Review

Cardiotoxicity in childhood cancer survivors: strategies for prevention and management

Danielle Harake

Department of Pediatrics, University of Miami Miller School of Medicine, Miami, FL, USA

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Vivian I Franco

Department of Pediatrics, University of Miami Miller School of Medicine, Miami, FL, USA

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Jacqueline M Henkel

Department of Pediatrics, University of Miami Miller School of Medicine, Miami, FL, USA

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Tracie L Miller

Department of Pediatrics, University of Miami Miller School of Medicine, Miami, FL, USA

Holtz Children’s Hospital of the University of Miami/Jackson Memorial Medical Center; Sylvester Comprehensive Cancer Center, Miami, FL, USA

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Steven E Lipshultz

* Author for correspondence

Department of Pediatrics, University of Miami Miller School of Medicine, Miami, FL, USA.

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Email the corresponding author at slipshultz@med.miami.edu

Published Online:7 Aug 2012https://doi.org/10.2217/fca.12.44

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Abstract

Advances in cancer treatment have greatly improved survival rates of children with cancer. However, these same chemotherapeutic or radiologic treatments may result in long-term health consequences. Anthracyclines, chemotherapeutic drugs commonly used to treat children with cancer, are known to be cardiotoxic, but the mechanism by which they induce cardiac damage is still not fully understood. A higher cumulative anthracycline dose and a younger age of diagnosis are only a few of the many risk factors that identify the children at increased risk of developing cardiotoxicity. While cardiotoxicity can develop at anytime, starting from treatment initiation and well into adulthood, identifying the best cardioprotective measures to minimize the long-term damage caused by anthracyclines in children is imperative. Dexrazoxane is the only known agent to date, that is associated with less cardiac dysfunction, without reducing the oncologic efficacy of the anthracycline doxorubicin in children. Given the serious long-term health consequences of cancer treatments on survivors of childhood cancers, it is essential to investigate new approaches to improving the safety of cancer treatments.

Keywords:

Papers of special note have been highlighted as: ▪ of interest ▪▪ of considerable interest

