha SS, Benjamin RS, Mackay B, et al. Reduction of doxorubicin cardiotoxicity by prolonged continuous intravenous infusion. Ann Intern Med 1982; 96:133.
  46. Speyer JL, Green MD, Dubin N, et al. Prospective evaluation of cardiotoxicity during a six-hour doxorubicin infusion regimen in women with adenocarcinoma of the breast. Am J Med 1985; 78:555.
  47. Ryberg M, Nielsen D, Skovsgaard T, et al. Epirubicin cardiotoxicity: an analysis of 469 patients with metastatic breast cancer. J Clin Oncol 1998; 16:3502.
  48. Neidhart JA, Gochnour D, Roach R, et al. A comparison of mitoxantrone and doxorubicin in breast cancer. J Clin Oncol 1986; 4:672.
  49. Henderson IC, Allegra JC, Woodcock T, et al. Randomized clinical trial comparing mitoxantrone with doxorubicin in previously treated patients with metastatic breast cancer. J Clin Oncol 1989; 7:560.
  50. Bennett JM, Muss HB, Doroshow JH, et al. A randomized multicenter trial comparing mitoxantrone, cyclophosphamide, and fluorouracil with doxorubicin, cyclophosphamide, and fluorouracil in the therapy of metastatic breast carcinoma. J Clin Oncol 1988; 6:1611.
  51. Kaklamani VG, Gradishar WJ. Epirubicin versus doxorubicin: which is the anthracycline of choice for the treatment of breast cancer? Clin Breast Cancer 2003; 4 Suppl 1:S26.
  52. Minotti G, Menna P, Salvatorelli E, et al. Anthracyclines: molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacol Rev 2004; 56:185.
  53. Nair R, Ramakrishnan G, Nair NN, et al. A randomized comparison of the efficacy and toxicity of epirubicin and doxorubicin in the treatment of patients with non-Hodgkin's lymphoma. Cancer 1998; 82:2282.
  54. Ryberg M, Nielsen D, Cortese G, et al. New insight into epirubicin cardiac toxicity: competing risks analysis of 1097 breast cancer patients. J Natl Cancer Inst 2008; 100:1058.
  55. Saletan S. Mitoxantrone: an active, new antitumor agent with an improved therapeutic index. Cancer Treat Rev 1987; 14:297.
  56. Posner LE, Dukart G, Goldberg J, et al. Mitoxantrone: an overview of safety and toxicity. Invest New Drugs 1985; 3:123.
  57. Schell FC, Yap HY, Blumenschein G, et al. Potential cardiotoxicity with mitoxantrone. Cancer Treat Rep 1982; 66:1641.
  58. Young AM, Dhillon T, Bower M. Cardiotoxicity after liposomal anthracyclines. Lancet Oncol 2004; 5:654.
  59. Gabizon AA, Lyass O, Berry GJ, Wildgust M. Cardiac safety of pegylated liposomal doxorubicin (Doxil/Caelyx) demonstrated by endomyocardial biopsy in patients with advanced malignancies. Cancer Invest 2004; 22:663.
  60. Andreopoulou E, Gaiotti D, Kim E, et al. Pegylated liposomal doxorubicin HCL (PLD; Caelyx/Doxil): experience with long-term maintenance in responding patients with recurrent epithelial ovarian cancer. Ann Oncol 2007; 18:716.
  61. Yildirim Y, Gultekin E, Avci ME, et al. Cardiac safety profile of pegylated liposomal doxorubicin reaching or exceeding lifetime cumulative doses of 550 mg/m2 in patients with recurrent ovarian and peritoneal cancer. Int J Gynecol Cancer 2008; 18:223.
  62. Berry G, Billingham M, Alderman E, et al. The use of cardiac biopsy to demonstrate reduced cardiotoxicity in AIDS Kaposi's sarcoma patients treated with pegylated liposomal doxorubicin. Ann Oncol 1998; 9:711.
  63. Safra T, Muggia F, Jeffers S, et al. Pegylated liposomal doxorubicin (doxil): reduced clinical cardiotoxicity in patients reaching or exceeding cumulative doses of 500 mg/m2. Ann Oncol 2000; 11:1029.
