Pediatric Drugs

, Volume 16, Issue 5, pp 373–389 | Cite as

Managing Chemotherapy-Related Cardiotoxicity in Survivors of Childhood Cancers

  • Steven E. Lipshultz
  • Melissa B. Diamond
  • Vivian I. Franco
  • Sanjeev Aggarwal
  • Kasey Leger
  • Maria Verônica Santos
  • Stephen E. Sallan
  • Eric J. Chow
Review Article


In the US, children diagnosed with cancer are living longer, but not without consequences from the same drugs that cured their cancer. In these patients, cardiovascular disease is the leading cause of non-cancer-related morbidity and mortality. Although this review focuses on anthracycline-related cardiomyopathy in childhood cancer survivors, the global lifetime risk of other cardiovascular diseases such as atherosclerosis, arrhythmias and intracardiac conduction abnormalities, hypertension, and stroke also are increased. Besides anthracyclines, newer molecularly targeted agents, such as vascular endothelial growth factor receptor and tyrosine kinase inhibitors, also have been associated with acute hypertension, cardiomyopathy, and increased risk of ischemic cardiac events and arrhythmias, and are summarized here. This review also covers other risk factors for chemotherapy-related cardiotoxicity (including both modifiable and non-modifiable factors), monitoring strategies (including both blood and imaging-based biomarkers) during and following cancer treatment, and discusses the management of cardiotoxicity (including prevention strategies such as cardioprotection by use of dexrazoxane).


Imatinib Trastuzumab Left Ventricular Ejection Fraction Acute Lymphoblastic Leukemia Sorafenib 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The authors have no conflicts of interest that are directly relevant to the content of this review. Eric Chow is supported by grants from the National Cancer Institute (K07 CA151775), the Leukemia and Lymphoma Society, and the St. Baldricks’ Foundation.


  1. 1.
    American Cancer Society. Cancer Facts & Figures 2013. 2013.Google Scholar
  2. 2.
    Lipshultz SE, Colan SD, Gelber RD, Perez-Atayde AR, Sallan SE, Sanders SP. Late cardiac effects of doxorubicin therapy for acute lymphoblastic leukemia in childhood. N Engl J Med. 1991;324(12):808–15.PubMedGoogle Scholar
  3. 3.
    Mertens AC, Liu Q, Neglia JP, Wasilewski K, Leisenring W, Armstrong GT, et al. Cause-specific late mortality among 5-year survivors of childhood cancer: the Childhood Cancer Survivor Study. J Natl Cancer Inst. 2008;100(19):1368–79. doi: 10.1093/jnci/djn310.PubMedPubMedCentralGoogle Scholar
  4. 4.
    Tukenova M, Guibout C, Oberlin O, Doyon F, Mousannif A, Haddy N, et al. Role of cancer treatment in long-term overall and cardiovascular mortality after childhood cancer. J Clin Oncol. 2010;28(8):1308–15. doi: 10.1200/JCO.2008.20.2267.PubMedGoogle Scholar
  5. 5.
    Lipshultz SE, Alvarez JA, Scully RE. Anthracycline associated cardiotoxicity in survivors of childhood cancer. Heart. 2008;94(4):525–33. doi: 10.1136/hrt.2007.136093.PubMedGoogle Scholar
  6. 6.
    Von Hoff DD, Layard MW, Basa P, Davis HL Jr, Von Hoff AL, Rozencweig M, et al. Risk factors for doxorubicin-induced congestive heart failure. Ann Intern Med. 1979;91(5):710–7.Google Scholar
  7. 7.
    Lipshultz SE, Lipsitz SR, Mone SM, Goorin AM, Sallan SE, Sanders SP, 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(26):1738–43.PubMedGoogle Scholar
  8. 8.
    Orgel E, Zung L, Ji L, Finklestein J, Feusner J, Freyer DR. Early cardiac outcomes following contemporary treatment for childhood acute myeloid leukemia: a North American perspective. Pediatr Blood Cancer. 2013;60(9):1528–33. doi: 10.1002/pbc.24498.PubMedGoogle Scholar
  9. 9.
    Hudson MM, Rai SN, Nunez C, Merchant TE, Marina NM, Zalamea N, et al. Noninvasive evaluation of late anthracycline cardiac toxicity in childhood cancer survivors. J Clin Oncol. 2007;25(24):3635–43. doi: 10.1200/jco.2006.09.7451.PubMedGoogle Scholar
  10. 10.
    Trachtenberg BH, Landy DC, Franco VI, Henkel JM, Pearson EJ, Miller TL, et al. Anthracycline-associated cardiotoxicity in survivors of childhood cancer. Pediatr Cardiol. 2011;32(3):342–53. doi: 10.1007/s00246-010-9878-3.PubMedGoogle Scholar
  11. 11.
    Simbre VC, Duffy SA, Dadlani GH, Miller TL, Lipshultz SE. Cardiotoxicity of cancer chemotherapy: implications for children. Paediatr Drugs. 2005;7(3):187–202.PubMedGoogle Scholar
  12. 12.
    Lipshultz SE, Miller TL, Lipsitz SR, Neuberg DS, Dahlberg SE, Colan SD, et al. Continuous versus bolus infusion of doxorubicin in children with ALL: long-term cardiac outcomes. Pediatrics. 2012;130(6):1003–11. doi: 10.1542/peds.2012-0727.PubMedPubMedCentralGoogle Scholar
  13. 13.
    Lipshultz SE, Giantris AL, Lipsitz SR, Kimball Dalton V, Asselin BL, Barr RD et al. Doxorubicin administration by continuous infusion is not cardioprotective: the Dana-Farber 91-01 Acute Lymphoblastic Leukemia protocol. J Clin Oncol. 2002;20(6):1677–82.Google Scholar
  14. 14.
    Adams MJ, Lipshultz SE. Pathophysiology of anthracycline- and radiation-associated cardiomyopathies: implications for screening and prevention. Pediatr Blood Cancer. 2005;44(7):600–6. doi: 10.1002/pbc.20352.PubMedGoogle Scholar
  15. 15.
    Gilladoga AC, Manuel C, Tan CT, Wollner N, Sternberg SS, Murphy ML. The cardiotoxicity of adriamycin and daunomycin in children. Cancer. 1976;37(2 Suppl):1070–8.PubMedGoogle Scholar
  16. 16.
    Little MP, Azizova TV, Bazyka D, Bouffler SD, Cardis E, Chekin S, et al. Systematic review and meta-analysis of circulatory disease from exposure to low-level ionizing radiation and estimates of potential population mortality risks. Environ Health Perspect. 2012;120(11):1503–11. doi: 10.1289/ehp.1204982.PubMedPubMedCentralGoogle Scholar
  17. 17.
    Heidenreich PA, Schnittger I, Strauss HW, Vagelos RH, Lee BK, Mariscal CS, et al. Screening for coronary artery disease after mediastinal irradiation for Hodgkin’s disease. J Clin Oncol. 2007;25(1):43–9. doi: 10.1200/jco.2006.07.0805.PubMedGoogle Scholar
  18. 18.
    Adams MJ, Lipsitz SR, Colan SD, Tarbell NJ, Treves ST, Diller L, et al. Cardiovascular status in long-term survivors of Hodgkin’s disease treated with chest radiotherapy. J Clin Oncol. 2004;22(15):3139–48. doi: 10.1200/JCO.2004.09.109.PubMedGoogle Scholar
  19. 19.