References

1 Mariotto AB, Rowland JH, Yabroff KR et al. Long-term survivors of childhood cancers in the United States. Cancer Epidemiol. Biomarkers Prev.18,1033–1040 (2009).Crossref, Medline, Google Scholar
2 Hinkle AS, Proukou C, French CA et al. A clinic-based, comprehensive care model for studying late effects in long-term survivors of pediatric illnesses. Pediatrics113(Suppl. 4),1141–1145 (2004).Medline, Google Scholar
3 Reulen RC, Winter DL, Frobisher C et al. Long-term cause-specific mortality among survivors of childhood cancer. JAMA304(2),172–179 (2010).Crossref, Medline, CAS, Google Scholar
4 Mulrooney DA, Yeazel MW, Kawashima T et al. Cardiac outcomes in a cohort of adult survivors of childhood and adolescent cancer: retrospective analysis of the Childhood Cancer Survivor study cohort. BMJ339,b4606 (2009).Crossref, Medline, Google Scholar
5 van der Pal HJ, van Dalen EC, van Delden E et al. High risk of symptomatic cardiac events in childhood cancer survivors. J. Clin. Oncol.30(13),1429–1437 (2012).Crossref, Medline, Google Scholar
6 Lipshultz SE, Adams MJ. Cardiotoxicity after childhood cancer: beginning with the end in mind. J. Clin. Oncol.28(8),1276–1281 (2010).▪▪ Critically analyzes various aspects of the association between specific treatments and specific cardiovascular causes of death in childhood cancer treatment. It raises several critical questions in determining which screening modalities could be most useful.Crossref, Medline, Google Scholar
7 Hudson MM, Mertens AC, Yasui Y et al. Health status of adult long-term survivors of childhood cancer: a report from the childhood cancer survivor study. JAMA290(12),1583–1592 (2003).Crossref, Medline, CAS, Google Scholar
8 Mody R, Li S, Dover DC et al. Twenty-five-year follow-up among survivors of childhood acute lymphoblastic leukemia: a report from the Childhood Cancer Survivor study. Blood111(12),5515–5523 (2008).Crossref, Medline, CAS, Google Scholar
9 Miller TL, Lipsitz SR, Lopez-Mitnik G et al. Characteristics and determinants of adiposity in pediatric cancer survivors. Cancer Epidemiol. Biomarkers Prev.19(8),2013–2022 (2010).▪ Determined that emerging long-term complications of childhood cancer survivors, such as adiposity, should be closely monitored.Crossref, Medline, Google Scholar
10 National Research Council. Chapter 4: late effects of childhood cancer. In: Childhood Cancer Survivorship: Improving Care and Quality of Life. Hewitt M, Weiner SL, Simone JV (Eds). National Academic Press, DC, USA, 48–49 (2003).Google Scholar
11 Alvarez JA, Scully RE, Miller TL et al. Long-term effects of treatments for childhood cancers. Curr. Opin. Pediatr.19,23–31 (2007).Crossref, Medline, Google Scholar
12 van Dalen EC, Raphaël MF, Caron HN, Kremer LC. Treatment including anthracyclines versus treatment not including anthracyclines for childhood cancer. Cochrane Database Syst. Rev.1,CD006647 (2009).Google Scholar
13 Fulbright JM, Huh W, Anderson P, Chandra J. Can anthracycline therapy for pediatric malignancies be less cardiotoxic? Curr. Oncol. Rep.12(6),411–419 (2010).Crossref, Medline, Google Scholar
14 Herman EH, Ferrans VJ, Jordan W, Ardalan B. Reduction of chronic daunorubicin cardiotoxicity by ICRF-187 in rabbits. Res. Commun. Chem. Pathol. Pharmacol.31(1),85–97 (1981).Medline, CAS, Google Scholar
15 Herman EH, el-Hage AN, Ferrans VJ, Ardalan B. Comparison of the severity of the chronic cardiotoxicity produced by doxorubicin in normotensive and hypertensive rats. Toxicol. Appl. Pharmacol.78(2),202–214 (1985).Crossref, Medline, CAS, Google Scholar
16 Outomuro D, Grana DR, Azzato F, Milei J. Adriamycin-induced myocardial toxicity: new solutions for an old problem? Int. J. Cardiol.117(1),6–15 (2007).Crossref, Medline, Google Scholar
17 Mordente A, Meucci E, Martorana GE, Giardina B, Minotti G. Human heart cytosolic reductases and anthracycline cardiotoxicity. IUBMB Life52,83–88 (2001).Crossref, Medline, CAS, Google Scholar
18 Wouters KA, Kremer LC, Miller TL, Herman EH, Lipshultz SE. Protecting against anthracycline-induced myocardial damage: a review of the most promising strategies. Br. J. Haematol.131(5),561–578 (2005).Crossref, Medline, CAS, Google Scholar
19 Gianni L, Zweier JL, Levy A, Myers CE. Characterization of the cycle of iron-mediated electron transfer from adriamycin to molecular oxygen. J. Biol. Chem.260(11),6820–6826 (1985).Crossref, Medline, CAS, Google Scholar
20 Olson RD, Mushlin PS. Doxorubicin cardiotoxicity: analysis of prevailing hypothesis. FASEB J.4(13),3076–3086 (1990).Crossref, Medline, CAS, Google Scholar
21 Milei J, Boveris A, Llesuy S et al. Amelioration of adriamycin-induced cardiotoxicity in rabbits by prenylamine and vitamins A and E. Am. Heart J.111,95–102 (1986).Crossref, Medline, CAS, Google Scholar
22 Ferrero ME, Ferrero E, Gaja U. Adriamycin: energy metabolism and mitochondrial oxidations in the heart of treated rabbits. Biochem. Pharmacol.25(2),125–130 (1976).Crossref, Medline, CAS, Google Scholar
23 Earm YE, Ho WK, So I. Effects of adriamycin on ionic currents in single cardiac myocytes of the rabbit. J. Mol. Cell. Cardiol.26(2),163–172 (1994).Crossref, Medline, CAS, Google Scholar
24 Olson RD, Li X, Palade P et al. Sarcoplasmic reticulum calcium release is stimulated and inhibited by daunorubicin and daunorubicinol. Toxicol. Appl. Pharmacol.169(2),168–176 (2000).Crossref, Medline, CAS, Google Scholar
25 Gozalvez M, Blanco M. Inhibition of NA-K ATPase by the antitumor antibiotic adriamycin. 5th International Biophysics Congress, Copenhagen. Cancer Res.39(1),257–261 (1979).Medline, Google Scholar
26 Lou H, Danelisen I, Singal PK. Cytokines are not upregulated in adriamycin-induced cardiomyopathy and heart failure. J. Mol. Cell. Cardiol.36(5),683–690 (2004).Crossref, Medline, CAS, Google Scholar
27 Lenaz L, Page JA. Cardiotoxicity of adriamycin and related anthracyclines. Cancer Treat. Rev.3(3),111–120 (1976).Crossref, Medline, CAS, Google Scholar
28 Lipshultz SE, Rusconi P, Scully RE. Chapter 18: assessment of cardiotoxicity during anti-cancer therapy. In: NT-proBNP as a Biomarker in Cardiovascular Diseases. Januzzi JL, Bayes-Genis A (Eds). Prous Science SA, Barcelona, Spain, 193–198 (2007).Google Scholar