  64. Gill SE, Savage K, Wysham WZ, et al. Continuing routine cardiac surveillance in long-term use of pegylated liposomal doxorubicin: is it necessary? Gynecol Oncol 2013; 129:544.
  65. http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=21d9c619-7e94-49e2-ac41-31e9ea96554a#nlm34068-7 (Accessed on May 16, 2013).
  66. Seifert CF, Nesser ME, Thompson DF. Dexrazoxane in the prevention of doxorubicin-induced cardiotoxicity. Ann Pharmacother 1994; 28:1063.
  67. Deng S, Yan T, Nikolova T, et al. The catalytic topoisomerase II inhibitor dexrazoxane induces DNA breaks, ATF3 and the DNA damage response in cancer cells. Br J Pharmacol 2015; 172:2246.
  68. Popelová O, Sterba M, Hasková P, et al. Dexrazoxane-afforded protection against chronic anthracycline cardiotoxicity in vivo: effective rescue of cardiomyocytes from apoptotic cell death. Br J Cancer 2009; 101:792.
  69. Hensley ML, Hagerty KL, Kewalramani T, et al. American Society of Clinical Oncology 2008 clinical practice guideline update: use of chemotherapy and radiation therapy protectants. J Clin Oncol 2009; 27:127.
  70. Seymour L, Bramwell V, Moran LA. Use of dexrazoxane as a cardioprotectant in patients receiving doxorubicin or epirubicin chemotherapy for the treatment of cancer. The Provincial Systemic Treatment Disease Site Group. Cancer Prev Control 1999; 3:145.
  71. Lopez M, Vici P, Di Lauro K, et al. Randomized prospective clinical trial of high-dose epirubicin and dexrazoxane in patients with advanced breast cancer and soft tissue sarcomas. J Clin Oncol 1998; 16:86.
  72. Swain SM. Adult multicenter trials using dexrazoxane to protect against cardiac toxicity. Semin Oncol 1998; 25:43.
  73. Swain SM, Whaley FS, Gerber MC, et al. Cardioprotection with dexrazoxane for doxorubicin-containing therapy in advanced breast cancer. J Clin Oncol 1997; 15:1318.
  74. Curran CF, Narang PK, Reynolds RD. Toxicity profile of dexrazoxane (Zinecard, ICRF-187, ADR-529, NSC-169780), a modulator of doxorubicin cardiotoxicity. Cancer Treat Rev 1991; 18:241.
  75. Speyer JL, Green MD, Zeleniuch-Jacquotte A, et al. ICRF-187 permits longer treatment with doxorubicin in women with breast cancer. J Clin Oncol 1992; 10:117.
  76. Swain SM, Vici P. The current and future role of dexrazoxane as a cardioprotectant in anthracycline treatment: expert panel review. J Cancer Res Clin Oncol 2004; 130:1.
  77. van Dalen EC, Caron HN, Dickinson HO, Kremer LC. Cardioprotective interventions for cancer patients receiving anthracyclines. Cochrane Database Syst Rev 2011; :CD003917.
  78. Kalay N, Basar E, Ozdogru I, et al. Protective effects of carvedilol against anthracycline-induced cardiomyopathy. J Am Coll Cardiol 2006; 48:2258.
  79. Cardinale D, Colombo A, Sandri MT, et al. Prevention of high-dose chemotherapy-induced cardiotoxicity in high-risk patients by angiotensin-converting enzyme inhibition. Circulation 2006; 114:2474.
  80. Information on the PRADA trial available online at http://www.clinicaltrials.gov/ct2/show/NCT01434134?term=PRADA&rank=2 (Accessed on December 14, 2012).
  81. Lipshultz SE, Lipsitz SR, Sallan SE, et al. Chronic progressive cardiac dysfunction years after doxorubicin therapy for childhood acute lymphoblastic leukemia. J Clin Oncol 2005; 23:2629.
