Seminars in Oncology
Volume 33, Issue 1 , Pages 2-14 , February 2006

Anticancer Agents and Cardiotoxicity

  • Raymond Ng

      Affiliations

    • Department of Medical Oncology, Royal Melbourne Hospital, Parkville, Victoria, Australia
    • ,
  • Nathan Better

      Affiliations

    • Department of Nuclear Medicine and Cardiology, Royal Melbourne Hospital, Parkville, Victoria, Australia
    • ,
  • Michael D. Green

      Affiliations

    • Department of Medical Oncology, Royal Melbourne Hospital, Parkville, Victoria, Australia
    • Corresponding Author InformationAddress correspondence to Associate Professor Michael Green, Department of Medical Oncology, Royal Melbourne Hospital, Grattan St, Parkville, Victoria 3050, Australia

References 

  1. Anderson R , Smith B . National Vital Statistics Reports 52 (9) . Atlanta, GA: Centers for Disease Control and Prevention/National Center for Health Statistics; 2003; November
  2. Von Hoff D , Rozencweig M , Piccart M . The cardiotoxicity of anticancer agents . Semin Oncol . 1982;9:23–33
  3. Allen A . The cardiotoxicity of chemotherapeutic drugs . Semin Oncol . 1992;19:529–542
  4. Von Hoff D , Lajard M , Basa P , et al.   Risk factors for doxorubicin-induced congestive heart failure . Ann Intern Med . 1979;91:710–717
  5. Swain S , Whaley F , Ewer M . Congestive heart failure in patients treated with doxorubicin (A retrospective analysis of three trials) . Cancer . 2003;97:2869–2879
  6. Steinherz L , Steinherz P , Tan C , et al.   Cardiac toxicity 4 to 20 years after completing anthracycline therapy . JAMA . 1991;266:1672–1677
  7. Lipshultz S , Colan S , Gelber R . Late cardiac effects of doxorubicin therapy for acute lymphoblastic leukemia in childhood . N Engl J Med . 1991;324:808–815
  8. Hequet O , Le QH , Moullet I , et al.   Subclinical late cardiomyopathy after doxorubicin therapy for lymphoma in adults . J Clin Oncol . 2004;22:1864–1871
  9. Early Breast Cancer Trialists’ Collaborative Group . Favourable and unfavourable effects on long-term survival of radiotherapy for early breast cancer (An overview of the randomised trials) . Lancet . 2000;355:1757–1770
  10. Overgaard M , Jensen M-B , Overgaard J , et al.   Postoperative radiotherapy in high-risk postmenopausal breast-cancer patients given adjuvant tamoxifen (Danish Breast Cancer Cooperative Group DBCG 82c randomised trial) . Lancet . 1999;353:1641–1648
  11. Overgaard M , Hansen P , Overgaard J , et al.   Postoperative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy . N Engl J Med . 1997;337:949–955
  12. Hitchcock-Bryan S , Gelber R , Cassady J . The impact of induction anthracycline on long-term failure-free survival in childhood acute lymphoblastic leukemia . Med Pediatr Oncol . 1986;14:211–215
  13. Smith M , Ungerleider R , Horowitz M , et al.   Influence of doxorubicin dose intensity on response and outcome for patients with osteogenic sarcoma and Ewing’s sarcoma . J Natl Cancer Inst . 1991;83:1460–1470
  14. Lipshultz S , Lipsitz S , Mone S , et al.   Female sex and drug dose as risk factors for late cardiotoxic effects of doxorubicin therapy for childhood cancer . N Engl J Med . 1995;332:1738–1743
  15. Kremer L , van der Pal H , Offringa M , et al.   Frequency and risk factors of subclinical cardiotoxicity after anthracycline therapy in children (A systematic review) . Ann Oncol . 2002;13:819–829
  16. Kremer L , van Dalen E , Offringa M , et al.   Frequency and risk factors of anthracycline-induced clinical heart failure in children (A systematic review) . Ann Oncol . 2002;13:503–512
  17. Kremer L , van Dalen E , Offringa M , et al.   Anthracycline-induced clinical heart failure in a cohort of 607 children (Long-term follow-up study) . J Clin Oncol . 2001;19:191–196
  18. Green D , Hyland A , Chung C , et al.   Cancer and cardiac mortality among 15-year survivors of cancer diagnosed during childhood or adolescence . J Clin Oncol . 1999;17:3207–3215