    Landy DC, Miller TL, Lipsitz SR, Lopez-Mitnik G, Hinkle AS, Constine LS, et al. Cranial irradiation as an additional risk factor for anthracycline cardiotoxicity in childhood cancer survivors: an analysis from the cardiac risk factors in childhood cancer survivors study. Pediatr Cardiol. 2013;34(4):826–34. doi: 10.1007/s00246-012-0539-6.PubMedPubMedCentralGoogle Scholar
  20. 20.
    Lipshultz SE, Landy DC, Lopez-Mitnik G, Lipsitz SR, Hinkle AS, Constine LS, et al. Cardiovascular status of childhood cancer survivors exposed and unexposed to cardiotoxic therapy. J Clin Oncol. 2012;30(10):1050–7. doi: 10.1200/JCO.2010.33.7907.PubMedPubMedCentralGoogle Scholar
  21. 21.
    Lipshultz SE, Cochran TR, Franco VI, Miller TL. Treatment-related cardiotoxicity in survivors of childhood cancer. Nat Rev Clin Oncol. 2013;10:697–710. doi: 10.1038/nrclinonc.2013.195.PubMedGoogle Scholar
  22. 22.
    Landy DC, Lipsitz SR, Kurtz JM, Hinkle AS, Constine LS, Adams MJ, et al. Dietary quality, caloric intake, and adiposity of childhood cancer survivors and their siblings: an analysis from the cardiac risk factors in childhood cancer survivors study. Nutr Cancer. 2013;65(4):547–55. doi: 10.1080/01635581.2013.770042.PubMedGoogle Scholar
  23. 23.
    Landy DC, Miller TL, Lopez-Mitnik G, Lipsitz SR, Hinkle AS, Constine LS et al. Aggregating traditional cardiovascular disease risk factors to assess the cardiometabolic health of childhood cancer survivors: an analysis from the Cardiac Risk Factors in Childhood Cancer Survivors Study. Am Heart J. 2012;163(2):295–301 e2. doi: 10.1016/j.ahj.2011.11.008.
  24. 24.
    Miller TL, Lipsitz SR, Lopez-Mitnik G, Hinkle AS, Constine LS, Adams MJ, et al. Characteristics and determinants of adiposity in pediatric cancer survivors. Cancer Epidemiol Biomark Prev. 2010;19(8):2013–22. doi: 10.1158/1055-9965.EPI-10-0163.Google Scholar
  25. 25.
    Miller AM, Lopez-Mitnik G, Somarriba G, Lipsitz SR, Hinkle AS, Constine LS, et al. Exercise capacity in long-term survivors of pediatric cancer: an analysis from the Cardiac Risk Factors in Childhood Cancer Survivors Study. Pediatr Blood Cancer. 2013;60(4):663–8. doi: 10.1002/pbc.24410.PubMedGoogle Scholar
  26. 26.
    Ness KK, Leisenring WM, Huang S, Hudson MM, Gurney JG, Whelan K, et al. Predictors of inactive lifestyle among adult survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. Cancer. 2009;115(9):1984–94. doi: 10.1002/cncr.24209.PubMedPubMedCentralGoogle Scholar
  27. 27.
    van Laar M, Feltbower RG, Gale CP, Bowen DT, Oliver SE, Glaser A. Cardiovascular sequelae in long-term survivors of young peoples’ cancer: a linked cohort study. Br J Cancer. 2014;. doi: 10.1038/bjc.2014.37.Google Scholar
  28. 28.
    Armstrong GT, Oeffinger KC, Chen Y, Kawashima T, Yasui Y, Leisenring W, et al. Modifiable risk factors and major cardiac events among adult survivors of childhood cancer. J Clin Oncol. 2013;31(29):3673–80. doi: 10.1200/jco.2013.49.3205.PubMedGoogle Scholar
  29. 29.
    Messiah SE, Arheart KL, Lopez-Mitnik G, Lipshultz SE, Miller TL. Ethnic group differences in cardiometabolic disease risk factors independent of body mass index among American youth. Obesity (Silver Spring). 2013;21(3):424–8. doi: 10.1002/oby.20343.PubMedPubMedCentralGoogle Scholar
  30. 30.
    Meacham LR, Sklar CA, Li S, Liu Q, Gimpel N, Yasui Y, et al. Diabetes mellitus in long-term survivors of childhood cancer. Increased risk associated with radiation therapy: a report for the childhood cancer survivor study. Arch Intern Med. 2009;169(15):1381–8. doi: 10.1001/archinternmed.2009.209.PubMedPubMedCentralGoogle Scholar
  31. 31.
    Emmons KM, Puleo E, Mertens A, Gritz ER, Diller L, Li FP. Long-term smoking cessation outcomes among childhood cancer survivors in the Partnership for Health Study. J Clin Oncol. 2009;27(1):52–60. doi: 10.1200/jco.2007.13.0880.PubMedPubMedCentralGoogle Scholar
  32. 32.
    Klosky JL, Howell CR, Li Z, Foster RH, Mertens AC, Robison LL, et al. Risky health behavior among adolescents in the childhood cancer survivor study cohort. J Pediatr Psychol. 2012;37(6):634–46.PubMedPubMedCentralGoogle Scholar
  33. 33.
    Lipshultz SE, Lipsitz SR, Sallan SE, Dalton VM, Mone SM, Gelber RD, et al. Chronic progressive cardiac dysfunction years after doxorubicin therapy for childhood acute lymphoblastic leukemia. J Clin Oncol. 2005;23(12):2629–36. doi: 10.1200/jco.2005.12.121.PubMedGoogle Scholar
  34. 34.
    Swain SM, Whaley FS, Ewer MS. Congestive heart failure in patients treated with doxorubicin: a retrospective analysis of three trials. Cancer. 2003;97(11):2869–79. doi: 10.1002/cncr.11407.PubMedGoogle Scholar
  35. 35.
    Lipshultz SE, Scully RE, Lipsitz SR, Sallan SE, Silverman LB, Miller TL, 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(10):950–61. doi: 10.1016/S1470-2045(10)70204-7.PubMedPubMedCentralGoogle Scholar
  36. 36.
    Lipshultz SE, Rifai N, Dalton VM, Levy DE, Silverman LB, Lipsitz SR, et al. The effect of dexrazoxane on myocardial injury in doxorubicin-treated children with acute lymphoblastic leukemia. N Engl J Med. 2004;351(2):145–53. doi: 10.1056/NEJMoa035153.PubMedGoogle Scholar
  37. 37.
    Lipshultz SE, Lipsitz SR, Kutok JL, Miller TL, Colan SD, Neuberg DS, et al. Impact of hemochromatosis gene mutations on cardiac status in doxorubicin-treated survivors of childhood high-risk leukemia. Cancer. 2013;119(19):3555–62. doi: 10.1002/cncr.28256.PubMedGoogle Scholar
  38. 38.