  82. Steinherz LJ, Graham T, Hurwitz R, et al. Guidelines for cardiac monitoring of children during and after anthracycline therapy: report of the Cardiology Committee of the Childrens Cancer Study Group. Pediatrics 1992; 89:942.
  83. DeCara JM. Early detection of chemotherapy-related left ventricular dysfunction. Curr Cardiol Rep 2012; 14:334.
  84. Thavendiranathan P, Grant AD, Negishi T, et al. Reproducibility of echocardiographic techniques for sequential assessment of left ventricular ejection fraction and volumes: application to patients undergoing cancer chemotherapy. J Am Coll Cardiol 2013; 61:77.
  85. Armstrong GT, Plana JC, Zhang N, et al. Screening adult survivors of childhood cancer for cardiomyopathy: comparison of echocardiography and cardiac magnetic resonance imaging. J Clin Oncol 2012; 30:2876.
  86. Kremer LC, Caron HN. Anthracycline cardiotoxicity in children. N Engl J Med 2004; 351:120.
  87. Kuittinen T, Husso-Saastamoinen M, Sipola P, et al. Very acute cardiac toxicity during BEAC chemotherapy in non-Hodgkin's lymphoma patients undergoing autologous stem cell transplantation. Bone Marrow Transplant 2005; 36:1077.
  88. Oberholzer K, Kunz RP, Dittrich M, Thelen M. [Anthracycline-induced cardiotoxicity: cardiac MRI after treatment for childhood cancer]. Rofo 2004; 176:1245.
  89. Nousiainen T, Jantunen E, Vanninen E, Hartikainen J. Early decline in left ventricular ejection fraction predicts doxorubicin cardiotoxicity in lymphoma patients. Br J Cancer 2002; 86:1697.
  90. Jensen BV, Skovsgaard T, Nielsen SL. Functional monitoring of anthracycline cardiotoxicity: a prospective, blinded, long-term observational study of outcome in 120 patients. Ann Oncol 2002; 13:699.
  91. Meinardi MT, van Veldhuisen DJ, Gietema JA, et al. Prospective evaluation of early cardiac damage induced by epirubicin-containing adjuvant chemotherapy and locoregional radiotherapy in breast cancer patients. J Clin Oncol 2001; 19:2746.
  92. Steinherz LJ, Steinherz PG, Tan CT, et al. Cardiac toxicity 4 to 20 years after completing anthracycline therapy. JAMA 1991; 266:1672.
  93. Schwartz RG, McKenzie WB, Alexander J, et al. Congestive heart failure and left ventricular dysfunction complicating doxorubicin therapy. Seven-year experience using serial radionuclide angiocardiography. Am J Med 1987; 82:1109.
  94. Gottdiener JS, Mathisen DJ, Borer JS, et al. Doxorubicin cardiotoxicity: assessment of late left ventricular dysfunction by radionuclide cineangiography. Ann Intern Med 1981; 94:430.
  95. Cheitlin MD, Armstrong WF, Aurigemma GP, et al. ACC/AHA/ASE 2003 guideline update for the clinical application of echocardiography: summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/ASE Committee to Update the 1997 Guidelines for the Clinical Application of Echocardiography). Circulation 2003; 108:1146.
  96. Klocke FJ, Baird MG, Lorell BH, et al. ACC/AHA/ASNC guidelines for the clinical use of cardiac radionuclide imaging--executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/ASNC Committee to Revise the 1995 Guidelines for the Clinical Use of Cardiac Radionuclide Imaging). Circulation 2003; 108:1404.
  97. Doxorubicin Hydrochloride for Injection, USP. http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/050467s070lbl.pdf (Accessed on April 01, 2016).
  98. FDA-approved drug labeling for mitoxantrone available online at http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=23983.
  99. Lee BH, Goodenday LS, Muswick GJ, et al. Alterations in left ventricular diastolic function with doxorubicin therapy. J Am Coll Cardiol 1987; 9:184.
  100. Sabel MS, Levine EG, Hurd T, et al. Is MUGA scan necessary in patients with low-risk breast cancer before doxorubicin-based adjuvant therapy? Multiple gated acquisition. Am J Clin Oncol 2001; 24:425.