  19. Valdivieso M , Burgess M , Ewer M , et al.   Increased therapeutic index of weekly doxorubicin in the therapy of non-small cell lung cancer (A prospective, randomized study) . J Clin Oncol . 1984;2:207–214
  20. Torti F , Bristow M , Howes A , et al.   Reduced cardiotoxicity of doxorubicin delivered on a weekly schedule. Assessment by endomyocardial biopsy . Ann Intern Med . 1983;6:745–749
  21. Umsawasdi T , Valdivieso M , Booser D , et al.   Weekly doxorubicin versus doxorubicin every 3 weeks in cyclophosphamide, doxorubicin, and cisplatin chemotherapy for non-small cell lung cancer . Cancer . 1989;64:1995–2000
  22. Weiss A , Metter G , Fletcher W , et al.   Studies on adriamycin using a weekly regimen demonstrating its clinical effectiveness and lack of cardiac toxicity . Cancer Treat Rep . 1976;60:813–822
  23. Legha S , Benjamin R , Mackay B , et al.   Reduction of doxorubicin cardiotoxicity by prolonged continuous intravenous infusion . Ann Intern Med . 1982;96:133–139
  24. Hortobagyi G , Frye D , Buzdar A , et al.   Decreased cardiac toxicity of doxorubicin administered by continuous intravenous infusion in combination chemotherapy for metastatic breast carcinoma . Cancer . 1989;63:37–45
  25. Shapira J , Gotfried M , Lishner M , et al.   Reduced cardiotoxicity of doxorubicin by a 6-hour infusion regimen. A prospective randomized evaluation . Cancer . 1990;65:870–873
  26. Speyer J , Green M , Dubin N , et al.   Prospective evaluation of cardiotoxicity during a six-hour doxorubicin infusion regimen in women with adenocarcinoma of the breast . Am J Med . 1985;78:555–563
  27. Lipshultz S , Giantris A , Lipsitz S , et al.   Doxorubicin administration by continuous infusion is not cardioprotective (The Dana-Farber 91-01 Acute Lymphoblastic Leukemia protocol) . J Clin Oncol . 2002;20:1677–1682
  28. Jain K , Casper E , Geller N , et al.   A prospective randomized comparison of epirubicin and doxorubicin in patients with advanced breast cancer . J Clin Oncol . 1985;3:818–826
  29. Jensen B , Skovsgaard T , Nielsen S , et al.   Functional monitoring of anthracycline cardiotoxicity (A prospective, blinded, long-term observational study of outcome in 120 patients) . Ann Oncol . 2002;13:699–709
  30. Ryberg M , Nielsen D , Skovsgaard T , et al.   Epirubicin cardiotoxicity (An analysis of 469 patients with metastatic breast cancer) . J Clin Oncol . 1998;16:3502–3508
  31. The Italian Multicentre Breast Study With Epirubicin . Phase III randomized study of fluorouracil, epirubicin, and cyclophosphamide v fluorouracil, doxorubicin, and cyclophosphamide in advanced breast cancer (An Italian multicentre trial) . J Clin Oncol . 1988;6:976–982
  32. The French Epirubicin Study Group . A prospective randomized phase III trial comparing combination chemotherapy with cyclophosphamide, fluorouracil, and either doxorubicin or epirubicin . J Clin Oncol . 1988;6:679–688
  33. The French Adjuvant Study Group . Benefit of a high-dose epirubicin regimen in adjuvant chemotherapy for node-positive breast cancer patients with poor prognosis factors (5-year follow-up results of French Adjuvant Study Group 05 randomized trial) . J Clin Oncol . 2001;19:602–611
  34. Fumoleau P , Kerbrat P , Romestaing P , et al.   Randomized trial comparing six versus three cycles of epirubicin-based adjuvant chemotherapy in premenopausal, node-positive breast cancerpatients (10-year follow-up results of the French Adjuvant Study Group 01 trial) . J Clin Oncol . 2003;l21:298–305
  35. Myers C , Gianni L , Zweier J , et al.   Role of iron in Adriamycin biochemistry . Fed Proc . 1986;45:2792–2797
  36. Creighton A , Hellmann K , Whitecross S . Antitumour activity in a series of bisdiketopiperazines . Nature . 1969;222:384–385
  37. Von Hoff D , Howser D , Lewis B . Phase I study of ICRF-187 using a daily for 3 days schedule . Cancer Treat Rep . 1981;65:249–252