    Blanco JG, Leisenring WM, Gonzalez-Covarrubias VM, Kawashima TI, Davies SM, Relling MV, et al. Genetic polymorphisms in the carbonyl reductase 3 gene CBR3 and the NAD(P)H:quinone oxidoreductase 1 gene NQO1 in patients who developed anthracycline-related congestive heart failure after childhood cancer. Cancer. 2008;112(12):2789–95. doi: 10.1002/cncr.23534.PubMedGoogle Scholar
  39. 39.
    Blanco JG, Sun CL, Landier W, Chen L, Esparza-Duran D, Leisenring W, et al. Anthracycline-related cardiomyopathy after childhood cancer: role of polymorphisms in carbonyl reductase genes–a report from the Children’s Oncology Group. J Clin Oncol. 2012;30(13):1415–21. doi: 10.1200/jco.2011.34.8987.PubMedPubMedCentralGoogle Scholar
  40. 40.
    Visscher H, Ross CJ, Rassekh SR, Barhdadi A, Dube MP, Al-Saloos H, et al. Pharmacogenomic prediction of anthracycline-induced cardiotoxicity in children. J Clin Oncol. 2012;30(13):1422–8. doi: 10.1200/jco.2010.34.3467.PubMedGoogle Scholar
  41. 41.
    Visscher H, Ross CJ, Rassekh SR, Sandor GS, Caron HN, van Dalen EC, et al. Validation of variants in SLC28A3 and UGT1A6 as genetic markers predictive of anthracycline-induced cardiotoxicity in children. Pediatr Blood Cancer. 2013;60(8):1375–81. doi: 10.1002/pbc.24505.PubMedGoogle Scholar
  42. 42.
    Miranda CJ, Makui H, Soares RJ, Bilodeau M, Mui J, Vali H, et al. Hfe deficiency increases susceptibility to cardiotoxicity and exacerbates changes in iron metabolism induced by doxorubicin. Blood. 2003;102(7):2574–80. doi: 10.1182/blood-2003-03-0869.PubMedGoogle Scholar
  43. 43.
    Krischer JP, Epstein S, Cuthbertson DD, Goorin AM, Epstein ML, Lipshultz SE. Clinical cardiotoxicity following anthracycline treatment for childhood cancer: the Pediatric Oncology Group experience. J Clin Oncol. 1997;15(4):1544–52.PubMedGoogle Scholar
  44. 44.
    de Lemos JA, Drazner MH, Omland T, Ayers CR, Khera A, Rohatgi A, et al. Association of troponin T detected with a highly sensitive assay and cardiac structure and mortality risk in the general population. JAMA. 2010;304(22):2503–12. doi: 10.1001/jama.2010.1768.PubMedGoogle Scholar
  45. 45.
    Morrow DA, Cannon CP, Jesse RL, Newby LK, Ravkilde J, Storrow AB, et al. National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines: Clinical characteristics and utilization of biochemical markers in acute coronary syndromes. Circulation. 2007;115(13):e356–75. doi: 10.1161/circulationaha.107.182882.PubMedGoogle Scholar
  46. 46.
    Cardinale D, Sandri MT, Colombo A, Colombo N, Boeri M, Lamantia G, et al. Prognostic value of troponin I in cardiac risk stratification of cancer patients undergoing high-dose chemotherapy. Circulation. 2004;109(22):2749–54. doi: 10.1161/ Scholar
  47. 47.
    Cardinale D, Colombo A, Sandri MT, Lamantia G, Colombo N, Civelli M, et al. Prevention of high-dose chemotherapy-induced cardiotoxicity in high-risk patients by angiotensin-converting enzyme inhibition. Circulation. 2006;114(23):2474–81. doi: 10.1161/circulationaha.106.635144.PubMedGoogle Scholar
  48. 48.
    Colombo A, Meroni CA, Cipolla CM, Cardinale D. Managing cardiotoxicity of chemotherapy. Curr Treat Options Cardiovasc Med. 2013;15(4):410–24. doi: 10.1007/s11936-013-0248-3.PubMedGoogle Scholar
  49. 49.
    Lipshultz SE, Miller TL, Scully RE, Lipsitz SR, Rifai N, Silverman LB, 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(10):1042–9. doi: 10.1200/jco.2010.30.3404.PubMedPubMedCentralGoogle Scholar
  50. 50.
    Ekstein S, Nir A, Rein AJ, Perles Z, Bar-Oz B, Salpeter L, et al. N-terminal-proB-type natriuretic peptide as a marker for acute anthracycline cardiotoxicity in children. J Pediatr Hematol Oncol. 2007;29(7):440–4. doi: 10.1097/MPH.0b013e3180640d42.PubMedGoogle Scholar
  51. 51.
    Erkus B, Demirtas S, Yarpuzlu AA, Can M, Genc Y, Karaca L. Early prediction of anthracycline induced cardiotoxicity. Acta Paediatr. 2007;96(4):506–9. doi: 10.1111/j.1651-2227.2006.00174.x.PubMedGoogle Scholar
  52. 52.
    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(8):1197–202.PubMedGoogle Scholar
  53. 53.
    Braunwald E. Biomarkers in heart failure. N Engl J Med. 2008;358(20):2148–59. doi: 10.1056/NEJMra0800239.PubMedGoogle Scholar
  54. 54.
    Anand IS, Latini R, Florea VG, Kuskowski MA, Rector T, Masson S, et al. C-reactive protein in heart failure: prognostic value and the effect of valsartan. Circulation. 2005;112(10):1428–34. doi: 10.1161/circulationaha.104.508465.PubMedGoogle Scholar
  55. 55.
    Vasan RS, Sullivan LM, Roubenoff R, Dinarello CA, Harris T, Benjamin EJ, et al. Inflammatory markers and risk of heart failure in elderly subjects without prior myocardial infarction: the Framingham Heart Study. Circulation. 2003;107(11):1486–91.PubMedGoogle Scholar
  56. 56.
    Lee DS, Vasan RS. Novel markers for heart failure diagnosis and prognosis. Curr Opin Cardiol. 2005;20(3):201–10.PubMedGoogle Scholar
  57. 57.
    Dessi M, Madeddu C, Piras A, Cadeddu C, Antoni G, Mercuro G, et al. Long-term, up to 18 months, protective effects of the angiotensin II receptor blocker telmisartan on Epirubin-induced inflammation and oxidative stress assessed by serial strain rate. Springerplus. 2013;2(1):198. doi: 10.1186/2193-1801-2-198.PubMedPubMedCentralGoogle Scholar
  58. 58.
    Xie L, Terrand J, Xu B, Tsaprailis G, Boyer J, Chen QM. Cystatin C increases in cardiac injury: a role in extracellular matrix protein modulation. Cardiovasc Res. 2010;87(4):628–35. doi: 10.1093/cvr/cvq138.PubMedPubMedCentralGoogle Scholar
  59. 59.
    Patel PC, Ayers CR, Murphy SA, Peshock R, Khera A, de Lemos JA, et al. Association of cystatin C with left ventricular structure and function: the Dallas Heart Study. Circ Heart Fail. 2009;2(2):98–104. doi: 10.1161/circheartfailure.108.807271.PubMedGoogle Scholar
  60. 60.
    Ix JH, Shlipak MG, Chertow GM, Whooley MA. Association of cystatin C with mortality, cardiovascular events, and incident heart failure among persons with coronary heart disease: data from the Heart and Soul Study. Circulation. 2007;115(2):173–9. doi: 10.1161/circulationaha.106.644286.PubMedPubMedCentralGoogle Scholar
  61. 61.