29 Pointon AV, Walker TM, Phillips KM et al. Doxorubicin in vivo rapidly alters expression and translation of myocardial electron transport chain genes, leads to ATP loss and caspase 3 activation. PLoS ONE5(9),e12733 (2010).Crossref, Medline, Google Scholar
30 Gonzalvez F, Gottlieb E. Cardiolipin: setting the beat of apoptosis. Apoptosis12(5),877–885 (2007).Crossref, Medline, CAS, Google Scholar
31 Goormaghtigh E, Brasseur R, Huart P, Ruysschaert JM. Study of the adriamycin cardiolipin complex structure using attenuated total reflection infrared spectroscopy. Biochemistry26(6),1789–1794 (1987).Crossref, Medline, CAS, Google Scholar
32 Garcia Fernandez M, Troiano L, Moretti L. Early changes in intramitochondrial cardiolipin distribution during apoptosis. Cell Growth Differ.13(9),449–455 (2002).Medline, Google Scholar
33 Aguilar L, Ortega-Pierres G, Campos B et al. Phospholipid membranes form specific nonbilayer molecular arrangements that are antigenic. J. Biol. Chem.274(36),25193–25196 (1999).Crossref, Medline, CAS, Google Scholar
34 Vlasova II, Tyurin VA, Kapralov AA et al. Nitric oxide inhibits peroxidase activity of cytochrome C cardiolipin complex and blocks cardioliopin oxidation. J. Biol. Chem.281(21),14554–14562 (2006).Crossref, Medline, CAS, Google Scholar
35 Arola OJ, Saraste A, Pulkki K, Kallajoki M, Parvinen M, Voipio-Pulkki LM. Acute doxorubicin cardiotoxicity involves cardiomyocte apoptosis. Cancer Res.60(7),1789–1792 (2000).Medline, CAS, Google Scholar
36 Zhang YQ, Shi J, Li YJ, Wei L. Cardiomyocyte death in doxorubicin-induced cardiotoxicity. Arch. Immunol. Ther. Exp.57(6),435–445 (2009).Crossref, Medline, CAS, Google Scholar
37 Adams MJ, Lipshultz SE. Pathophysiology of anthracycline- and radiation-associated cardiomyopathies: implications for screening and prevention. Pediatr. Blood Cancer44(7),600–606 (2005).Crossref, Medline, Google Scholar
38 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.324(12),808–815 (1991).▪ Established that that doxorubicin impairs myocardial growth resulting in reduced contractility in a dose-dependent manner.Crossref, Medline, CAS, Google Scholar
39 Sorensen K, Levitt G, Bull C, Chessells J, Sullivan I. Anthracycline dose in childhood acute lymphoblastic leukemia: issues of early survival versus late cardiotoxicity. J. Clin. Oncol.15(1),61–68 (1997).Crossref, Medline, CAS, Google Scholar
40 Giantris A, Abdurrahman L, Hinkle A et al. Anthracycline-induced cardiotoxicity in children and young adults. Crit. Rev. Oncol. Hematol.27,53–68 (1998).Crossref, Medline, CAS, Google Scholar
41 Doroshow JH, Locker GY, Myers CE. Enzymatic defenses of the mouse heart against reactive oxygen metabolites: alterations produced by doxorubicin. J. Clin. Invest.65(1),128–135 (1980).Crossref, Medline, CAS, Google Scholar
42 Cascales A, Sanchez-Vega B, Navarro N, Pastor-Quirante F, Corral J, Vicente V, de la Pena FA. Clinical and genetic determinants of anthracycline-induced cardiac iron accumulation. Int. J. Cardiol.154(3),282–286 (2010).Crossref, Medline, Google Scholar
43 Arai M, Yoguchi A, Takizawa T et al. Mechanism of doxorubicin-induced inhibition of sarcoplasmic reticulum Ca²⁺-ATPase gene transcription. Circ. Res.86(1),8–14 (2000).Crossref, Medline, CAS, Google Scholar
44 Jeyaseelan R, Poizat C, Wu HY, Kedes L. Molecular mechanisms of doxorubicin-induced cardiomyopathy. Selective suppression of Reiske iron-sulfur protein, ADP/ATP translocase, and phosphofructokinase genes is associated with ATP depletion in rat cardiomyocytes. J. Biol. Chem.272(9),5828–5832 (1997).Crossref, Medline, CAS, Google Scholar
45 Lebrecht DMS, Setzer B, Ketelsen UP, Haberstroh J, Walker UA. Time-dependant and tissue-specific accumulation of mtDNA and respiratory chain defects in chronic doxorubicin cardiomyopathy. Circulation108(19),2423–2429 (2003).Crossref, Medline, CAS, Google Scholar
46 Arola OJ, Saraste A, Pulkki K, Kallajoki M, Parvinen M, Voipio-Pulkki LM. Acute doxorubicin cardiotoxicity involves cardiomyocte apoptosis. Cancer Res.60(7),1789–1792 (2000).Medline, CAS, Google Scholar
47 Childs AC, Phaneuf SL, Dirks AJ, Phillips T, Leeuwenburgh C. Doxorubicin treatment in vivo causes cytochrome C release and cardiomyocyte apoptosis, as well as increased mitochondrial efficiency, superoxide dismutase activity, and Bcl-2:Bax ratio. Cancer Res.62(16),4592–4598 (2002).Medline, CAS, Google Scholar
48 Von Hoff DD, Layard M, Basa P et al. Risk factors for doxorubicin-induced congestive heart failure. Ann. Intern. Med.91(5),710–717 (1979).Crossref, Medline, CAS, Google Scholar
49 Swain SM, Whaley FS, Ewer MS. Congestive heart failure in patients treated with doxorubicin: a retrospective analysis of three trials. Cancer97(11),2869–2879 (2003).Crossref, Medline, CAS, Google Scholar
50 van Dalen EC, van der Pal HJ, Kok WE, Caron HN, Kremer LC. Clinical heart failure in a cohort of children treated with anthracyclines: a long-term follow-up study. Eur. J. Cancer42(18),3191–3198 (2006).Crossref, Medline, CAS, Google Scholar
51 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.170(14),1247–1255 (2010).Crossref, Medline, CAS, Google Scholar
52 Blanco JG, Sun CL, Landier 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.30(13),1415–1421 (2012).Crossref, Medline, CAS, Google Scholar
53 van Dalen EC, Caron HN, Dickinson HO, Kremer LCM. Cardioprotective interventions for cancer patients receiving anthracyclines. Cochrane Database Syst. Rev.25(1),CD003917. Update in: Cochrane Database Syst. Rev.2011(6),CD003917 (2005).Google Scholar
54 Lipshultz SE, Lipsitz SR, Sallen SE et al. Chronic progressive cardiac dysfunction years after doxorubicin therapy for childhood acute lymphoblastic leukemia. J. Clin. Oncol.23(12),2629–2636 (2005).▪▪ Cardiac dysfunction can be persistent and progressive in childhood survivors of acute lymphoblastic leukemia. Dilated cardiomyopathy can develop in these children after treatment; however, this study also found that as time passed the children expressed a restrictive cardiomyopathy pattern in their measurements.Crossref, Medline, CAS, Google Scholar
