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. 1983 Sep;139(3):332–341.

Doxorubicin (Adriamycin) Cardiomyopathy—A Critical Review

Emmanuel Saltiel, William McGuire
PMCID: PMC1021516  PMID: 6356608

Abstract

Despite its vast utility in clinical oncology, the use of doxorubicin hydrochloride (Adriamycin) is limited by a potentially fatal cardiomyopathy. The following critical review, which examines the natural course, histopathologic effects, risk factors and monitoring indicators of this toxicity, also analyzes recent research of proposed mechanisms, including free radical formation with depletion of detoxifying enzymes, inhibition of vital enzyme systems and alterations in relative calcium concentrations. Prevention of the adverse reaction has been attempted by using such agents as α-tocopherol, selenium sulfide, coenzyme Q10, sulfhydryl donors, nucleosides and razoxane, and via liposomal carriage and alternative methods of administration.

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Selected References

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  1. Al-Ismail S., Whittaker J. A. Systolic time interval as index of schedule--dependent doxorubicin cardiotoxicity in patients with acute myelogenous leukaemia. Br Med J. 1979 May 26;1(6175):1392–1395. doi: 10.1136/bmj.1.6175.1392. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Alexander J., Dainiak N., Berger H. J., Goldman L., Johnstone D., Reduto L., Duffy T., Schwartz P., Gottschalk A., Zaret B. L. Serial assessment of doxorubicin cardiotoxicity with quantitative radionuclide angiocardiography. N Engl J Med. 1979 Feb 8;300(6):278–283. doi: 10.1056/NEJM197902083000603. [DOI] [PubMed] [Google Scholar]
  3. Ali M. K., Soto A., Maroongroge D., Bekheit-Saad S., Buzdar A. U., Blumenschein G. R., Hortobagyi G. N., Tashima C. K., Wiseman C. L., Shullenberger C. C. Electrocardiographic changes after adriamycin chemotherapy. Cancer. 1979 Feb;43(2):465–471. doi: 10.1002/1097-0142(197902)43:2<465::aid-cncr2820430210>3.0.co;2-r. [DOI] [PubMed] [Google Scholar]
  4. Bachur N. R., Gordon S. L., Gee M. V., Kon H. NADPH cytochrome P-450 reductase activation of quinone anticancer agents to free radicals. Proc Natl Acad Sci U S A. 1979 Feb;76(2):954–957. doi: 10.1073/pnas.76.2.954. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Benjamin R. S., Mason J. W., Billingham M. E. Cardiac toxicity of adriamycin-DNA complex and rubidazone: evaluation by electrocardiogram and endomyocardial biopsy. Cancer Treat Rep. 1978 Jun;62(6):935–939. [PubMed] [Google Scholar]
  6. Beretta G., Villani F. Cardiomyopathy in adults after combination adriamycin and DTIC. Cancer Treat Rep. 1980 Feb-Mar;64(2-3):353–353. [PubMed] [Google Scholar]
  7. Berlin V., Haseltine W. A. Reduction of adriamycin to a semiquinone-free radical by NADPH cytochrome P-450 reductase produces DNA cleavage in a reaction mediated by molecular oxygen. J Biol Chem. 1981 May 25;256(10):4747–4756. [PubMed] [Google Scholar]
  8. Bhanot P., Cushing B., Philippart A., Das L., Farooki Z. Hepatic irradiation and adriamycin cardiotoxicity. J Pediatr. 1979 Oct;95(4):561–563. doi: 10.1016/s0022-3476(79)80767-2. [DOI] [PubMed] [Google Scholar]
  9. Biancaniello T., Meyer R. A., Wong K. Y., Sager C., Kaplan S. Doxorubicin cardiotoxicity in children. J Pediatr. 1980 Jul;97(1):45–50. doi: 10.1016/s0022-3476(80)80128-4. [DOI] [PubMed] [Google Scholar]