  101. Porea TJ, Dreyer ZE, Bricker JT, Mahoney DH Jr. Evaluation of left ventricular function in asymptomatic children about to undergo anthracycline-based chemotherapy for acute leukemia: an outcome study. J Pediatr Hematol Oncol 2001; 23:420.
  102. Jeyakumar A, DiPenta J, Snow S, et al. Routine cardiac evaluation in patients with early-stage breast cancer before adjuvant chemotherapy. Clin Breast Cancer 2012; 12:4.
  103. Ali MK, Buzdar AU, Ewer MS, et al. Noninvasive cardiac evaluation of patients receiving adriamycin-containing adjuvant chemotherapy (FAC) for stage II or III breast cancer. J Surg Oncol 1983; 23:212.
  104. Ewer MS, Lenihan DJ. Left ventricular ejection fraction and cardiotoxicity: is our ear really to the ground? J Clin Oncol 2008; 26:1201.
  105. Herman EH, Zhang J, Lipshultz SE, et al. Correlation between serum levels of cardiac troponin-T and the severity of the chronic cardiomyopathy induced by doxorubicin. J Clin Oncol 1999; 17:2237.
  106. Lipshultz SE, Rifai N, Sallan SE, et al. Predictive value of cardiac troponin T in pediatric patients at risk for myocardial injury. Circulation 1997; 96:2641.
  107. Auner HW, Tinchon C, Linkesch W, et al. Prolonged monitoring of troponin T for the detection of anthracycline cardiotoxicity in adults with hematological malignancies. Ann Hematol 2003; 82:218.
  108. Cardinale D, Sandri MT, Martinoni A, et al. Myocardial injury revealed by plasma troponin I in breast cancer treated with high-dose chemotherapy. Ann Oncol 2002; 13:710.
  109. Cardinale D, Sandri MT, Colombo A, et al. Prognostic value of troponin I in cardiac risk stratification of cancer patients undergoing high-dose chemotherapy. Circulation 2004; 109:2749.
  110. Specchia G, Buquicchio C, Pansini N, et al. Monitoring of cardiac function on the basis of serum troponin I levels in patients with acute leukemia treated with anthracyclines. J Lab Clin Med 2005; 145:212.
  111. Ky B, Putt M, Sawaya H, et al. Early increases in multiple biomarkers predict subsequent cardiotoxicity in patients with breast cancer treated with doxorubicin, taxanes, and trastuzumab. J Am Coll Cardiol 2014; 63:809.
  112. Kremer LC, Bastiaansen BA, Offringa M, et al. Troponin T in the first 24 hours after the administration of chemotherapy and the detection of myocardial damage in children. Eur J Cancer 2002; 38:686.
  113. Raderer M, Kornek G, Weinländer G, Kastner J. Serum troponin T levels in adults undergoing anthracycline therapy. J Natl Cancer Inst 1997; 89:171.
  114. Fink FM, Genser N, Fink C, et al. Cardiac troponin T and creatine kinase MB mass concentrations in children receiving anthracycline chemotherapy. Med Pediatr Oncol 1995; 25:185.
  115. Kismet E, Varan A, Ayabakan C, et al. Serum troponin T levels and echocardiographic evaluation in children treated with doxorubicin. Pediatr Blood Cancer 2004; 42:220.
  116. Mathew P, Suarez W, Kip K, et al. Is there a potential role for serum cardiac troponin I as a marker for myocardial dysfunction in pediatric patients receiving anthracycline-based therapy? A pilot study. Cancer Invest 2001; 19:352.
  117. Soker M, Kervancioglu M. Plasma concentrations of NT-pro-BNP and cardiac troponin-I in relation to doxorubicin-induced cardiomyopathy and cardiac function in childhood malignancy. Saudi Med J 2005; 26:1197.
  118. Dodos F, Halbsguth T, Erdmann E, Hoppe UC. Usefulness of myocardial performance index and biochemical markers for early detection of anthracycline-induced cardiotoxicity in adults. Clin Res Cardiol 2008; 97:318.