55 Davies SM. Getting to the heart of the matter. J. Clin. Oncol.30(13),1399–1400 (2012).Crossref, Medline, Google Scholar
56 Visscher H, Ross CJD, Rassekh SR et al. Pharmacogenomic prediction of anthracycline-induced cardiotoxicity in children. J. Clin. Oncol.30(13),1422–1428 (2012).Crossref, Medline, Google Scholar
57 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.15,1544–1552 (1997).Crossref, Medline, CAS, Google Scholar
58 Sorensen K, Levitt GA, Bull C, Dorup I, Sullivan ID. Late anthracycline cardiotoxicity after childhood cancer: a prospective longitudinal study. Cancer97(8),1991–1998 (2003).Crossref, Medline, CAS, Google Scholar
59 Nysom K, Holm K, Lipsitz SR et al. Relationship between cumulative anthracycline dose and late cardiotoxicity in childhood acute lymphoblastic leukemia. J. Clin. Oncol.2,545–550 (1998).Crossref, Google Scholar
60 Lipshultz SE, Lipsitz SR, Mone SM et al. Female sex and higher drug dose as risk factors for late cardiotoxic effects of doxorubicin therapy for childhood cancer. N. Engl. J. Med.332(26),1738–1743 (1995).Crossref, Medline, CAS, Google Scholar
61 Steinherz LJ, Steinherz PG, Tan CT, Heller G, Murphy ML. Cardiac toxicity 4 to 20 years after completing anthracycline therapy. JAMA266(12),1672–1677 (1991).Crossref, Medline, CAS, Google Scholar
62 Anderlini P, Bengamin RS, Wong FC et al. Idarubicin cardiotoxicity: a retrospective study in acute myeloid leukemia and myelodysplasia. J. Clin. Oncol.13(11),2827–2834 (1995).Crossref, Medline, CAS, Google Scholar
63 Sorensen K, Levitt G, Sebag-Montefiore D, Bull C, Sullivan I. Cardiac function in Wilms’ tumor survivors. J. Clin. Oncol.13(7),1546–1556 (1995).Crossref, Medline, CAS, Google Scholar
64 Nysom K, Colan DC, Lipshultz SE. Late cardiotoxicity following anthracycline therapy for childhood cancer. Prog. Pediatr. Cardiol.8,121–138 (1998).Crossref, Google Scholar
65 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.19(7),1926–1934 (2001).Crossref, Medline, CAS, Google Scholar
66 Kremer LCM, van Dalen EC, Offringa M, Ottenkamp J, Voûte PA. Anthracycline-induced clinical heart failure in a cohort of 607 children: long-term follow-up study. J. Clin. Oncol.19(1),191–196 (2001).Crossref, Medline, CAS, Google Scholar
67 Tukenova M, Guibout C, Oberlin O et al. Role of cancer treatment in long-term overall and cardiovascular mortality after childhood cancer. J. Clin. Oncol.28(8),1308–1315 (2010).Crossref, Medline, Google Scholar
68 Rodvold KA, Rushing DA, Tewksbury DA. Doxorubicin clearance in the obese. J. Clin. Oncol.6(8),1321–1327 (1998).Crossref, Google Scholar
69 Bristow MR, Thompson PD, Martin RP, Mason JW, Billingham ME, Harrison DC. Early anthracycline cardiotoxicity. Am. J. Med.65(5),823–832 (1978).Crossref, Medline, CAS, Google Scholar
70 Lipshultz SE, Miller TM, 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.30(10),1042–1049 (2012).▪▪ Early detection of damage or death to the cardiomyocytes is crucial to individualization of treatment and effective prevention. This study found that cardiac troponin T and N-terminal probrain natriuretic peptide hold promise as biomarkers of cardiotoxicity for children with high-risk acute lymphoblastic leukemia.Crossref, Medline, CAS, Google Scholar
71 Ali MK, Ewer MS, Gibbs HR, Swafford J, Graff KL. Late doxorubicin-associated cardiotoxicity in children. The possible role of intercurrent viral infection. Cancer74(1),182–188 (1994).Crossref, Medline, CAS, Google Scholar
72 Tolba KA, Deliargyris EN. Cardiotoxicity of cancer therapy. Cancer Invest.17(6),408–422 (1999).Crossref, Medline, CAS, Google Scholar
73 Lipshultz SE, Alvarez JA, Scully RE. Anthracycline associated cardiotoxicity in survivors of childhood cancer. Heart94(4),525–533 (2008).Crossref, Medline, CAS, Google Scholar
74 Grenier MA, Lipshultz ME. Epidemiology of anthracycline cardiotoxicity in children and adults. Semin. Oncol.25(4 Suppl. 10),72–85 (1998).Medline, CAS, Google Scholar
75 Simbre VC, Duffy SA, Dadlani GH, Miller TL, Lipshultz SE. Cardiotoxicity of cancer chemotherapy: implications for children. Paediatr. Drugs7,187–202 (2005).Crossref, Medline, Google Scholar
76 Barry E, Alvarez JA, Scully RE, Miller TL, Lipshultz SE. Anthracycline-induced cardiotoxicity: course, pathophysiology, prevention and management. Expert Opin. Pharmacother.8,1039–1058 (2007).Crossref, Medline, CAS, Google Scholar
77 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.17,2237–2243 (1999).Crossref, Medline, CAS, Google Scholar
78 Lipshultz SE, Sanders SP, Goorin AM, Krischer JP, Sallan SE, Colan SD. Monitoring for anthracycline cardiotoxicity. Pediatrics93,433–437 (1994).Medline, CAS, Google Scholar
79 Carver JR, Shapiro CL, NG A et al. ASCO Cancer Survivorship Exert Panel. American Society of Clinical Oncology clinical evidence review on the ongoing care of adult cancer survivors: cardiac and pulmonary late effects. J. Clin. Oncol.25,3991–4008 (2007).Crossref, Medline, CAS, Google Scholar
80 Steinhertz 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 Children’s Cancer Study Group. Pediatrics89,942–949 (1992).Medline, Google Scholar
81 Lipshultz SE, Sanders SP, Colan SD, Goorin AM, Sallan SE, Krischer JP. Letter to the Editor. Pediatrics94,781 (1994)Google Scholar
82 Adams MJ, Lipshultz SE, Schwartz C, Fajardo LF, Coen V, Constine LS. Radiation-associated cardiovascular disease: manifestations and management. Semin. Radiat. Oncol.13(3),346–356 (2003).Crossref, Medline, Google Scholar
83 Adams MJ, Hardenbergh PH, Constine LS, Lipshultz SE. Radiation-associated cardiovascular disease. Crit. Rev. Oncol. Hematol.45(1),55–75 (2003).Crossref, Medline, Google Scholar
84 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.351(2),145–153 (2004).Crossref, Medline, CAS, Google Scholar
85 Ganame J, Claus P, Eyskens B et al. Acute cardiac functional and morphological changes after anthracycline infusions in children. Am. J. Cardiol.99(7),974–977 (2007).Crossref, Medline, CAS, Google Scholar