  38. Wexler L , Andrich M , Venzon D , et al.   Randomized trial of the cardioprotective agent ICRF-187 in pediatric sarcoma patients treated with doxorubicin . J Clin Oncol . 1996;14:362–372
  39. Venturini M , Michelotti A , Del Mastro L , et al.   Multicenter randomized controlled clinical trial to evaluate cardioprotection of dexrazoxane versus no cardioprotection in women receiving epirubicin chemotherapy for advanced breast cancer . J Clin Oncol . 1996;14:3112–3120
  40. Lopez M , Vici P , Di Lauro K , et al.   Randomized prospective clinical trial of high-dose epirubicin and dexrazoxane in patients with advanced breast cancer and soft tissue sarcomas . J Clin Oncol . 1998;16:86–92
  41. Feldmann J , Jones S , Weisberg S , et al.   Advanced small cell lung cancer treated with CAV (cyclophosphamide, Adriamycin + vincristine) chemotherapy and the cardioprotective agent dexrazoxane (ADR529, ICRF-187. Zinecard) . Proc Am Soc Clin Oncol . 1992;11:296; (abstr 993)
  42. Speyer J , Green M , Zeleniuch-Jacquotte A , et al.   ICRF-187 permits longer treatment with doxorubicin in women with breast cancer . J Clin Oncol . 1992;10:117–127
  43. Seymour L , Bramwell V , Moran L  The Provincial Systemic Treatment Disease Site Group . Use of dexrazoxane as a cardioprotectant in patients receiving doxorubicin or epirubicin chemotherapy for the treatment of cancer . Cancer Prev Control . 1999;3:145–149
  44. Swain S , Whaley F , Gerber M , et al.   Cardioprotection with dexrazoxane for doxorubicin-containing therapy in advanced breast cancer . J Clin Oncol . 1997;15:1318–1332
  45. Swain S , Whaley F , Gerber M , et al.   Delayed administration of dexrazoxane provides cardioprotection for patients with advanced breast cancer treated with doxorubicin-containing therapy . J Clin Oncol . 1997;15:1333–1340
  46. Schuchter L , Hensley M , Neal J , et al.   2002 update of recommendations for the use of chemotherapy and radiotherapy protectants (Clinical practice guidelines of the American Society of Clinical Oncology) . J Clin Oncol . 2002;20:2895–2903
  47. Batist G , Ramakrishnan G , Rao C , et al.   Reduced cardiotoxicity and preserved antitumour 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 . 2001;19:1444–1454
  48. Swenson C , Bolcsak L , Batist G , et al.   Pharmacokinetics of doxorubicin administered i.v. as Myocet (TLC D-99; liposome-encapsulated doxorubicin citrate) compared with conventional doxorubicin when given in combination with cyclophosphamide in patients with metastatic breast cancer . Anticancer Drugs . 2003;14:239–246
  49. Chan S , Davidson N , Juozaityte E , et al.   Phase III study of liposome-encapsulated doxorubicin (TLC D-99) and cyclophosphamide (CPA) vs. epirubicin (EPI) and CPA in first-line treatment of metastatic breast cancer (MBC). Abstracts and Proceedings from ECCO 1999 . (Abstract: 1263) Eur J Cancer . 1999;35:315
  50. Harris L , Batist G , Belt R , et al.   Liposome-encapsulated doxorubicin compared with conventional doxorubicin in a randomized multicenter trial as first-line therapy of metastatic breast carcinoma . Cancer . 2002;94:25–36
  51. Williams G , Cortazar P , Pazdur R . Developing drugs to decrease the toxicity of chemotherapy . J Clin Oncol . 2001;19:3439–3441
  52. Storm G , Kate M , Working P , et al.   Doxorubicin entrapped in sterically stabilized liposomes (Effects on bacterial blood clearance capacity of the mononuclear phagocyte system) . Clin Cancer Res . 1998;4:111–115
  53. Symon Z , Peyser A , Tzemach D , et al.   Selective delivery of doxorubicin to patients with breast carcinoma metastases by stealth liposomes . Cancer . 1999;86:72–78
  54. O’Brien M , Wigler  , Inbar N , 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 . 2004;15:440–449
  55. Theodoulou M , Campos S , Batist G , et al.   TLC D99 (D, Myocet) and Herceptin (H) is safe in advanced breast cancer (ABC) (Final cardiac safety and efficacy analysis) . Proc Am Soc Clin Oncol . 2002;21:55a; (abstr 216)