  119. Germanakis I, Anagnostatou N, Kalmanti M. Troponins and natriuretic peptides in the monitoring of anthracycline cardiotoxicity. Pediatr Blood Cancer 2008; 51:327.
  120. Lipshultz SE, Rifai N, Dalton VM, et al. The effect of dexrazoxane on myocardial injury in doxorubicin-treated children with acute lymphoblastic leukemia. N Engl J Med 2004; 351:145.
  121. Bryant J, Picot J, Baxter L, et al. Use of cardiac markers to assess the toxic effects of anthracyclines given to children with cancer: a systematic review. Eur J Cancer 2007; 43:1959.
  122. Vogelsang TW, Jensen RJ, Hesse B, Kjaer A. BNP cannot replace gated equilibrium radionuclide ventriculography in monitoring of anthracycline-induced cardiotoxity. Int J Cardiol 2008; 124:193.
  123. Tikanoja T, Riikonen P, Perkkiö M, Helenius T. Serum N-terminal atrial natriuretic peptide (NT-ANP) in the cardiac follow-up in children with cancer. Med Pediatr Oncol 1998; 31:73.
  124. Mavinkurve-Groothuis AM, Kapusta L, Nir A, Groot-Loonen J. The role of biomarkers in the early detection of anthracycline-induced cardiotoxicity in children: a review of the literature. Pediatr Hematol Oncol 2008; 25:655.
  125. Lenihan DJ, Esteva FJ. Multidisciplinary strategy for managing cardiovascular risks when treating patients with early breast cancer. Oncologist 2008; 13:1224.
  126. Aggarwal S, Pettersen MD, Bhambhani K, et al. B-type natriuretic peptide as a marker for cardiac dysfunction in anthracycline-treated children. Pediatr Blood Cancer 2007; 49:812.
  127. Nousiainen T, Vanninen E, Jantunen E, et al. Natriuretic peptides during the development of doxorubicin-induced left ventricular diastolic dysfunction. J Intern Med 2002; 251:228.
  128. Thelander B. Trauma and dissociation. Perspect Psychiatr Care 2001; 37:4.
  129. Snowden JA, Hill GR, Hunt P, et al. Assessment of cardiotoxicity during haemopoietic stem cell transplantation with plasma brain natriuretic peptide. Bone Marrow Transplant 2000; 26:309.
  130. Poutanen T, Tikanoja T, Riikonen P, et al. Long-term prospective follow-up study of cardiac function after cardiotoxic therapy for malignancy in children. J Clin Oncol 2003; 21:2349.
  131. Sandri MT, Salvatici M, Cardinale D, et al. N-terminal pro-B-type natriuretic peptide after high-dose chemotherapy: a marker predictive of cardiac dysfunction? Clin Chem 2005; 51:1405.
  132. Germanakis I, Kalmanti M, Parthenakis F, et al. Correlation of plasma N-terminal pro-brain natriuretic peptide levels with left ventricle mass in children treated with anthracyclines. Int J Cardiol 2006; 108:212.
  133. Cooper LT, Baughman KL, Feldman AM, et al. The role of endomyocardial biopsy in the management of cardiovascular disease: a scientific statement from the American Heart Association, the American College of Cardiology, and the European Society of Cardiology. Circulation 2007; 116:2216.
  134. Meinardi MT, van der Graaf WT, van Veldhuisen DJ, et al. Detection of anthracycline-induced cardiotoxicity. Cancer Treat Rev 1999; 25:237.
  135. Yoon GJ, Telli ML, Kao DP, et al. Left ventricular dysfunction in patients receiving cardiotoxic cancer therapies are clinicians responding optimally? J Am Coll Cardiol 2010; 56:1644.
  136. Haq MM, Legha SS, Choksi J, et al. Doxorubicin-induced congestive heart failure in adults. Cancer 1985; 56:1361.
  137. Ajijola OA, Nandigam KV, Chabner BA, et al. Usefulness of cardiac resynchronization therapy in the management of Doxorubicin-induced cardiomyopathy. Am J Cardiol 2008; 101:1371.