86 Ganame J, Claus P, Uyttebroeck A et al. Myocardial dysfunction late after low-dose anthracycline treatment in asymptomatic pediatric patients. J. Am. Soc. Echocardiogr.20(12),1351–1358 (2007).Crossref, Medline, Google Scholar
87 Colan SD, Borrow KM, Neuman A. Left ventricular end-systolic wall stress-velocity of fiber shortening relation: a load independent index of myocardial contractility. J. Am. Coll. Cardiol.4,715–724 (1984).Crossref, Medline, CAS, Google Scholar
88 Lipshultz SE, Colan SD. The use of echocardiography and holter monitoring in the assessment of anthracycline-treated patients. In: Cardiac Toxicity After Treatment for Childhood Cancer. Wiley-Liss, NY, USA, 45–62 (1993).Google Scholar
89 Mitani I, Jain D, Joska TM, Burtness B, Zaret BL. Doxorubicin cardiotoxicity: Prevention of congestive heart failure with serial cardiac function monitoring with equilibrium radionuclide angiocardiography in the current era. J. Nucl. Cardiol.10(2),132–139 (2003).Crossref, Medline, Google Scholar
90 Glanzmann C, Huguenin P, Lutolf UM, Maire R, Jenni R, Gumppenberg V. Cardiac lesions after mediastinal radiation for Hodgkin’s disease. Radiother. Oncol.30(1),43–54 (1994).Crossref, Medline, CAS, Google Scholar
91 Lipshultz SE, Rifai N, Sallan SE et al. Predictive value of cardiac troponin T in pediatric patients at risk for myocardial injury. Circulation96(8),2641–2648 (1997).Crossref, Medline, CAS, Google Scholar
92 Levin ER, Gardner DG, Samson WK. Natriuretic peptides. N. Engl. J. Med.339(5),321–328 (1998).Crossref, Medline, CAS, Google Scholar
93 Cowie MR, Mendez GF. BNP and congestive heart failure. Prog. Cardiovasc. Dis.44(4),293–321 (2002).Crossref, Medline, CAS, Google Scholar
94 Linssen GC, Bakker SJ, Voors AA et al. N-terminal pro-B-type natriuretic peptide is an independent predictor of cardiovascular morbidity and mortality in the general population. Eur. Heart J.31(1),120–127 (2010).Crossref, Medline, CAS, Google Scholar
95 Bibbins-Domingo K, Gupta R, Na B et al. N-terminal fragment of the prohormone brain-type natriuretic peptide (NT-proBNP), cardiovascular events, and mortality in patients with stable coronary heart disease. JAMA297,169–176 (2007).Crossref, Medline, CAS, Google Scholar
96 Trachtenberg BH, Landy DC, Franco VI et al. Anthracycline-associated cardiotoxicity in survivors of childhood cancer. Pediatr. Cardiol.32,342–353 (2011).Crossref, Medline, Google Scholar
97 Franco VI, Henkel JM, Miller TL, Lipshultz SE. Cardiovascular effects in childhood cancer survivors treated with anthracyclines. Cardiol. Res. Pract.10,134679 (2011).Google Scholar
98 Schwartz CL, Hobbie WL, Truesdell S, Constine LC, Clark EB. Corrected QT interval prolongation in anthracycline-treated survivors of childhood cancer. J. Clin. Oncol.11(10),1906–1910 (1993).Crossref, Medline, CAS, Google Scholar
99 Larsen RL, Barber G, Heise CT, August CS. Exercise assessment of cardiac function in children and young adults before and after bone marrow transplantation. Pediatrics89(4 Pt 2),722–729 (1992).Medline, CAS, Google Scholar
100 Weesner KM. Exercise echocardiography in the detection of anthracycline cardiotoxicity. Cancer68(2),435–438 (1991).Crossref, Medline, CAS, Google Scholar
101 Adams MJ, Lipsitz SR, Colan SD et al. Cardiovascular status in long-term survivors of Hodgkin’s disease treated with chest radiotherapy. J. Clin. Oncol.22(15),3139–3148 (2004).▪ Identifies several, often unsuspected, cardiovascular abnormalities found in long-term survivors of Hodgkin’s disease.Crossref, Medline, Google Scholar
102 Hogenhuis J, Jaarsma T, Voors AA, Hillege HL, Lesman I, van Veldhuisen DJ. Correlates of B-type natriuretic peptide and 6-min walk in heart failure patients. Int. J. Cardiol.108(1),63–67 (2006).Crossref, Medline, Google Scholar
103 Ryberg M, Nielsen D, Skovsgaard T, Hansen J, Jensen BV, Dombernowsky P. Epirubicin cardiotoxicity: an analysis of 469 patients with metastatic breast cancer. J. Clin. Oncol.16(11),3502–3508 (1998).Crossref, Medline, CAS, Google Scholar
104 Legha SS, Benjamin RS, Mackay B et al. Adriamycin therapy by continuous intravenous infusion in patients with metastatic breast cancer. Cancer49(9),1762–1766 (1982).Crossref, Medline, CAS, Google Scholar
105 Hortobagyi GN, Frye D, Buzdar AU et al. Decreased cardiac toxicity of doxorubicin administered by continuous intravenous infusion in combination chemotherapy for metastatic breast carcinoma. Cancer63(1),37–45 (1989).Crossref, Medline, CAS, Google Scholar
106 Shapira J, Gotfried M, Lishner M, Ravid M. Reduced cardiotoxicity of doxorubicin by a 6-hour infusion regiment. A prospective evaluation. Cancer65(4),870–873 (1990).Crossref, Medline, CAS, Google Scholar
107 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.20(6),1677–1682 (2002).▪▪ Pediatric protocols have incorporated continuous infusion of anthracyclines as a means of cardioprotection based on adult findings. However, this study found that continuous doxorubicin infusion over 48 h provided no cardioprotective advantage when compared with bolus infusion. Additionally, continuous infusion can result in longer hospital stays and decreased quality of life for the patient.Crossref, Medline, CAS, Google Scholar
108 Levitt GA, Dorup I, Sorensen K, Sullivan I. Does anthracycline administration by infusion in children affect late cardiotoxicity? Br. J. Haematol.24(4),463–468 (2004).Crossref, Google Scholar
109 Singal PK, Iliskovic N. Doxorubicin-induced cardiomyopathy. N. Engl. J. Med.339(13),900–905 (1998).Crossref, Medline, CAS, Google Scholar
110 Weiss RB. The anthracyclines: will we ever find a better doxorubicin? Semin. Oncol.19(6),670–686 (1992).Medline, CAS, Google Scholar
111 Ganzina F 4´-epi-doxorubicin, a new analogue of doxorubicin: a preliminary overview of preclinical and clinical data. Cancer Treat. Rev.10(1),1–22 (1983).Crossref, Medline, CAS, Google Scholar
112 Lahtinen R, Kuikka J, Nousiainene T, Uusituoa M, Lansimies E. Cardiotoxicity of epirubicin and doxorubicin: a double-blind randomized study. Eur. J. Haematol.46(5),301–305 (1991).Crossref, Medline, CAS, Google Scholar