  56. Jones V , Finucane D , Rodriguez R , et al.   Phase II study of weekly paclitaxel (Taxol) and liposomal doxorubicin (Doxil) in patients with locally advanced and metastatic breast cancer . Proc Am Soc Clin Oncol . 2000;19:116a; (abstr 451)
  57. Gogas H , Papadimitriou C , Kalofonos H , et al.   Neoadjuvant chemotherapy with a combination of pegylated liposomal doxorubicin (Caelyx) and paclitaxel in locally advanced breast cancer (A phase II study by the Hellenic Cooperative Oncology Group) . Ann Oncol . 2002;13:1737–1742
  58. Slamon D , Leyland-Jones B , Shak S , et al.   Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2 . N Engl J Med . 2001;344:783–792
  59. Billingham M , Bristow M . Evaluation of endomyocardial cardiotoxicity (predictive ability and functional correlation of endomyocardial biopsy) . Cancer Treat Symp . 1984;3:71–76
  60. Bristow M , Mason J , Billingham M , et al.   Doxorubicin cardiomyopathy (Evaluation by phonocardiography, endomyocardial biopsy, and cardiac catheterization) . Ann Intern Med . 1978;88:168–175
  61. Friedman M , Bozdech M , Billingham M , et al.   Doxorubicin cardiotoxicity. Serial endomyocardial biopsies and systolic time intervals . JAMA . 1978;240:1603–1606
  62. Ewer M , Ali M , Mackay B . A comparison of cardiac biopsy grades and ejection fraction estimation in patients receiving adriamycin . J Clin Oncol . 1984;2:112–117
  63. Isner J , Ferrans V , Cohen S , et al.   Clinical and morphologic cardiac findings after anthracycline chemotherapy. Analysis of 64 patients studied at necropsy . Am J Cardiol . 1983;51:1167–1174
  64. Schwartz R , McKenzie W , Alexander J , et al.   Congestive heart failure and left ventricular dysfunction complicating doxorubicin therapy. Seven-year experience using serial radionuclide angiocardiography . Am J Med . 1987;82:1109–1118
  65. Mitani I , Jain D , Joska T , et al.   Doxorubicin cardiotoxicity (Prevention of congestive heart failure with serial cardiac function monitoring with equilibrium radionuclide angiocardiography in the current era) . J Nucl Cardiol . 2003;10:132–139
  66. Ganz W , Sridhar K , Forness T . Detection of early anthracycline cardiotoxicity by monitoring the peak filling rate . Am J Clin Oncol . 1993;16:109–112
  67. Stoddard M , Seeger J , Liddell N , et al.   Prolongation of isovolumetric relaxation time as assessed by Doppler echocardiography predicts doxorubicin-induced systolic dysfunction in humans . J Am Coll Cardiol . 1992;20:62–69
  68. Hiroe M , Ohta Y , Fujita N , et al.   Myocardial uptake of 111In monoclonal antimyosin Fab in detecting doxorubicin cardiotoxicity in rats. Morphological and hemodynamic findings . Circulation . 1992;86:1965–1972
  69. Valdes Olmos R , Carrio I , Hoefnagel C , et al.   High sensitivity of radiolabelled antimyosin scintigraphy in assessing anthracycline related early myocyte damage preceding cardiac dysfunction . Nucl Med Commun . 2002;23:871–877
  70. Carrio I , Lopez-Pousa A , Estorch M , et al.   Detection of doxorubicin cardiotoxicity in patients with sarcomas by indium-111-antimyosin monoclonal antibody studies . J Nucl Med . 1993;34:1503–1507
  71. Ohman E , Armstrong P , Christenson R , et al.   Cardiac troponin T levels for risk stratification in acute myocardial ischemia . N Engl J Med . 1996;335:1333–1341
  72. Antman E , Tanasijevic M , Thompson B , et al.   Cardiac-specific troponin I levels to predict the risk of mortality in patients with acute coronary syndromes . N Engl J Med . 1996;335:1342–1349
  73. Lindahl B , Venge P , Wallentin L . Relation between troponin T and the risk of subsequent cardiac events in unstable coronary artery disease . Circulation . 1996;93:1651–1657
  74. Herman E , Zhang J , Lipshultz S , et al.   Correlation between serum levels of cardiac troponin-T and the severity of the chronic cardiomyopathy induced by doxorubicin . J Clin Oncol . 1999;17:2237–2243