  138. Mulrooney DA, Yeazel M, Mitby P, et al. Cardiovascular disease in adult survivors of childhood and adolescent cancer: A report from the Childhood Cancer Survivor Study (CCSS) (abstract). J Clin Oncol 2008; 26:504s.
  139. Nysom K, Holm K, Lipsitz SR, et al. Relationship between cumulative anthracycline dose and late cardiotoxicity in childhood acute lymphoblastic leukemia. J Clin Oncol 1998; 16:545.
  140. Bu'Lock FA, Mott MG, Oakhill A, Martin RP. Left ventricular diastolic function after anthracycline chemotherapy in childhood: relation with systolic function, symptoms, and pathophysiology. Br Heart J 1995; 73:340.
  141. Green DM, Grigoriev YA, Nan B, et al. Congestive heart failure after treatment for Wilms' tumor: a report from the National Wilms' Tumor Study group. J Clin Oncol 2001; 19:1926.
  142. Kremer LC, van der Pal HJ, Offringa M, et al. Frequency and risk factors of subclinical cardiotoxicity after anthracycline therapy in children: a systematic review. Ann Oncol 2002; 13:819.
  143. Lipshultz SE, Lipsitz SR, Mone SM, et al. Female sex and drug dose as risk factors for late cardiotoxic effects of doxorubicin therapy for childhood cancer. N Engl J Med 1995; 332:1738.
  144. Steinherz LJ, Steinherz PG, Tan C. Cardiac failure and dysrhythmias 6-19 years after anthracycline therapy: a series of 15 patients. Med Pediatr Oncol 1995; 24:352.
  145. Grenier MA, Lipshultz SE. Epidemiology of anthracycline cardiotoxicity in children and adults. Semin Oncol 1998; 25:72.
  146. Pein F, Sakiroglu O, Dahan M, et al. Cardiac abnormalities 15 years and more after adriamycin therapy in 229 childhood survivors of a solid tumour at the Institut Gustave Roussy. Br J Cancer 2004; 91:37.
  147. van Dalen EC, van der Pal HJ, Kok WE, et al. Clinical heart failure in a cohort of children treated with anthracyclines: a long-term follow-up study. Eur J Cancer 2006; 42:3191.
  148. Hudson MM, Rai SN, Nunez C, et al. Noninvasive evaluation of late anthracycline cardiac toxicity in childhood cancer survivors. J Clin Oncol 2007; 25:3635.
  149. O'Brien MM, Taub JW, Chang MN, et al. Cardiomyopathy in children with Down syndrome treated for acute myeloid leukemia: a report from the Children's Oncology Group Study POG 9421. J Clin Oncol 2008; 26:414.
  150. Sorensen K, Levitt GA, Bull C, et al. Late anthracycline cardiotoxicity after childhood cancer: a prospective longitudinal study. Cancer 2003; 97:1991.
  151. Lipshultz SE, Miller TL, Lipsitz SR, et al. Continuous Versus Bolus Infusion of Doxorubicin in Children With ALL: Long-term Cardiac Outcomes. Pediatrics 2012; 130:1003.
  152. Lipshultz SE, Giantris AL, Lipsitz SR, et al. Doxorubicin administration by continuous infusion is not cardioprotective: the Dana-Farber 91-01 Acute Lymphoblastic Leukemia protocol. J Clin Oncol 2002; 20:1677.
  153. Gupta M, Steinherz PG, Cheung NK, Steinherz L. Late cardiotoxicity after bolus versus infusion anthracycline therapy for childhood cancers. Med Pediatr Oncol 2003; 40:343.
  154. Wexler LH, Andrich MP, Venzon D, et al. Randomized trial of the cardioprotective agent ICRF-187 in pediatric sarcoma patients treated with doxorubicin. J Clin Oncol 1996; 14:362.
  155. Moghrabi A, Levy DE, Asselin B, et al. Results of the Dana-Farber Cancer Institute ALL Consortium Protocol 95-01 for children with acute lymphoblastic leukemia. Blood 2007; 109:896.