  10. Billingham M. E., Mason J. W., Bristow M. R., Daniels J. R. Anthracycline cardiomyopathy monitored by morphologic changes. Cancer Treat Rep. 1978 Jun;62(6):865–872. [PubMed] [Google Scholar]
  11. Breed J. G., Zimmerman A. N., Dormans J. A., Pinedo H. M. Failure of the antioxidant vitamin E to protect against adriamycin-induced cardiotoxicity in the rabbit. Cancer Res. 1980 Jun;40(6):2033–2038. [PubMed] [Google Scholar]
  12. Bristow M. R., Billingham M. E., Mason J. W., Daniels J. R. Clinical spectrum of anthracycline antibiotic cardiotoxicity. Cancer Treat Rep. 1978 Jun;62(6):873–879. [PubMed] [Google Scholar]
  13. Bristow M. R., Mason J. W., Billingham M. E., Daniels J. R. Dose-effect and structure-function relationships in doxorubicin cardiomyopathy. Am Heart J. 1981 Oct;102(4):709–718. doi: 10.1016/0002-8703(81)90096-x. [DOI] [PubMed] [Google Scholar]
  14. Bristow M. R., Mason J. W., Billingham M. E., Daniels J. R. Doxorubicin cardiomyopathy: evaluation by phonocardiography, endomyocardial biopsy, and cardiac catheterization. Ann Intern Med. 1978 Feb;88(2):168–175. doi: 10.7326/0003-4819-88-2-168. [DOI] [PubMed] [Google Scholar]
  15. Buzdar A. U., Legha S. S., Tashima C. K., Hortobagyi G. N., Yap H. Y., Krutchik A. N., Luna M. A., Blumenschein G. R. Adriamycin and mitomycin C: possible synergistic cardiotoxicity. Cancer Treat Rep. 1978 Jul;62(7):1005–1008. [PubMed] [Google Scholar]
  16. Chlebowski R. T. Adriamycin (doxorubicin) cardiotoxicity: a review. West J Med. 1979 Nov;131(5):364–368. [PMC free article] [PubMed] [Google Scholar]
  17. Chlebowski R. T., Paroly W. S., Pugh R. P., Hueser J., Jacobs E. M., Pajak T. F., Bateman J. R. Adriamycin given as a weekly schedule without a loading course: clinically effective with reduced incidence of cardiotoxicity. Cancer Treat Rep. 1980 Jan;64(1):47–51. [PubMed] [Google Scholar]
  18. Choe J. Y., Combs A. B., Saji S., Folkers K. Study of the combined and separate administration of doxorubicin and coenzyme Q10 on mouse cardiac enzymes. Res Commun Chem Pathol Pharmacol. 1979 Jun;24(3):595–598. [PubMed] [Google Scholar]
  19. Chow C. K., Tappel A. L. Response of glutathione peroxidase to dietary selenium in rats. J Nutr. 1974 Apr;104(4):444–451. doi: 10.1093/jn/104.4.444. [DOI] [PubMed] [Google Scholar]
  20. Copeland J. G., Salomon N. W. Endomyocardial biopsy. Ariz Med. 1980 May;37(5):327–328. [PubMed] [Google Scholar]
  21. Cortes E. P., Gupta M., Chou C., Amin V. C., Folkers K. Adriamycin cardiotoxicity: early detection by systolic time interval and possible prevention by coenzyme Q10. Cancer Treat Rep. 1978 Jun;62(6):887–891. [PubMed] [Google Scholar]
  22. Domae N., Sawada H., Matsuyama E., Konishi T., Uchino H. Cardiomyopathy and other chronic toxic effects induced in rabbits by doxorubicin and possible prevention by coenzyme Q10. Cancer Treat Rep. 1981 Jan-Feb;65(1-2):79–91. [PubMed] [Google Scholar]
  23. Doroshow J. H., Locker G. Y., Myers C. E. Enzymatic defenses of the mouse heart against reactive oxygen metabolites: alterations produced by doxorubicin. J Clin Invest. 1980 Jan;65(1):128–135. doi: 10.1172/JCI109642. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Doroshow J. H., Locker G. Y., Myers C. E. Experimental animal models of adriamycin cardiotoxicity. Cancer Treat Rep. 1979 May;63(5):855–860. [PubMed] [Google Scholar]
  25. Ferrans V. J. Overview of cardiac pathology in relation to anthracycline cardiotoxicity. Cancer Treat Rep. 1978 Jun;62(6):955–961. [PubMed] [Google Scholar]