    Gupta S, Drazner MH, de Lemos JA. Newer biomarkers in heart failure. Heart Fail Clin. 2009;5(4):579–88. doi: 10.1016/j.hfc.2009.04.004.PubMedGoogle Scholar
  62. 62.
    de Boer RA, Voors AA, Muntendam P, van Gilst WH, van Veldhuisen DJ. Galectin-3: a novel mediator of heart failure development and progression. Eur J Heart Fail. 2009;11(9):811–7. doi: 10.1093/eurjhf/hfp097.PubMedGoogle Scholar
  63. 63.
    Lok DJ, Van Der Meer P, de la Porte PW, Lipsic E, Van Wijngaarden J, Hillege HL, et al. Prognostic value of galectin-3, a novel marker of fibrosis, in patients with chronic heart failure: data from the DEAL-HF study. Clin Res Cardiol. 2010;99(5):323–8. doi: 10.1007/s00392-010-0125-y.PubMedPubMedCentralGoogle Scholar
  64. 64.
    van Rooij E, Olson EN. MicroRNA therapeutics for cardiovascular disease: opportunities and obstacles. Nat Rev Drug Discov. 2012;11(11):860–72. doi: 10.1038/nrd3864.PubMedGoogle Scholar
  65. 65.
    Fichtlscherer S, Zeiher AM, Dimmeler S. Circulating microRNAs: biomarkers or mediators of cardiovascular diseases? Arterioscler Thromb Vasc Biol. 2011;31(11):2383–90. doi: 10.1161/atvbaha.111.226696.PubMedGoogle Scholar
  66. 66.
    Horie T, Ono K, Nishi H, Nagao K, Kinoshita M, Watanabe S, et al. Acute doxorubicin cardiotoxicity is associated with miR-146a-induced inhibition of the neuregulin-ErbB pathway. Cardiovasc Res. 2010;87(4):656–64. doi: 10.1093/cvr/cvq148.PubMedPubMedCentralGoogle Scholar
  67. 67.
    Fu J, Peng C, Wang W, Jin H, Tang Q, Wei X. Let-7 g is involved in doxorubicin induced myocardial injury. Environ Toxicol Pharmacol. 2012;33(2):312–7. doi: 10.1016/j.etap.2011.12.023.PubMedGoogle Scholar
  68. 68.
    Steinherz LJ, Graham T, Hurwitz R, Sondheimer HM, Schwartz RG, Shaffer EM, 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(5 Pt 1):942–9.PubMedGoogle Scholar
  69. 69.
    Lipshultz SE, Sanders SP, Goorin AM, Krischer JP, Sallan SE, Colan SD. Monitoring for anthracycline cardiotoxicity. Pediatrics. 1994;93(3):433–7.PubMedGoogle Scholar
  70. 70.
    Poterucha JT, Kutty S, Lindquist RK, Li L, Eidem BW. Changes in left ventricular longitudinal strain with anthracycline chemotherapy in adolescents precede subsequent decreased left ventricular ejection fraction. J Am Soc Echocardiogr. 2012;25(7):733–40. doi: 10.1016/j.echo.2012.04.007.PubMedGoogle Scholar
  71. 71.
    Ruggiero A, De Rosa G, Rizzo D, Leo A, Maurizi P, De Nisco A, et al. Myocardial performance index and biochemical markers for early detection of doxorubicin-induced cardiotoxicity in children with acute lymphoblastic leukaemia. Int J Clin Oncol. 2013;18(5):927–33. doi: 10.1007/s10147-012-0458-9.PubMedGoogle Scholar
  72. 72.
    Jurcut R, Wildiers H, Ganame J, D’Hooge J, De Backer J, Denys H, et al. Strain rate imaging detects early cardiac effects of pegylated liposomal Doxorubicin as adjuvant therapy in elderly patients with breast cancer. J Am Soc Echocardiogr. 2008;21(12):1283–9.PubMedGoogle Scholar
  73. 73.
    Stoodley PW, Richards DA, Hui R, Boyd A, Harnett PR, Meikle SR, et al. Two-dimensional myocardial strain imaging detects changes in left ventricular systolic function immediately after anthracycline chemotherapy. Eur J Echocardiogr. 2011;12(12):945–52. doi: 10.1093/ejechocard/jer187.PubMedGoogle Scholar
  74. 74.
    Sawaya H, Sebag IA, Plana JC, Januzzi JL, Ky B, Cohen V, et al. Early detection and prediction of cardiotoxicity in chemotherapy-treated patients. Am J Cardiol. 2011;107(9):1375–80. doi: 10.1016/j.amjcard.2011.01.006.PubMedPubMedCentralGoogle Scholar
  75. 75.
    Ganame J, Claus P, Eyskens B, Uyttebroeck A, Renard M, D’Hooge J, et al. Acute cardiac functional and morphological changes after Anthracycline infusions in children. Am J Cardiol. 2007;99(7):974–7. doi: 10.1016/j.amjcard.2006.10.063.PubMedGoogle Scholar
  76. 76.
    Lunning MA, Kutty S, Rome ET, Li L, Padiyath A, Loberiza F, et al. Cardiac Magnetic Resonance Imaging for the Assessment of the Myocardium After Doxorubicin-based Chemotherapy. Am J Clin Oncol. 2013;21(12):1283–9.Google Scholar
  77. 77.
    Wassmuth R, Lentzsch S, Erdbruegger U, Schulz-Menger J, Doerken B, Dietz R, et al. Subclinical cardiotoxic effects of anthracyclines as assessed by magnetic resonance imaging-a pilot study. Am Heart J. 2001;141(6):1007–13. doi: 10.1067/mhj.2001.115436.PubMedGoogle Scholar
  78. 78.
    Oberholzer K, Kunz RP, Dittrich M, Thelen M. Anthracycline-induced cardiotoxicity: cardiac MRI after treatment for childhood cancer. Rofo. 2004;176(9):1245–50. doi: 10.1055/s-2004-813416.PubMedGoogle Scholar
  79. 79.
    Shankar SM, Marina N, Hudson MM, Hodgson DC, Adams MJ, Landier W, 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(2):e387–96. doi: 10.1542/peds.2007-0575.PubMedGoogle Scholar
  80. 80.
    Wong FL, Bhatia S, Landier W, Francisco L, Leisenring W, Hudson MM et al. Efficacy and cost-effectiveness of the Children’s Oncology Group long-term follow-Up guidelines for early detection of treatment-related cardiac compromise in childhood cancer survivors. Ann Intern Med. 2014;160(10):672–83. doi: 10.7326/M13-2498
  81. 81.
    Stapleton GE, Stapleton SL, Martinez A, Ayres NA, Kovalchin JP, Bezold LI, et al. Evaluation of longitudinal ventricular function with tissue Doppler echocardiography in children treated with anthracyclines. J Am Soc Echocardiogr. 2007;20(5):492–7. doi: 10.1016/j.echo.2006.10.011.PubMedGoogle Scholar
  82. 82.
    Bellenger NG, Burgess MI, Ray SG, Lahiri A, Coats AJ, Cleland JG, et al. Comparison of left ventricular ejection fraction and volumes in heart failure by echocardiography, radionuclide ventriculography and cardiovascular magnetic resonance; are they interchangeable? Eur Heart J. 2000;21(16):1387–96. doi: 10.1053/euhj.2000.2011.PubMedGoogle Scholar
  83. 83.