113 Cottin Y, Touzery C, Dalloz F et al. Comparison of epirubicin and doxorubicin cardiotoxicity induced by low doses: evolution of the diastolic and systolic parameters studies by radionuclide angiography. Clin. Cardiol.21(9),665–670 (1998).Crossref, Medline, CAS, Google Scholar
114 Dorr RT, Shipp NG, Lee KM. Comparison of cytotoxicity in heart cells and tumor cells exposed to DNA intercalating agents in vitro. Anticancer Drugs2(1),27–33 (1991).Crossref, Medline, CAS, Google Scholar
115 Alderton PM, Gross J, Green MD. Comparative study of doxorubicin, mitoxantrone, and epirubicin in combination with ICRF-187 (ADR-529) in a chronic cardiotoxicity animal model. Cancer Res.52(1),194–201 (1992).Medline, CAS, Google Scholar
116 Herman EH, Zhang J, Hasinoff BB, Clark JRJ, Ferrans VJ. Comparison of the structural changes induced by doxorubicin and mitoxantrone in the heart, kidney and intestine and characterization of the Fe(III)-mitoxantrone complex. J. Mol. Cell. Cardiol.29(9),2415–2430 (1997).Crossref, Medline, CAS, Google Scholar
117 Creutzig U, Ritter J, Zimmermann M et al. Idarubicin improves blast cell clearance during induction therapy in children with AML: results of study AML-BFM 93. AML-BFM Study Group. Leukemia15(3),348–354 (2001).Crossref, Medline, CAS, Google Scholar
118 Tardi PG, Boman NL, Cullis PR. Liposomal doxorubicin. J. Drug Target.4(3),129–140 (1996).Crossref, Medline, CAS, Google Scholar
119 Batist G, Ramakrishnan G, Rao CS et al. Reduced cardiotoxicity and preserved antitumor efficacy of liposome-encapsulated doxorubicin and cyclophosphamide compared with conventional doxorubicin and cyclophosphamide in a randomized, multicenter trial of metastatic breast cancer. J. Clin. Oncol.19(5),1444–1454 (2001).Crossref, Medline, CAS, Google Scholar
120 Harris L, Batist G, Belt R et al. Liposome-encapsulated doxorubicin compared with conventional doxorubicin in a randomized multi-center trial as first-line therapy of metastatic breast carcinoma. Cancer94(1),25–36 (2002).Crossref, Medline, CAS, Google Scholar
121 Safra T. Cardiac safety of liposomal anthracyclines. Oncologist8(2),17–24 (2003).Crossref, Medline, CAS, Google Scholar
122 Gabizon AA. Liposomal anthracyclines. Hematol. Oncol. Clin. North Am.8(2),431–450 (1994).Medline, CAS, Google Scholar
123 Money-Kyrle JF, Bates F, Ready J, Gazzard BG, Phillips RH, Boag FC. Liposomal daunorubicin in advanced Kaposi’s sarcoma: a Phase II study. Clin. Oncol. (R. Coll. Radiol.)5(6),367–371 (1993).Crossref, Medline, CAS, Google Scholar
124 Gill PS, Wernz J, Scadden DT. Randomized Phase III trial of liposomal daunorubicin versus doxorubicin, bleomycin, and vincristine in AIDS-related Kaposi’s sarcoma. J. Clin. Oncol.14(8),2353–2364 (1996).Crossref, Medline, CAS, Google Scholar
125 O’Brien ME, Wigler N, Inbar M et al. Reduced cardiotoxicity and comparable efficacy in a Phase III trial of pegylated liposomal doxorubicin HCl (CAELYX/Doxil) versus conventional doxorubicin for first-line treatment of metastatic breast cancer. Ann. Oncol.15(3),440–449 (2004).Crossref, Medline, Google Scholar
126 Sieswerda E, Kremer LC, Caron HN, van Dalen EC: The use of liposomal anthracycline analogues for childhood malignancies: a systematic review. Eur. J. Cancer47(13),2000–2008 (2011).Crossref, Medline, CAS, Google Scholar
127 Zimethbaum P, Eder H, Frishman W. Probucol: pharmacology and clinical application. J. Clin. Pharmacol.30(1),3–9 (1990).Crossref, Medline, Google Scholar
128 Carew TE, Schwenke DC, Steinberg D. Antiatherogenic effect of probucol unrelated to its hypocholesterolemic effect: evidence that antioxidants in vivo can selectively inhibit low density lipoprotein degradation in macrophage-rich fatty streaks and slow the progression of atherosclerosis in the Watanabe heritable hyperlipidemic rabbit. Proc. Natl Acad. Sci. USA84(21),7725–7729 (1987).Crossref, Medline, CAS, Google Scholar
129 Kuzuya M, Kuzuya F. Probucol as an antioxidant and antiatherogenic drug. Free Radic. Biol. Med.14(1),67–77 (1993).Crossref, Medline, CAS, Google Scholar
130 Siveski-Iliskovic N, Hill M, Chow DA, Singhal PK. Probucol protects against doxorubicin cardiomyopathy without interfering with its antitumor effect. Circulation91(1),10–15 (1995).Crossref, Medline, CAS, Google Scholar
131 Singal PK, Deally CM, Weinberg LE. Subcellular effects of doxorubicin in the heart. A concise review. J. Mol. Cell. Cardiol.19(8),817–828 (1987).Crossref, Medline, CAS, Google Scholar
132 Iliskovic N, Singal PK. Lipid lowering: an important factor in preventing doxorubicin-induced heart failure. Am. J. Pathol.150(2),727–734 (1997).Medline, CAS, Google Scholar
133 Iliskovic N, Hasinoff BB, Malisza KL, Li T, Danelisen I, Singal PK. Mechanisms of beneficial effects of probucol in doxorubicin cardiomyopathy. Mol. Cell. Biochem.196(1–2),43–49 (1999).Crossref, Medline, CAS, Google Scholar
134 Li T, Danelisen I, Bello-Klein A, Singal PK. Effects of probucol on changes of antioxidant enzymes in doxorubicin-induced cardiomyopathy in rats. Cardiovasc. Res.46(3),523–530 (2000).Crossref, Medline, CAS, Google Scholar
135 Li T, Singal PK. Adriamycin-induced early changes in myocardial antioxidant enzymes and their modulation by probucol. Circulation102(17),2105–2110 (2000).Crossref, Medline, CAS, Google Scholar
136 De Flora S, Bennicelli C, Serra D, Izzotti A, Cesarone CF. Role of glutathione and N-acetylcysteine on the mutagenicity and carcinogenesis. In: Absorption and Utilization of Amino Acids (Volume 3). Friedman M (Ed.). CRC Press, FL, USA, 19–53 (1989).Google Scholar
137 Myers CE, Bonow R, Palmeri S et al. A randomized controlled trial assessing the prevention of doxorubicin cardiomyopathy by N-acetylcysteine. Semin. Oncol.10(1),53–55 (1983).Medline, CAS, Google Scholar
138 Frishman WH. Carvedilol. Drug Therapy339(24),1759–1765 (1998).CAS, Google Scholar
139 Yue TL, Cheng HY, Lysko PG et al. Carvedilol, a new vasodilator and beta adrenoreceptor antagonist, is an antioxidant and free radical scavenger. J. Pharmacol. Exper. Therap.263(1),92–98 (1992).Medline, CAS, Google Scholar