  156. Asselin B, Devidas M, Zhou T, et al. Cardioprotection and safety of dexrazoxane (DRZ) in children treated for newly diagnosed T-cell acute lymphblastic leukemia (T-ALL) or advanced stage lymphoblastic leukemia (T-LL). J Clin Oncol 2012; 30:15s. abst 9504.
  157. Lipshultz SE, Scully RE, Lipsitz SR, et al. Assessment of dexrazoxane as a cardioprotectant in doxorubicin-treated children with high-risk acute lymphoblastic leukaemia: long-term follow-up of a prospective, randomised, multicentre trial. Lancet Oncol 2010; 11:950.
  158. Armstrong GT, Kawashima T, Leisenring W, et al. Aging and risk of severe, disabling, life-threatening, and fatal events in the childhood cancer survivor study. J Clin Oncol 2014; 32:1218.
  159. Tebbi CK, London WB, Friedman D, et al. Dexrazoxane-associated risk for acute myeloid leukemia/myelodysplastic syndrome and other secondary malignancies in pediatric Hodgkin's disease. J Clin Oncol 2007; 25:493.
  160. Schwartz CL, Constine LS, Villaluna D, et al. A risk-adapted, response-based approach using ABVE-PC for children and adolescents with intermediate- and high-risk Hodgkin lymphoma: the results of P9425. Blood 2009; 114:2051.
  161. Chow EJ, Asselin BL, Schwartz CL, et al. Late Mortality After Dexrazoxane Treatment: A Report From the Children's Oncology Group. J Clin Oncol 2015; 33:2639.
  162. Bhatia S. Therapy-related myelodysplasia and acute myeloid leukemia. Semin Oncol 2013; 40:666.
  163. Shankar SM, Marina N, Hudson MM, et al. Monitoring for cardiovascular disease in survivors of childhood cancer: report from the Cardiovascular Disease Task Force of the Children's Oncology Group. Pediatrics 2008; 121:e387.
  164. Jannazzo A, Hoffman J, Lutz M. Monitoring of anthracycline-induced cardiotoxicity. Ann Pharmacother 2008; 42:99.
  165. Wong FL, Bhatia S, Landier W, et al. Cost-effectiveness of the children's oncology group long-term follow-up screening guidelines for childhood cancer survivors at risk for treatment-related heart failure. Ann Intern Med 2014; 160:672.
  166. Sieswerda E, Postma A, van Dalen EC, et al. The Dutch Childhood Oncology Group guideline for follow-up of asymptomatic cardiac dysfunction in childhood cancer survivors. Ann Oncol 2012; 23:2191.
  167. Landier W, Bhatia S, Eshelman DA, et al. Development of risk-based guidelines for pediatric cancer survivors: the Children's Oncology Group Long-Term Follow-Up Guidelines from the Children's Oncology Group Late Effects Committee and Nursing Discipline. J Clin Oncol 2004; 22:4979.
  168. Long-term follow-up guidelines from the Children's Oncology Group www.survivorshipguidelines.org/pdf/LTFUGuidelines.pdf (Accessed on May 10, 2011).
  169. Hamada H, Ohkubo T, Maeda M, Ogawa S. Evaluation of cardiac reserved function by high-dose dobutamine-stress echocardiography in asymptomatic anthracycline-treated survivors of childhood cancer. Pediatr Int 2006; 48:313.
  170. Lipshultz SE, Miller TL, Scully RE, et al. Changes in cardiac biomarkers during doxorubicin treatment of pediatric patients with high-risk acute lymphoblastic leukemia: associations with long-term echocardiographic outcomes. J Clin Oncol 2012; 30:1042.
  171. Lipshultz SE, Colan SD. Cardiovascular trials in long-term survivors of childhood cancer. J Clin Oncol 2004; 22:769.
  172. Silber JH, Cnaan A, Clark BJ, et al. Enalapril to prevent cardiac function decline in long-term survivors of pediatric cancer exposed to anthracyclines. J Clin Oncol 2004; 22:820.
  173. Lipshultz SE, Lipsitz SR, Sallan SE, et al. Long-term enalapril therapy for left ventricular dysfunction in doxorubicin-treated survivors of childhood cancer. J Clin Oncol 2002; 20:4517.