    Jenkins C, Bricknell K, Hanekom L, Marwick TH. Reproducibility and accuracy of echocardiographic measurements of left ventricular parameters using real-time three-dimensional echocardiography. J Am Coll Cardiol. 2004;44(4):878–86. doi: 10.1016/j.jacc.2004.05.050.PubMedGoogle Scholar
  84. 84.
    Eidem BW, Sapp BG, Suarez CR, Cetta F. Usefulness of the myocardial performance index for early detection of anthracycline-induced cardiotoxicity in children. Am J Cardiol. 2001;87(9):1120–2, A9.Google Scholar
  85. 85.
    Iarussi D, Indolfi P, Casale F, Martino V, Di Tullio MT, Calabro R. Anthracycline-induced cardiotoxicity in children with cancer: strategies for prevention and management. Paediatr Drugs. 2005;7(2):67–76.PubMedGoogle Scholar
  86. 86.
    Karakurt C, Kocak G, Ozgen U. Evaluation of the left ventricular function with tissue tracking and tissue Doppler echocardiography in pediatric malignancy survivors after anthracycline therapy. Echocardiography. 2008;25(8):880–7. doi: 10.1111/j.1540-8175.2008.00695.x.PubMedGoogle Scholar
  87. 87.
    Dorup I, Levitt G, Sullivan I, Sorensen K. Prospective longitudinal assessment of late anthracycline cardiotoxicity after childhood cancer: the role of diastolic function. Heart. 2004;90(10):1214–6. doi: 10.1136/hrt.2003.027516.PubMedPubMedCentralGoogle Scholar
  88. 88.
    Kapusta L, Thijssen JM, Groot-Loonen J, Antonius T, Mulder J, Daniels O. Tissue Doppler imaging in detection of myocardial dysfunction in survivors of childhood cancer treated with anthracyclines. Ultrasound Med Biol. 2000;26(7):1099–108.PubMedGoogle Scholar
  89. 89.
    Tsai HR, Gjesdal O, Wethal T, Haugaa KH, Fossa A, Fossa SD, et al. Left ventricular function assessed by two-dimensional speckle tracking echocardiography in long-term survivors of Hodgkin’s lymphoma treated by mediastinal radiotherapy with or without anthracycline therapy. Am J Cardiol. 2011;107(3):472–7. doi: 10.1016/j.amjcard.2010.09.048.PubMedGoogle Scholar
  90. 90.
    Motoki H, Koyama J, Nakazawa H, Aizawa K, Kasai H, Izawa A, et al. Torsion analysis in the early detection of anthracycline-mediated cardiomyopathy. Eur Heart J Cardiovasc Imaging. 2012;13(1):95–103. doi: 10.1093/ejechocard/jer172.PubMedGoogle Scholar
  91. 91.
    Cheung YF, Li SN, Chan GC, Wong SJ, Ha SY. Left ventricular twisting and untwisting motion in childhood cancer survivors. Echocardiography. 2011;28(7):738–45. doi: 10.1111/j.1540-8175.2011.01429.x.PubMedGoogle Scholar
  92. 92.
    Fallah-Rad N, Lytwyn M, Fang T, Kirkpatrick I, Jassal DS. Delayed contrast enhancement cardiac magnetic resonance imaging in trastuzumab induced cardiomyopathy. J Cardiovasc Magn Reson. 2008;10:5. doi: 10.1186/1532-429x-10-5.PubMedPubMedCentralGoogle Scholar
  93. 93.
    Dash R, Chung J, Chan T, Yamada M, Barral J, Nishimura D, et al. A molecular MRI probe to detect treatment of cardiac apoptosis in vivo. Magn Reson Med. 2011;66(4):1152–62. doi: 10.1002/mrm.22876.PubMedPubMedCentralGoogle Scholar
  94. 94.
    Minotti G, Recalcati S, Menna P, Salvatorelli E, Corna G, Cairo G. Doxorubicin cardiotoxicity and the control of iron metabolism: quinone-dependent and independent mechanisms. Methods Enzymol. 2004;378:340–61. doi: 10.1016/S0076-6879(04)78025-8.PubMedGoogle Scholar
  95. 95.
    Hensley ML, Hagerty KL, Kewalramani T, Green DM, Meropol NJ, Wasserman TH, et al. American Society of Clinical Oncology 2008 clinical practice guideline update: use of chemotherapy and radiation therapy protectants. J Clin Oncol. 2009;27(1):127–45. doi: 10.1200/JCO.2008.17.2627.PubMedGoogle Scholar
  96. 96.
    Kalam K, Marwick TH. Role of cardioprotective therapy for prevention of cardiotoxicity with chemotherapy: a systematic review and meta-analysis. Eur J Cancer. 2013;49(13):2900–9. doi: 10.1016/j.ejca.2013.04.030.PubMedGoogle Scholar
  97. 97.
    van Dalen EC, Caron HN, Dickinson HO, Kremer LC. Cardioprotective interventions for cancer patients receiving anthracyclines. Cochrane Database Syst Rev. 2011(6):CD003917. doi: 10.1002/14651858.CD003917.pub4.
  98. 98.
    Wexler LH, Andrich MP, Venzon D, Berg SL, Weaver-McClure L, Chen CC, et al. Randomized trial of the cardioprotective agent ICRF-187 in pediatric sarcoma patients treated with doxorubicin. J Clin Oncol. 1996;14(2):362–72.PubMedGoogle Scholar
  99. 99.
    Asselin B, Devidas M, Zhou T, Camitta BM, Lipshultz SE. Cardioprotection and safety of dexrazoxane (DRZ) in children treated for newly diagnosed T-cell acute lymphoblastic leukemia (T-ALL) or advanced stage lymphoblastic leukemia (T-LL). J Clin Oncol. 2012:9504 (abstract).Google Scholar
  100. 100.
    Ebb D, Meyers P, Grier H, Bernstein M, Gorlick R, Lipshultz SE, et al. Phase II trial of trastuzumab in combination with cytotoxic chemotherapy for treatment of metastatic osteosarcoma with human epidermal growth factor receptor 2 overexpression: a report from the children’s oncology group. J Clin Oncol. 2012;30(20):2545–51. doi: 10.1200/JCO.2011.37.4546.PubMedPubMedCentralGoogle Scholar
  101. 101.
    Kopp LM, Bernstein ML, Schwartz CL, Ebb D, Krailo MD, Grier HE et al. The effects of dexrazoxane on cardiac status and second malignant neoplasms (SMN) in doxorubicin-treated patients with osteosarcoma (OS). J Clin Oncol. 2012:9503 (abstract).Google Scholar
  102. 102.
    Vrooman LM, Neuberg DS, Stevenson KE, Asselin BL, Athale UH, Clavell L, et al. The low incidence of secondary acute myelogenous leukaemia in children and adolescents treated with dexrazoxane for acute lymphoblastic leukaemia: a report from the Dana-Farber Cancer Institute ALL Consortium. Eur J Cancer. 2011;47(9):1373–9. doi: 10.1016/j.ejca.2011.03.022.PubMedPubMedCentralGoogle Scholar
  103. 103.