  75. Herman E , 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 . 2001;48:297–304
  76. Missov E , Calzolari C , Davy J , et al.   Cardiac troponin I in patients with hematologic malignancies . Coron Artery Dis . 1997;8:537–541
  77. Raderer M , Gabriela K , Weinlander G , et al.   Serum troponin levels in adults undergoing anthracycline therapy . J Natl Cancer Inst . 1997;89:171; (letter)
  78. Lipshultz S , Rifai N , Sallan S , et al.   Predictive value of cardiac troponin T in pediatric patients at risk for myocardial injury . Circulation . 1997;96:2641–2648
  79. Kismet E , Varan A , Ayabakan C , et al.   Serum troponin T levels and echocardiographic evaluation in children treated with doxorubicin . Pediatr Blood Cancer . 2004;42:220–224
  80. Kremer L , Bastiaansen B , Offringa M , et al.   Troponin T in the first 24 hours after the administration of chemotherapy and the detection of myocardial damage in children . Eur J Cancer . 2002;38:686–689
  81. Cardinale D , Sandri MT , Martinoni A , et al.   Left ventricular dysfunction predicted by early troponin I release after high-dose chemotherapy . J Am Coll Cardiol . 2000;36:517–522
  82. Newby L , Goldmann B , Ohman E . Troponin (an important prognostic marker and risk-stratification tool in non-ST-segment elevation acute coronary syndromes) . J Am Coll Cardiol . 2003;41(suppl S):31S–36S
  83. Yalamanchili K , Sukhija R , Aronow W , et al.   Prevalence of increased cardiac troponin I levels in patients with and without acute pulmonary embolism and relation of increased cardiac troponin I levels with in-hospital mortality in patients with acute pulmonary embolism . Am J Cardiol . 2004;93:263–264
  84. Ammann P , Maggiorini M , Bertel O , et al.   Troponin as a risk factor for mortality in critically ill patients without acute coronary syndromes . J Am Coll Cardiol . 2003;4:2004–2009
  85. Chan S , Friedrichs K , Noel D , et al.   Prospective randomized trial of docetaxel versus doxorubicin in patients with metastatic breast cancer . J Clin Oncol . 1999;17:2341–2354
  86. Sledge G , Neuberg D , Bernardo P , et al.   Phase III trial of doxorubicin, paclitaxel, and the combination of doxorubicin and paclitaxel as front-line chemotherapy for metastatic breast cancer (An Intergroup trial (E1193)) . J Clin Oncol . 2003;21:588–592
  87. Gianni L , Munzone E , Capri G , et al.   Paclitaxel by 3-hour infusion in combination with bolus doxorubicin in women with untreated metastatic breast cancer (High antitumor efficacy and cardiac effects in a dose-finding and sequence-finding study) . J Clin Oncol . 1995;13:2688–2699
  88. Gehl J , Boesgaard M , Paaske T , et al.   Combined doxorubicin and paclitaxel in advanced breast cancer (Effective and cardiotoxic) . Ann Oncol . 1996;7:687–693
  89. Gianni L , Vigano L , Locatelli A , et al.   Human pharmacokinetic characterization and in vitro study of the interaction between doxorubicin and paclitaxel in patients with breast cancer . J Clin Oncol . 1997;15:1906–1915
  90. Holmes F , Madden T , Newman R , et al.   Sequence-dependent alteration of doxorubicin pharmacokinetics by paclitaxel in a phase I study of paclitaxel and doxorubicin in patients with metastatic breast cancer . J Clin Oncol . 1996;14:2713–2721
  91. Gianni L , Capri G . Experience at the Instituto Nazionale Tumori with paclitaxel in combination with doxorubicin in women with untreated breast cancer . Semin Oncol . 1997;24:S3-1–S3-3
  92. Biganzoli L , Cufer T , Bruning P , et al.   Doxorubicin-paclitaxel. A safe regimen in terms of cardiac toxicity in metastatic breast carcinoma patients. Results from a European Organization for Research and Treatment of Cancer multicenter trial . Cancer . 2003;97:40–45
  93. Jassem J , Pienkowski T , Pluzanska A , et al.   Doxorubicin and paclitaxel versus fluorouracil, doxorubicin, and cyclophosphamide as first-line therapy for women with metastatic breast cancer (Final results of a randomized phase III multicenter trial) . J Clin Oncol . 2001;19:1707–1715