140 Feuerstein GZ, Ruffolo RR Jr. Carvedilol, a novel multiple action antihypertensive agent with antioxidant activity and the potential for myocardial and vascular protection. Eur. Heart J.16,38–42 (1995).Crossref, Medline, CAS, Google Scholar
141 Noguchi N, Nishino K, Niki E. Antioxidant action of the antihypertensive drug, carvedilol, against lipid peroxidation. Biochem. Pharmacol.59(9),1069–1076 (2000).Crossref, Medline, CAS, Google Scholar
142 Matsui H, Morishima I, Numaguchi Y, Toki Y, Okumura K, Hayakawa T. Protective effects of carvedilol against doxorubicin-induced cardiomyopathy in rats. Life Sci.65(12),1265–1274 (1999).Crossref, Medline, CAS, Google Scholar
143 Fazio S, Palmieri EA, Ferravante B, Bone F, Biondi B, Sacca L. Doxorubicin-induced cardiomyopathy treated with carvedilol. Clin. Cardiol.21(10),777–779 (1998).Crossref, Medline, CAS, Google Scholar
144 Spallarossa P, Garibaldi S, Altieri P et al. Carvedilol prevents doxorubicin-induced free radical release and apoptosis in cardiomyocytes in vitro. J. Mol. Cell. Cardiol.37(4),837–846 (2004).Crossref, Medline, CAS, Google Scholar
145 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. Cancer104(11),2492–2498 (2005).Crossref, Medline, CAS, Google Scholar
146 Tokudome T, Mizushige K, Noma T et al. Prevention of doxorubicin (adriamycin)-induced cardiomyopathy by simultaneous administration of angiotensin-converting enzyme inhibitor assessed by acoustic densitometry. J. Cardiovasc. Pharmacol.36(3),361–368 (2000).Crossref, Medline, CAS, Google Scholar
147 Fischer PW, Salloum F, Das A, Hyder H, Kukreja RC. Phosphodiesterase-5 inhibition with Sildenafil attenuates cardiomyocyte apoptosis and left ventricular dysfunction in a chronic model of doxorubicin cardiotoxicity. Circulation111(13),1601–1610 (2005).Crossref, Medline, Google Scholar
148 Hanley PJ, Dröse S, Brandt U et al. 5-hydroxydecanoate is metabolised in mitochondria and creates a rate-limiting bottleneck for beta-oxidation of fatty acids. J. Physiol.562(2),307–318 (2005).Crossref, Medline, CAS, Google Scholar
149 Di X, Gennings C, Bear HD et al. Influence of the phosphodiesterase-5 inhibitor, Sildenafil, on sensitivity to chemotherapy in breast tumor cells. Breast Cancer Res. Treat.124(2),349–360 (2010).Crossref, Medline, CAS, Google Scholar
150 Essayan DM. Cyclic nucleotide phosphodiesterases. J. Allergy Clin. Immunol.108(5),671–680 (2001).Crossref, Medline, CAS, Google Scholar
151 Asmis R, Wang Y, Xu L, Ksgati M, Begley JG, Mieyal JJ. A novel thiol oxidation-based mechanism for adriamycin-induced cell injury in human macrophages. FASEB J.19(13),1866–1868 (2005).Crossref, Medline, CAS, Google Scholar
152 Li W, Lam MS, Birkeland A et al. Cell-based assays for profiling activity and safety properties of cancer drugs. J. Pharmacol. Toxicol. Methods.54(3),313–319 (2006).Crossref, Medline, CAS, Google Scholar
153 Raja SG, Danton MD, MacArthur, KJ, Pollock JC. Effects of escalating doses of sildenafil on hemodynamics and gas exchange in children with pulmonary hypertension and congenital cardiac defects. J. Cardiothorac. Vasc. Anesth.21(2),203–207 (2007).Crossref, Medline, CAS, Google Scholar
154 Karatza AA, Bush A, Magee AG. Safety and efficacy of sildenafil therapy in children with pulmonary hypertension. Int. J. Cardiol.100(2),267–273 (2005).Crossref, Medline, Google Scholar
155 Baquero H, Soliz A, Neira F, Venegas ME, Sola A. Oral sildenafil in infants with persistent pulmonary hypertension of the newborn: a pilot randomized blinded study. Pediatrics117(4),1077–1083 (2006).Crossref, Medline, Google Scholar
156 Juliana AE, Abbad FCB. Severe persistent pulmonary hypertension of the newborn in a setting where limited resources exclude the use of inhaled nitric oxide: successful treatment with sildenafil. Eur. J. Pediatr.164(10),626–629 (2005).Crossref, Medline, Google Scholar
157 Diez JJ, Iglesias P. The role of the novel adipocyte-derived hormone adiponectin in human disease. Eur. J. Endocrinol.148(3),293–300 (2003).Crossref, Medline, CAS, Google Scholar
158 Konishi M, Haraguchi G, Ohigashi H et al. Adiponectin protects against doxorubicin-induced cardiomyopathy by anti-apoptotic effects through AMPK upregulation. Cardiovasc. Res.89(2),309–319 (2011).Crossref, Medline, CAS, Google Scholar
159 Li L, Takemura G, Li Y et al. Preventive effect of erythropoietin on cardiac dysfunction in doxorubicin-induced cardiomyopathy. Circulation113(4),535–543 (2006).Crossref, Medline, CAS, Google Scholar
160 Hasinoff BB. The interaction of the cardioprotective agent ICRF-187 [+)-1, 2-bis(3, 5 dioxopiperazinyl-1-yL)propane); its hydrolysis product (ICRF-198); and other chelating agents with the Fe(III) and Cu(II) complexes of doxorubicin. Agents Actions26(3–4),378–385 (1989).Crossref, Medline, CAS, Google Scholar
161 Speyer JL, Green MD, Zeleniuch-Jacquotte A et al. ICRF-187 permits longer treatment with doxorubicin in women with breast cancer. J. Clin. Oncol.10(1),117–127 (1992).Crossref, Medline, CAS, Google Scholar
162 Swain SM, Whaley FS, Gerber MC, Ewer MS, Bianchine JR, Gams RA. Delayed administration of dexrazoxane provides cardioprotection for patients with advanced breast cancer treated with doxorubicin-containing therapy. J. Clin. Oncol.15(4),1333–1340 (1997).Crossref, Medline, CAS, Google Scholar
163 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.14(2),362–372 (1996).Crossref, Medline, CAS, Google Scholar
164 Swain SM, Whaley FS, Gerber MC et al. Cardioprotection with dexrazoxane for doxorubicin-containing therapy in advanced breast cancer. J. Clin. Oncol.15(4),1318–1332 (1997).Crossref, Medline, CAS, Google Scholar
165 Lopez M, Vici P, Di Lauro L et al. Randomized prospective clinical trial to evaluate cardioprotection of dexrazoxane in patients with advanced breast cancer and soft tissue sarcomas. J. Clin. Oncol.16(1),86–92 (1998).Crossref, Medline, CAS, Google Scholar
166 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.11(10),950–961 (2010).▪▪ Dexrazoxane is a clinically important cardioprotectant. This study found that dexrazoxane provides long-term cardioprotection in children with high-risk acute lymphoblastic leukemia without compromising the oncological efficacy of doxorubicin.Crossref, Medline, CAS, Google Scholar