    Tebbi CK, London WB, Friedman D, Villaluna D, De Alarcon PA, Constine LS, 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(5):493–500. doi: 10.1200/JCO.2005.02.3879.PubMedGoogle Scholar
  104. 104.
    Walker DM, Fisher BT, Seif AE, Huang YS, Torp K, Li Y, et al. Dexrazoxane use in pediatric patients with acute lymphoblastic or myeloid leukemia from 1999 and 2009: analysis of a national cohort of patients in the Pediatric Health Information Systems database. Pediatr Blood Cancer. 2013;60(4):616–20. doi: 10.1002/pbc.24270.PubMedPubMedCentralGoogle Scholar
  105. 105.
    Seif CE, Walker DM, Li Y, Huang YS, Kavcic M, Torp K et al. Dexrazoxane exposure and risk of secondary acute myeloid leukemia in pediatric cancer patients. Pediatr Blood Cancer. 2014. doi:  10.1002/pbc/25043 [Epub ahead of print].
  106. 106.
    Tebbi CK, Mendenhall NP, London WB, Williams JL, Hutchison RE, Fitzgerald TJ, et al. Response-dependent and reduced treatment in lower risk Hodgkin lymphoma in children and adolescents, results of P9426: a report from the Children’s Oncology Group. Pediatr Blood Cancer. 2012;59(7):1259–65. doi: 10.1002/pbc.24279.PubMedPubMedCentralGoogle Scholar
  107. 107.
    Schwartz CL, Constine LS, Villaluna D, London WB, Hutchison RE, Sposto R, 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(10):2051–9. doi: 10.1182/blood-2008-10-184143.PubMedPubMedCentralGoogle Scholar
  108. 108.
    Chow EJ, Asselin BL, Schwartz CL, Doody DR, Leisenring WM, Aggarwal S et al. Late mortality and relapse after dexrazoxane (DRZ) treatment: an update from the Children’s Oncology Group (COG). J Clin Oncol. 2014:10024 (abstract).Google Scholar
  109. 109.
    Gallegos-Castorena S, Martinez-Avalos A, Mohar-Betancourt A, Guerrero-Avendano G, Zapata-Tarres M, Medina-Sanson A. Toxicity prevention with amifostine in pediatric osteosarcoma patients treated with cisplatin and doxorubicin. Pediatr Hematol Oncol. 2007;24(6):403–8. doi: 10.1080/08880010701451244.PubMedGoogle Scholar
  110. 110.
    Myers DF, O’Connell JB, Subramanian R. Myocarditis resolving after discontinuation of procainamide. Int J Cardiol. 1983;4(3):322–4.PubMedGoogle Scholar
  111. 111.
    Wagdi P, Rouvinez G, Fluri M, Aeschbacher B, Thoni A, Schefer H et al. [Cardioprotection in chemo- and radiotherapy for malignant diseases–an echocardiographic pilot study]. Praxis (Bern 1994). 1995;84(43):1220–3.Google Scholar
  112. 112.
    Kraft J, Grille W, Appelt M, Hossfeld DK, Eichelbaum M, Koslowski B, et al. Effects of verapamil on anthracycline-induced cardiomyopathy: preliminary results of a prospective multicenter trial. Haematol Blood Transfus. 1990;33:566–70.PubMedGoogle Scholar
  113. 113.
    Milei J, Marantz A, Ale J, Vazquez A, Buceta JE. Prevention of adriamycin-induced cardiotoxicity by prenylamine: a pilot double blind study. Cancer Drug Deliv. 1987;4(2):129–36.PubMedGoogle Scholar
  114. 114.
    Kalay N, Basar E, Ozdogru I, Er O, Cetinkaya Y, Dogan A, et al. Protective effects of carvedilol against anthracycline-induced cardiomyopathy. J Am Coll Cardiol. 2006;48(11):2258–62.PubMedGoogle Scholar
  115. 115.
    Iarussi D, Auricchio U, Agretto A, Murano A, Giuliano M, Casale F, et al. Protective effect of coenzyme Q10 on anthracyclines cardiotoxicity: control study in children with acute lymphoblastic leukemia and non-Hodgkin lymphoma. Mol Aspects Med. 1994;15(Suppl):s207–12.PubMedGoogle Scholar
  116. 116.
    Waldner R, Laschan C, Lohninger A, Gessner M, Tuchler H, Huemer M, et al. Effects of doxorubicin-containing chemotherapy and a combination with l-carnitine on oxidative metabolism in patients with non-Hodgkin lymphoma. J Cancer Res Clin Oncol. 2006;132(2):121–8. doi: 10.1007/s00432-005-0054-8.PubMedGoogle Scholar
  117. 117.
    Smith LA, Cornelius VR, Plummer CJ, Levitt G, Verrill M, Canney P, 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. doi: 10.1186/1471-2407-10-337.PubMedPubMedCentralGoogle Scholar
  118. 118.
    Lowis S, Lewis I, Elsworth A, Weston C, Doz F, Vassal G, et al. A phase I study of intravenous liposomal daunorubicin (DaunoXome) in paediatric patients with relapsed or resistant solid tumours. Br J Cancer. 2006;95(5):571–80. doi: 10.1038/sj.bjc.6603288.PubMedPubMedCentralGoogle Scholar
  119. 119.
    Zerra P, Cochran TR, Franco VI, Lipshultz SE. An expert opinion on pharmacologic approaches to reducing the cardiotoxicity of childhood acute lymphoblastic leukemia therapies. Expert Opin Pharmacother. 2013;14(11):1497–513.PubMedGoogle Scholar
  120. 120.
    Cardinale D, Bacchiani G, Beggiato M, Colombo A, Cipolla CM. Strategies to prevent and treat cardiovascular risk in cancer patients. Semin Oncol. 2013;40(2):186–98. doi: 10.1053/j.seminoncol.2013.01.008.PubMedGoogle Scholar
  121. 121.
    Lipshultz SE, Lipsitz SR, Sallan SE, Simbre VC 2nd, Shaikh SL, Mone SM, et al. Long-term enalapril therapy for left ventricular dysfunction in doxorubicin-treated survivors of childhood cancer. J Clin Oncol. 2002;20(23):4517–22.PubMedGoogle Scholar
  122. 122.
    Ewer MS, Yeh ET. Cancer and the heart. Hamilton Lewiston: BC Decker Inc.; Distributed by BC Decker; 2006.Google Scholar
  123. 123.
    Pfeffer MA, Braunwald E, Moye LA, Basta L, Brown EJ Jr, Cuddy TE, et al. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. Results of the survival and ventricular enlargement trial. The SAVE Investigators. N Engl J Med. 1992;327(10):669–77. doi: 10.1056/NEJM199209033271001.PubMedGoogle Scholar
  124. 124.
    Sliwa K, Norton GR, Kone N, Candy G, Kachope J, Woodiwiss AJ, et al. Impact of initiating carvedilol before angiotensin-converting enzyme inhibitor therapy on cardiac function in newly diagnosed heart failure. J Am Coll Cardiol. 2004;44(9):1825–30. doi: 10.1016/j.jacc.2004.05.087.PubMedGoogle Scholar
  125. 125.