  26. Flohé L., Zimmermann R. The role of GSH peroxidase in protecting the membrane of rat liver mitochondria. Biochim Biophys Acta. 1970 Nov 3;223(1):210–213. doi: 10.1016/0005-2728(70)90149-0. [DOI] [PubMed] [Google Scholar]
  27. Formelli F., Zedeck M. S., Sternberg S. S., Philips F. S. Effects of adriamycin on DNA synthesis in mouse and rat heart. Cancer Res. 1978 Oct;38(10):3286–3292. [PubMed] [Google Scholar]
  28. Friedman M. A., Bozdech M. J., Billingham M. E., Rider A. K. Doxorubicin cardiotoxicity. Serial endomyocardial biopsies and systolic time intervals. JAMA. 1978 Oct 6;240(15):1603–1606. doi: 10.1001/jama.240.15.1603. [DOI] [PubMed] [Google Scholar]
  29. Friedman M. J., Ewy G. A., Jones S. E., Cruze D., Moon T. E. 1-year followup of cardiac status after adriamycin therapy. Cancer Treat Rep. 1979 Nov-Dec;63(11-12):1809–1816. [PubMed] [Google Scholar]
  30. Fulkerson P. K., Talley R., Kleinman D., Weaver S. K., Leier C. V., Balcerzak S. P., Lewis R. P. Noninvasive profile in the prospective monitoring of adriamycin cardiomyopathy. Cancer Treat Rep. 1978 Jun;62(6):881–886. [PubMed] [Google Scholar]
  31. Giuliani F., Casazza A. M., Di Marco A., Savi G. Studies in mice treated with ICRF-159 combined with daunorubicin or doxorubicin. Cancer Treat Rep. 1981 Mar-Apr;65(3-4):267–276. [PubMed] [Google Scholar]
  32. Goldsmith M. A., Suzuki Y., Ohnuma T., Holland J. F. Failure of carnitine to prevent adriamycin cardiomyopathy. Cancer Treat Rep. 1979 Apr;63(4):558–560. [PubMed] [Google Scholar]
  33. Goorin A. M., Borow K. M., Goldman A., Williams R. G., Henderson I. C., Sallan S. E., Cohen H., Jaffe N. Congestive heart failure due to adriamycin cardiotoxicity: its natural history in children. Cancer. 1981 Jun 15;47(12):2810–2816. doi: 10.1002/1097-0142(19810615)47:12<2810::aid-cncr2820471210>3.0.co;2-4. [DOI] [PubMed] [Google Scholar]
  34. Gottdiener J. S., Appelbaum F. R., Ferrans V. J., Deisseroth A., Ziegler J. Cardiotoxicity associated with high-dose cyclophosphamide therapy. Arch Intern Med. 1981 May;141(6):758–763. [PubMed] [Google Scholar]
  35. Gottdiener J. S., Mathisen D. J., Borer J. S., Bonow R. O., Myers C. E., Barr L. H., Schwartz D. E., Bacharach S. L., Green M. V., Rosenberg S. A. Doxorubicin cardiotoxicity: assessment of late left ventricular dysfunction by radionuclide cineangiography. Ann Intern Med. 1981 Apr;94(4 Pt 1):430–435. doi: 10.7326/0003-4819-94-4-430. [DOI] [PubMed] [Google Scholar]
  36. Gottlieb S. L., Edmiston W. A., Jr, Haywood L. J. Late, late doxorubicin cardiotoxicity. Chest. 1980 Dec;78(6):880–882. doi: 10.1378/chest.78.6.880. [DOI] [PubMed] [Google Scholar]
  37. Gralla E. J., Fleischman R. W., Luthra Y. K., Stadnicki S. W. The dosing schedule dependent toxicities of adriamycin in beagle dogs and rhesus monkeys. Toxicology. 1979 Aug;13(3):263–273. [PubMed] [Google Scholar]
  38. Guthrie D., Gibson A. L. Doxorubicin cardiotoxicity: possible role of digoxin in its prevention. Br Med J. 1977 Dec 3;2(6100):1447–1449. doi: 10.1136/bmj.2.6100.1447. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Henderson I. C., Frei E., 3rd Adriamycin cardiotoxicity. Am Heart J. 1980 May;99(5):671–674. doi: 10.1016/0002-8703(80)90743-7. [DOI] [PubMed] [Google Scholar]
  40. Henderson I. C., Frei E., 3rd Testing for doxorubicin cardiotoxicity. N Engl J Med. 1979 Jun 14;300(24):1393–1394. [PubMed] [Google Scholar]