  94. Bellot R , Robert J , Dieras V , et al.   Taxotere does not change the pharmacokinetic profile of doxorubicin and doxorubincinol . Proc Am Soc Clin Oncol . 1998;12:221a; (abstr 853)
  95. Schuller J , Czejka M , Kletzl H , et al.   Doxorubicin and Taxotere (A pharmacokinetic study of the combination in advanced breast cancer) . Proc Am Soc Clin Oncol . 1998;17:205a; (abstr 790)
  96. Nabholtz J-M , Falkson C , Campos D , et al.   Docetaxel and doxorubicin compared with doxorubicin and cyclophosphamide as first-line chemotherapy for metastatic breast cancer (Results of a randomized, multicenter, phase III trial) . J Clin Oncol . 2003;21:968–975
  97. Mackey J , Paterson A , Dirix L , et al.   Final results of the phase III randomized trial comparing docetaxel (T), doxorubicin (A) and cyclophosphamide (C) to FAC as first-line chemotherapy (CT) for patients (pts) with metastatic breast cancer (MBC) . Proc Am Soc Clin Oncol . 2002;21:137; (abstr 137)
  98. Martin M , Pienkowski T , Mackey J , et al.   Adjuvant docetaxel for node-positive breast cancer . N Engl J Med . 2005;352:2302–2313
  99. Luck H , Thomssen C , Untch M , et al.   Multicentric phase III study in first line treatment of advanced metastatic breast cancer (ABC) (epirubicin/paclitaxel (ET) vs epirubicin/cyclophosphamide (EC). A study of the AGO Breast Cancer Group) . Proc Am Soc Clin Oncol . 2000;19:73; (abstr 280)
  100. Sessa C , Pagani O . Docetaxel and epirubicin in advanced breast cancer . Oncologist . 2001;6:13–16
  101. Slamon D , Clark G , Wong S , et al.   Human breast cancer (Correlation of relapse and survival with amplification of the HER-2/neu oncogene) . Science . 1987;235:177–182
  102. Cobleigh M , Vogel C , Tripathy D , et al.   Multinational study of the efficacy and safety of humanized anti-HER2 monoclonal antibody in women who have HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease . J Clin Oncol . 1999;17:2639–2648
  103. Vogel C , Cobleigh M , Tripathy D , et al.   Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer . J Clin Oncol . 2002;20:719–726
  104. Baselga J , Tripathy D , Mendelsohn J , et al.   Phase II study of weekly intravenous recombinant humanized anti-p185HER2 monoclonal antibody in patients with HER2/neu-overexpressing metastatic breast cancer . J Clin Oncol . 1996;14:737–744
  105. Seidman A , Hudis C , Pierri MK , et al.   Cardiac dysfunction in the trastuzumab clinical trials experience . J Clin Oncol . 2002;20:1215–1221
  106. Tripathy D , Slamon D , Cobleigh M , et al.   Safety of treatment of metastatic breast cancer with trastuzumab beyond disease progression . J Clin Oncol . 2004;22:1063–1070
  107. Schneider JW , Chang AY , Garratt A . Trastuzumab cardiotoxicity (Speculations regarding pathophysiology and targets for further study) . Semin Oncol . 2002;3(suppl 11):22–28
  108. Crone SA , Zhao YY , Fan L , et al.   ErbB2 is essential in the prevention of dilated cardiomyopathy . Nat Med . 2002;8:459–465
  109. Behr T , Behe M , Wormann B , et al.   Trastuzumab and breast cancer . N Engl J Med . 2001;345:995–998
  110. Burstein H , Harris L , Marcom P , et al.   Trastuzumab and vinorelbine as first-line therapy for HER2-overexpressing metastatic breast cancer (Multicenter phase II trial with clinical outcomes, analysis of serum tumor markers as predictive factors, and cardiac surveillance algorithm) . J Clin Oncol . 2003;21:2889–2895
  111. Pegram M , Pienkowski T , Northfelt D , et al.   Results of two open-label, multicenter phase II studies of docetaxel, platinum salts, and trastuzumab in HER2-positive advanced breast cancer . J Natl Cancer Inst . 2004;96:759–769
  112. Montemurro F , Choa G , Faggiuolo R , et al.   A phase II study of three-weekly docetaxel and weekly trastuzumab in HER2-overexpressing advanced breast cancer . Oncology . 2004;66:38–45