    Lipshultz SE, Adams MJ, Colan SD, Constine LS, Herman EH, Hsu DT, et al. Long-term cardiovascular toxicity in children, adolescents, and young adults who receive cancer therapy: pathophysiology, course, monitoring, management, prevention, and research directions: a scientific statement from the American Heart Association. Circulation. 2013;128(17):1927–95. doi: 10.1161/CIR.0b013e3182a88099.PubMedGoogle Scholar
  126. 126.
    Ward KM, Binns H, Chin C, Webber SA, Canter CE, Pahl E. Pediatric heart transplantation for anthracycline cardiomyopathy: cancer recurrence is rare. J Heart Lung Transplant. 2004;23(9):1040–5.PubMedGoogle Scholar
  127. 127.
    Lipshultz SE, Vlach SA, Lipsitz SR, Sallan SE, Schwartz ML, Colan SD. Cardiac changes associated with growth hormone therapy among children treated with anthracyclines. Pediatrics. 2005;115(6):1613–22.PubMedGoogle Scholar
  128. 128.
    Targeted Cancer Therapies. National Cancer Institute. Accessed 26 Nov 2013.
  129. 129.
    Mann DL. Targeted cancer therapeutics: the heartbreak of success. Nat Med. 2006;12(8):881–2. doi: 10.1038/nm0806-881.PubMedGoogle Scholar
  130. 130.
    Groarke JD, Cheng S, Moslehi J. Cancer-drug discovery and cardiovascular surveillance. N Engl J Med. 2013;369(19):1779–81. doi: 10.1056/NEJMp1313140.PubMedGoogle Scholar
  131. 131.
    Suttorp M, Millot F. Treatment of pediatric chronic myeloid leukemia in the year 2010: use of tyrosine kinase inhibitors and stem-cell transplantation. Hematology Am Soc Hematol Educ Program. 2010;2010:368–76. doi: 10.1182/asheducation-2010.1.368.PubMedGoogle Scholar
  132. 132.
    Oliansky DM, Camitta B, Gaynon P, Nieder ML, Parsons SK, Pulsipher MA, et al. The role of cytotoxic therapy with hematopoietic stem cell transplantation in the treatment of pediatric acute lymphoblastic leukemia: update of the 2005 evidence-based review. ASBMT Position Statement. Biol Blood Marrow Transpl. 2012;18(7):979–81. doi: 10.1016/j.bbmt.2012.03.011.Google Scholar
  133. 133.
    Oliansky DM, Larson RA, Weisdorf D, Dillon H, Ratko TA, Wall D, et al. The role of cytotoxic therapy with hematopoietic stem cell transplantation in the treatment of adult acute lymphoblastic leukemia: update of the 2006 evidence-based review. Biol Blood Marrow Transpl. 2012;18(1):16–7. doi: 10.1016/j.bbmt.2011.09.002.Google Scholar
  134. 134.
    Kerkela R, Grazette L, Yacobi R, Iliescu C, Patten R, Beahm C, et al. Cardiotoxicity of the cancer therapeutic agent imatinib mesylate. Nat Med. 2006;12(8):908–16. doi: 10.1038/nm1446.PubMedGoogle Scholar
  135. 135.
    Atallah E, Durand JB, Kantarjian H, Cortes J. Congestive heart failure is a rare event in patients receiving imatinib therapy. Blood. 2007;110(4):1233–7. doi: 10.1182/blood-2007-01-070144.PubMedGoogle Scholar
  136. 136.
    Bond M, Bernstein ML, Pappo A, Schultz KR, Krailo M, Blaney SM, et al. A phase II study of imatinib mesylate in children with refractory or relapsed solid tumors: a Children’s Oncology Group study. Pediatr Blood Cancer. 2008;50(2):254–8. doi: 10.1002/pbc.21132.PubMedGoogle Scholar
  137. 137.
    Schultz KR, Bowman WP, Aledo A, Slayton WB, Sather H, Devidas M, et al. Improved early event-free survival with imatinib in Philadelphia chromosome-positive acute lymphoblastic leukemia: a children’s oncology group study. J Clin Oncol. 2009;27(31):5175–81. doi: 10.1200/JCO.2008.21.2514.PubMedPubMedCentralGoogle Scholar
  138. 138.
    Pavey T, Hoyle M, Ciani O, Crathorne L, Jones-Hughes T, Cooper C et al. Dasatinib, nilotinib and standard-dose imatinib for the first-line treatment of chronic myeloid leukaemia: systematic reviews and economic analyses. Health Technol Assess. 2012;16(42):iii–iv, 1–277. doi: 10.3310/hta16420.
  139. 139.
    FDA Drug Safety Communication: FDA asks manufacturer of the leukemia drug Iclusig (ponatinib) to suspend marketing and sales. U.S. Food and Drug Administration. 2013. Accessed 26 Nov 2013.
  140. 140.
    Tefferi A. Nilotinib treatment-associated accelerated atherosclerosis: when is the risk justified? Leukemia. 2013;27(9):1939–40. doi: 10.1038/leu.2013.112.PubMedPubMedCentralGoogle Scholar
  141. 141.
    Hudis CA. Trastuzumab-mechanism of action and use in clinical practice. N Engl J Med. 2007;357(1):39–51. doi: 10.1056/NEJMra043186.PubMedGoogle Scholar
  142. 142.
    De Keulenaer GW, Doggen K, Lemmens K. The vulnerability of the heart as a pluricellular paracrine organ: lessons from unexpected triggers of heart failure in targeted ErbB2 anticancer therapy. Circ Res. 2010;106(1):35–46. doi: 10.1161/CIRCRESAHA.109.205906.PubMedGoogle Scholar
  143. 143.
    Bowles EJ, Wellman R, Feigelson HS, Onitilo AA, Freedman AN, Delate T, et al. Risk of heart failure in breast cancer patients after anthracycline and trastuzumab treatment: a retrospective cohort study. J Natl Cancer Inst. 2012;104(17):1293–305. doi: 10.1093/jnci/djs317.PubMedPubMedCentralGoogle Scholar
  144. 144.
    Ewer MS, Vooletich MT, Durand JB, Woods ML, Davis JR, Valero V, et al. Reversibility of trastuzumab-related cardiotoxicity: new insights based on clinical course and response to medical treatment. J Clin Oncol. 2005;23(31):7820–6. doi: 10.1200/JCO.2005.13.300.PubMedGoogle Scholar
  145. 145.
    Perez EA, Koehler M, Byrne J, Preston AJ, Rappold E, Ewer MS. Cardiac safety of lapatinib: pooled analysis of 3689 patients enrolled in clinical trials. Mayo Clin Proc. 2008;83(6):679–86. doi: 10.4065/83.6.679.PubMedGoogle Scholar
  146. 146.
    Albanell J, Montagut C, Jones ET, Pronk L, Mellado B, Beech J, et al. A phase I study of the safety and pharmacokinetics of the combination of pertuzumab (rhuMab 2C4) and capecitabine in patients with advanced solid tumors. Clin Cancer Res. 2008;14(9):2726–31. doi: 10.1158/1078-0432.CCR-07-1980.PubMedGoogle Scholar
  147. 147.