167 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.25,493–500 (2007).Crossref, Medline, CAS, Google Scholar
168 Herman EH, Zhang J, Rifai N et al. The use of serum levels of cardiac troponin T to compare the protective activity of dexrazoxane against doxorubicin- and mitoxantrone-induced cardiotoxicity. Cancer Chemother. Pharmacol.48(4),297–304 (2001).Crossref, Medline, CAS, Google Scholar
169 Barry EV, Vrooman LM, Dahlberg SE et al. Absence of secondary malignant neoplasms in children with high-risk acute lymphoblastic leukemia treated with dexrazoxane. J. Clin. Oncol.26,1106–1111 (2008).▪▪ It has been hypothesized that dexrazoxane treatment increases risk of secondary malignant neoplasms. This study found that dexrazoxane was not associated with increased risk of secondary malignant neoplasms in children treated for high-risk acute lymphoblastic leukemia.Crossref, Medline, CAS, Google Scholar
170 Vrooman LM, Neuber DS, Stevenson KE et al. The low incidence of secondary acutemyelogenous leukaemia in children and adolescents treated with dexrazoxane for acute lymphoblastic leukaemia: a report from the Dana-Farber Cancer Institute ALL Consortium. Eur. J. Cancer47(9),1373–1379 (2011).Crossref, Medline, CAS, Google Scholar
171 Schuchter LM, Hensley ML, Meropol NJ, Winer EP. Update of recommendations for the use of chemotherapy and radiotherapy protectants: clinical practice guidelines of the American Society of Clinical Oncology. J. Clin. Oncol.20(12),2895–2903 (2002).Crossref, Medline, Google Scholar
172 Yang JL, Fernandes DJ, Speicher L, Capizzi RL. Biochemical determinants of the cytoprotective effect of amifostine. Proc. Am. Cancer Res.36,3725 (1995).Google Scholar
173 Calabro-Jones PM, Aguilera JA, Ward JF, Smoluk GD, Fahey RC. Uptake of WR-2721 derivatives by cells in cultures: identification of the transported form of the drug. Cancer Res.48(13),3634–3640 (1988).Medline, CAS, Google Scholar
174 Nazeyrollas P, Frances C, Prevost A et al. Efficiency of amifostine as a protection against doxorubicin toxicity in rats during a 12-day treatment. Anticancer Res.23(1A),405–409 (2003).Medline, CAS, Google Scholar
175 Dragojevic-Simic VM, Dobric SL, Bokonjic DR et al. Amifostine protection against doxorubicin cardiotoxicity in rats. Anticancer Drugs15(2),169–178 (2004).Crossref, Medline, CAS, Google Scholar
176 Herman EH, Ferrans VJ. Reduction of chronic doxorubicin cardiotoxicity in dogs by pretreatment with (+/-)-1, 2-bis (3, 5-dioxopipreazine-1-yl) propane (ICRF-187). Cancer Res.41(9 Pt 1),3436–3440 (1981).Medline, CAS, Google Scholar
177 The SOLVD Investigators. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N. Engl. J. Med.325(5),293–302 (1991).Crossref, Medline, Google Scholar
178 Haq MM, Legha SS, Choski J et al. Doxorubicin-induced congestive heart failure in adults. Cancer56(6),1361–1365 (1985).Crossref, Medline, CAS, Google Scholar
179 Redfield MM, Gersh BJ, Bailey KR, Rodeheffer RJ. Natural history of incidentally discovered asymptomatic idiopathic dilated cardiomyopathy. Am. J. Cardiol.74(7),737–739 (1994).Crossref, Medline, CAS, Google Scholar
180 Sieswerda E, van Dalen EC, Postma A, Cheuk DK, Caron HN, Kremer LC: Medical interventions for treating anthracycline-induced symptomatic and asymptomatic cardiotoxicity during and after treatment for childhood cancer. Cochrane Database Syst. Rev.7(9),CD008011 (2011).Google Scholar
181 Lipshultz SE, Vlach SA, Lipsitz SR et al. Cardiac changes associated with growth hormone therapy among children treated with anthracyclines. Pediatrics115,1613–1622 (2005).Crossref, Medline, Google Scholar
182 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.22(5),820–828 (2004).Crossref, Medline, CAS, Google Scholar
183 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.20,4517–4522 (2002).Medline, CAS, Google Scholar
184 Mertens AC, Sencer S, Myers CD et al. Complementary and alternative therapy use in adult survivors of childhood cancer: a report from the Childhood Cancer Survivor study. Pediatr. Blood Cancer50,90–97 (2008).Crossref, Medline, Google Scholar
185 Ibsen S, Zahavy E, Wrasdilo W, Berns M, Chan M, Esener S. A novel doxorubicin prodrug with controllable photolysis activation for cancer chemotherapy. Pharm. Res.27(9),1848–1860 (2010).Crossref, Medline, CAS, Google Scholar
186 Young K, Hare JM. Stem cells in cardiopulmonary development: Implications for novel approaches to therapy for pediatric cardiopulmonary diseases. Progr. Pediatr. Cardiol.25(3),37–49 (2008).Crossref, Google Scholar
187 Assmus B, Schachinger V, Teupe C et al. Transplantation of Progenitor Cells and Regeneration Enhancement in Acute Myocardial Infarction (TOPCARE-AMI). Circulation106(24),3009–3017 (2002).Crossref, Medline, Google Scholar
188 Schachinger V, Assmus B, Britten MB et al. Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction: final one-year results of the TOPCARE-AMI trial. J. Am. Coll. Cardiol.44(8),1690–1699 (2004).Crossref, Medline, Google Scholar
189 Wollert KC, Meyer GP, Lotz J et al. Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOST randomized controlled clinical trial. Lancet364,10–16 (2004).Crossref, Medline, Google Scholar
190 Meyer GP, Wollert KC, Lotz J et al. Intracoronary bone marrow cell transfer after myocardial infarction: eighteen months’ follow-up data from the randomized, controlled BOOST (BOnemarrOw transfer to enhance ST-elevation infarct regeneration)trial. Circulation113(10),1287–1294 (2006).Crossref, Medline, Google Scholar
191 Pillekamp F, Reppel M, Brockmeier K, Hescheler J. Stem cells and their potential relevance to paediatric cardiology. Cardiol. Young16(2),117–124 (2006).Crossref, Medline, Google Scholar
201 Childrens Oncology Group. Long-term follow-up guidelines for survivors of childhood, adolescent and young adult cancers (2008). www.survivorshipguidelines.orgGoogle Scholar

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