  113. Esteva F , Valero V , Booser D , et al.   Phase II study of weekly docetaxel and trastuzumab for patients with HER-2-overexpressing metastatic breast cancer . J Clin Oncol . 2002;20:1800–1808
  114. Tedesco K , Thor A , Johnson D , et al.   Docetaxel combined with trastuzumab is an active regimen in HER-2 3+ overexpressing and fluorescent in situ hybridization-positive metastatic breast cancer (A multi-institutional phase II trial) . J Clin Oncol . 2004;22:1071–1077
  115. Piccart-Gebhart M , Procter M , Leyland-Jones B , et al.   Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer . N Engl J Med . 2005;353:1659–1672
  116. Romond E , Perez E , Bryant J , et al.   Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer . N Engl J Med . 2005;353:1673–1684
  117. Perez E , Suman V , Davidson N , et al.   Interim cardiac safety analysis of NCCTG N9831 Intergroup adjuvant trastuzumab trial . Proc Am Soc Clin Oncol . 2005;23:16S; (abstr 556)
  118. Tan-Chiu E , Yothers G , Romond E , et al.   Assessment of cardiac dysfunction in a randomized trial comparing doxorubicin and cyclophosphamide followed by paclitaxel, with or without trastuzumab as adjuvant therapy in node-positive, human epidermal growth factor receptor 2-overexpressing breast cancer (NSABP B-31) . J Clin Oncol . 2005;23:7811–7819
  119. Ewer M , Vooletich M , Durand J , et al.   Reversibility of trastuzumab-related cardiotoxicity (New insights based on clinical course and response to medical treatment) . J Clin Oncol . 2005;23:7820–7826
  120. Jensen BV , Skovsgaard T , Nielsen SL . Functional monitoring of anthracycline cardiotoxicity (A prospective, blinded, long-term observational study of outcome in 120 patients) . Ann Oncol . 2002;13:699–709
  121. The SOLVD Investigators . Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions . N Engl J Med . 1992;327:685–689
  122. Yusuf S , Sleight P , Pogue J , et al.  The Heart Outcomes Prevention Evaluation Study Investigators   Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients . N Engl J Med . 2000;342:145–153
  123. Hjalmarson A , Goldstein S , Fagerberg B , et al.  MERIT-HF Study Group   Effects of controlled-release metoprolol on total mortality, hospitalizations, and well-being in patients with heart failure (The Metoprolol CR/XL Randomized Intervention Trial in congestive heart failure (MERIT-HF)) . JAMA . 2000;283:1295–1302
  124. Packer M , Fowler M , Roecker E , et al.   Effect of carvedilol on the morbidity of patients with severe chronic heart failure (Results of the Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) study) . Circulation . 2002;106:2194–2199
  125. CIBIS-II Investigators and Committees . The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II) (A randomised trial) . Lancet . 1999;353:9–13
  126. Remme W , Riegger G , Hildebrandt P , et al.   The benefits of early combination treatment of carvedilol and an ACE-inhibitor in mild heart failure and left ventricular systolic dysfunction. The Carvedilol and ACE-Inhibitor Remodelling Mild Heart Failure Evaluation Trial (CARMEN) . Cardiovasc Drugs Ther . 2004;18:57–66
  127. Pitt B , Zannad F , Remme W , et al.   The effect of spironolactone on morbidity and mortality in patients with sever heart failure (Randomized Aldactone Evaluation Study Investigators) . N Engl J Med . 1999;341:709–717
  128. Lipshultz S , Lipsitz S , Sallan S , et al.   Long-term enalapril therapy for left ventricular dysfunction in doxorubicin-treated survivors of childhood cancer . J Clin Oncol . 2002;20:4517–4522
  129. Silber J , Cnaan A , Clark B , et al.   Enalapril to prevent cardiac function decline in long-term survivors of pediatric cancer exposed to anthracyclines . J Clin Oncol . 2004;22:820–828

PII: S0093-7754(05)00430-6

doi: 10.1053/j.seminoncol.2005.11.001

Seminars in Oncology
Volume 33, Issue 1 , Pages 2-14 , February 2006

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