    Fouladi M, Stewart CF, Blaney SM, Onar-Thomas A, Schaiquevich P, Packer RJ, et al. Phase I trial of lapatinib in children with refractory CNS malignancies: a Pediatric Brain Tumor Consortium study. J Clin Oncol. 2010;28(27):4221–7. doi: 10.1200/JCO.2010.28.4687.PubMedPubMedCentralGoogle Scholar
  148. 148.
    Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004;350(23):2335–42. doi: 10.1056/NEJMoa032691.PubMedGoogle Scholar
  149. 149.
    Bair SM, Choueiri TK, Moslehi J. Cardiovascular complications associated with novel angiogenesis inhibitors: emerging evidence and evolving perspectives. Trends Cardiovasc Med. 2013;23(4):104–13. doi: 10.1016/j.tcm.2012.09.008.PubMedPubMedCentralGoogle Scholar
  150. 150.
    Sekeres MA. The avastin story. N Engl J Med. 2011;365(15):1454–5. doi: 10.1056/NEJMc1109550.PubMedGoogle Scholar
  151. 151.
    Ranpura V, Hapani S, Chuang J, Wu S. Risk of cardiac ischemia and arterial thromboembolic events with the angiogenesis inhibitor bevacizumab in cancer patients: a meta-analysis of randomized controlled trials. Acta Oncol. 2010;49(3):287–97. doi: 10.3109/02841860903524396.PubMedGoogle Scholar
  152. 152.
    Omuro A, DeAngelis LM. Glioblastoma and other malignant gliomas: a clinical review. JAMA. 2013;310(17):1842–50. doi: 10.1001/jama.2013.280319.PubMedGoogle Scholar
  153. 153.
    MacDonald TJ, Aguilera D, Kramm CM. Treatment of high-grade glioma in children and adolescents. Neuro Oncol. 2011;13(10):1049–58. doi: 10.1093/neuonc/nor092.PubMedPubMedCentralGoogle Scholar
  154. 154.
    Darlow BA, Ells AL, Gilbert CE, Gole GA, Quinn GE. Are we there yet? Bevacizumab therapy for retinopathy of prematurity. Arch Dis Child Fetal Neonatal Ed. 2013;98(2):F170–4. doi: 10.1136/archdischild-2011-301148.PubMedGoogle Scholar
  155. 155.
    Dubois SG, Shusterman S, Ingle AM, Ahern CH, Reid JM, Wu B, et al. Phase I and pharmacokinetic study of sunitinib in pediatric patients with refractory solid tumors: a children’s oncology group study. Clin Cancer Res. 2011;17(15):5113–22. doi: 10.1158/1078-0432.CCR-11-0237.PubMedPubMedCentralGoogle Scholar
  156. 156.
    Inaba H, Rubnitz JE, Coustan-Smith E, Li L, Furmanski BD, Mascara GP, et al. Phase I pharmacokinetic and pharmacodynamic study of the multikinase inhibitor sorafenib in combination with clofarabine and cytarabine in pediatric relapsed/refractory leukemia. J Clin Oncol. 2011;29(24):3293–300. doi: 10.1200/JCO.2011.34.7427.PubMedPubMedCentralGoogle Scholar
  157. 157.
    Widemann BC, Kim A, Fox E, Baruchel S, Adamson PC, Ingle AM, et al. A phase I trial and pharmacokinetic study of sorafenib in children with refractory solid tumors or leukemias: a Children’s Oncology Group Phase I Consortium report. Clin Cancer Res. 2012;18(21):6011–22. doi: 10.1158/1078-0432.CCR-11-3284.PubMedPubMedCentralGoogle Scholar
  158. 158.
    Chu TF, Rupnick MA, Kerkela R, Dallabrida SM, Zurakowski D, Nguyen L, et al. Cardiotoxicity associated with tyrosine kinase inhibitor sunitinib. Lancet. 2007;370(9604):2011–9. doi: 10.1016/S0140-6736(07)61865-0.PubMedPubMedCentralGoogle Scholar
  159. 159.
    Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359(4):378–90. doi: 10.1056/NEJMoa0708857.PubMedGoogle Scholar
  160. 160.
    Schmidinger M, Zielinski CC, Vogl UM, Bojic A, Bojic M, Schukro C, et al. Cardiac toxicity of sunitinib and sorafenib in patients with metastatic renal cell carcinoma. J Clin Oncol. 2008;26(32):5204–12. doi: 10.1200/JCO.2007.15.6331.PubMedGoogle Scholar
  161. 161.
    Telli ML, Witteles RM, Fisher GA, Srinivas S. Cardiotoxicity associated with the cancer therapeutic agent sunitinib malate. Ann Oncol. 2008;19(9):1613–8. doi: 10.1093/annonc/mdn168.PubMedGoogle Scholar
  162. 162.
    Rini BI, Cohen DP, Lu DR, Chen I, Hariharan S, Gore ME, et al. Hypertension as a biomarker of efficacy in patients with metastatic renal cell carcinoma treated with sunitinib. J Natl Cancer Inst. 2011;103(9):763–73. doi: 10.1093/jnci/djr128.PubMedPubMedCentralGoogle Scholar
  163. 163.
    Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Siebels M, et al. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med. 2007;356(2):125–34. doi: 10.1056/NEJMoa060655.PubMedGoogle Scholar
  164. 164.
    Paoletti X, Geoerger B, Doz F, Baruchel A, Lokiec F, Le Tourneau C. A comparative analysis of paediatric dose-finding trials of molecularly targeted agent with adults’ trials. Eur J Cancer. 2013;49(10):2392–402. doi: 10.1016/j.ejca.2013.02.028.PubMedGoogle Scholar
  165. 165.
    Adverse Events/CTCAE. National Cancer Institute. 2013. Accessed 26 Nov 2013.
  166. 166.
    Lipshultz SE. Ventricular dysfunction clinical research in infants, children and adolescents. Prog Pediatr Cardiol. 2000;12(1):1–28. doi: 10.1016/S1058-9813(00)00076-X.PubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  • Steven E. Lipshultz
    • 2
  • Melissa B. Diamond
    • 1
  • Vivian I. Franco
    • 2
  • Sanjeev Aggarwal
    • 3
  • Kasey Leger
    • 4
  • Maria Verônica Santos
    • 5
  • Stephen E. Sallan
    • 6
  • Eric J. Chow
    • 7
  1. 1.Division of Pediatric Cardiology, Department of PediatricsUniversity of Miami Miller School of MedicineMiamiUSA
  2. 2.Department of PediatricsWayne State University School of Medicine and the Children’s Research Center of Michigan at the Children’s Hospital of MichiganDetroitUSA
  3. 3.Division of Pediatric Cardiology, Department of PediatricsWayne State University School of Medicine and the Children’s Hospital of MichiganDetroitUSA
  4. 4.Department of Pediatric Hematology-OncologyUniversity of Texas Southwestern Medical CenterDallasUSA
  5. 5.Department of Cardiology and Pediatric Oncology, Instituto de Oncologia Pediátrica/GRAACCFederal University of São Paolo UNIFESPSão PauloBrazil
  6. 6.Division of Pediatric Oncology, Department of PediatricsHarvard Medical School and Boston Children’s Hospital, Dana-Farber Cancer InstituteBostonUSA
  7. 7.Department of Pediatrics, Seattle Children’s Hospital, Fred Hutchinson Cancer Research CenterUniversity of WashingtonSeattleUSA

Personalised recommendations