  41. Herman E., Ardalan B., Bier C., Waravdekar V., Krop S. Reduction of daunorubicin lethality and myocardial cellular alterations by pretreatment with ICRF-187 in Syrian golden hamsters. Cancer Treat Rep. 1979 Jan;63(1):89–92. [PubMed] [Google Scholar]
  42. Hopkins H. A., Betsill W. L., Jr, Hobson A. S., Looney W. B. Cyclophosphamide-induced cardiomyopathy in the rat. Cancer Treat Rep. 1982 Jul;66(7):1521–1527. [PubMed] [Google Scholar]
  43. Hutchinson R. J., Bailey C., Wood D., Donaldson M. H. Systolic time intervals in monitoring for anthracycline cardiomyopathy in pediatric patients. Cancer Treat Rep. 1978 Jun;62(6):907–910. [PubMed] [Google Scholar]
  44. Kishi T., Folkers K. Letter: Prevention by coenzyme Q10 (NSC-140865) of the inhibition by adriamycin (NSC-123127) of coenzyme Q10 enzymes. Cancer Treat Rep. 1976 Mar;60(3):223–4?U9ENG. [PubMed] [Google Scholar]
  45. Kishi T., Watanabe T., Folkers K. Bioenergetics in clinical medicine: prevention by forms of coenzyme Q of the inhibition by adriamycin of coenzyme Q10-enzymes in mitochondria of the myocardium. Proc Natl Acad Sci U S A. 1976 Dec;73(12):4653–4656. doi: 10.1073/pnas.73.12.4653. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Kosower E. M. A role for glutathione in muscle contraction. Experientia. 1970;26(7):760–761. doi: 10.1007/BF02232532. [DOI] [PubMed] [Google Scholar]
  47. Lambertenghi-Deliliers G., Zanon P. L., Pozzoli E. F., Bellini O. Myocardial injury induced by a single dose of adriamycin: an electron microscopic study. Tumori. 1976 Sep-Oct;62(5):517–528. doi: 10.1177/030089167606200506. [DOI] [PubMed] [Google Scholar]
  48. Lambertenghi-Deliliers G., Zanon P. L., Pozzoli E. F., Bellini O., Praga C. Ultrastructural alterations of atrial myocardium induced by adriamycin in chronically treated animals. Tumori. 1978 Feb 28;64(1):15–24. doi: 10.1177/030089167806400102. [DOI] [PubMed] [Google Scholar]
  49. Legha S. S., Benjamin R. S., Mackay B., Ewer M., Wallace S., Valdivieso M., Rasmussen S. L., Blumenschein G. R., Freireich E. J. Reduction of doxorubicin cardiotoxicity by prolonged continuous intravenous infusion. Ann Intern Med. 1982 Feb;96(2):133–139. doi: 10.7326/0003-4819-96-2-133. [DOI] [PubMed] [Google Scholar]
  50. Lehotay D. C., Levey B. A., Rogerson B. J., Levey G. S. Inhibition of cardiac guanylate cyclase by doxorubicin and some of its analogs: possible relationship to cardiotoxicity. Cancer Treat Rep. 1982 Feb;66(2):311–316. [PubMed] [Google Scholar]
  51. Lenaz L., Page J. A. Cardiotoxicity of adriamycin and related anthracyclines. Cancer Treat Rev. 1976 Sep;3(3):111–120. doi: 10.1016/s0305-7372(76)80018-7. [DOI] [PubMed] [Google Scholar]
  52. Levi-Schaffer F., Bernstein A., Meshorer A., Arnon R. Reduced toxicity of daunorubicin by conjugation to dextran. Cancer Treat Rep. 1982 Jan;66(1):107–114. [PubMed] [Google Scholar]
  53. Lewis A. B., Pilkington R., Takahashi M., Siegel S. E. Echocardiographic assessment of anthracycline cardiotoxicity in children. Med Pediatr Oncol. 1978;5(1):167–175. doi: 10.1002/mpo.2950050123. [DOI] [PubMed] [Google Scholar]
  54. Mason J. W. Anthracycline cardiotoxicity: recognition, management, and avoidance. Compr Ther. 1979 Jul;5(7):64–68. [PubMed] [Google Scholar]
  55. Mason J. W., Bristow M. R., Billingham M. E., Daniels J. R. Invasive and noninvasive methods of assessing adriamycin cardiotoxic effects in man: superiority of histopathologic assessment using endomyocardial biopsy. Cancer Treat Rep. 1978 Jun;62(6):857–864. [PubMed] [Google Scholar]
  56. Minow R. A., Benjamin R. S., Lee E. T., Gottlieb J. A. Adriamycin cardiomyopathy--risk factors. Cancer. 1977 Apr;39(4):1397–1402. doi: 10.1002/1097-0142(197704)39:4<1397::aid-cncr2820390407>3.0.co;2-u. [DOI] [PubMed] [Google Scholar]
  57. Minow R. A., Benjamin R. S., Lee E. T., Gottlieb J. A. QRS voltage change with adriamycin administration. Cancer Treat Rep. 1978 Jun;62(6):931–934. [PubMed] [Google Scholar]
  58. Morgan G. W., McIlveen B. M., Freedman A., Murray I. P. Radionuclide ejection fraction in doxorubicin cardiotoxicity. Cancer Treat Rep. 1981 Jul-Aug;65(7-8):629–638. [PubMed] [Google Scholar]
  59. Morganroth J., Chen C. C. Noninvasive diagnosis of the cardiomyopathies. Med Clin North Am. 1980 Jan;64(1):33–60. doi: 10.1016/s0025-7125(16)31624-8. [DOI] [PubMed] [Google Scholar]
  60. Mosijczuk A. D., Ruymann F. B., Mease A. D., Bernier R. D. Anthracycline cardiomyopathy in children: report of two cases. Cancer. 1979 Nov;44(5):1582–1587. doi: 10.1002/1097-0142(197911)44:5<1582::aid-cncr2820440507>3.0.co;2-h. [DOI] [PubMed] [Google Scholar]
  61. Myers C. E., McGuire W. P., Liss R. H., Ifrim I., Grotzinger K., Young R. C. Adriamycin: the role of lipid peroxidation in cardiac toxicity and tumor response. Science. 1977 Jul 8;197(4299):165–167. doi: 10.1126/science.877547. [DOI] [PubMed] [Google Scholar]
  62. Myers C. E., McGuire W., Young R. Adriamycin: amelioration of toxicity by alpha-tocopherol. Cancer Treat Rep. 1976 Jul;60(7):961–962. [PubMed] [Google Scholar]
  63. Olson H. M., Capen C. C. Subacute cardiotoxicity of adriamycin in the rat: biochemical and ultrastructural investigations. Lab Invest. 1977 Oct;37(4):386–394. [PubMed] [Google Scholar]
  64. Olson R. D., MacDonald J. S., vanBoxtel C. J., Boerth R. C., Harbison R. D., Slonim A. E., Freeman R. W., Oates J. A. Regulatory role of glutathione and soluble sulfhydryl groups in the toxicity of adriamycin. J Pharmacol Exp Ther. 1980 Nov;215(2):450–454. [PubMed] [Google Scholar]
  65. Parisi A. F., Moynihan P. F., Folland E. D. Echocardiographic evaluation of left ventricular function. Med Clin North Am. 1980 Jan;64(1):61–81. doi: 10.1016/s0025-7125(16)31625-x. [DOI] [PubMed] [Google Scholar]
  66. Praga C., Beretta G., Vigo P. L., Lenaz G. R., Pollini C., Bonadonna G., Canetta R., Castellani R., Villa E., Gallagher C. G. Adriamycin cardiotoxicity: a survey of 1273 patients. Cancer Treat Rep. 1979 May;63(5):827–834. [PubMed] [Google Scholar]
  67. Rahman A., Kessler A., More N., Sikic B., Rowden G., Woolley P., Schein P. S. Liposomal protection of adriamycin-induced cardiotoxicity in mice. Cancer Res. 1980 May;40(5):1532–1537. [PubMed] [Google Scholar]
  68. Rahman A., More N., Schein P. S. Doxorubicin-induced chronic cardiotoxicity and its protection by liposomal administration. Cancer Res. 1982 May;42(5):1817–1825. [PubMed] [Google Scholar]
  69. Sanyal S. K., Johnson W. W. Doxorubicin cardiomyopathy. Ann Intern Med. 1978 Jul;89(1):136–137. doi: 10.7326/0003-4819-89-1-136. [DOI] [PubMed] [Google Scholar]
  70. Savaraj N., Allen L. M., Sutton C., Troner M. Immunological modification of adriamycin cardiotoxicity. Res Commun Chem Pathol Pharmacol. 1980 Sep;29(3):549–559. [PubMed] [Google Scholar]
  71. Schell F. C., Yap H. Y., Blumenschein G., Valdivieso M., Bodey G. Potential cardiotoxicity with mitoxantrone. Cancer Treat Rep. 1982 Aug;66(8):1641–1643. [PubMed] [Google Scholar]
  72. Seraydarian M. W., Artaza L. Modification by adenosine of the effect of adriamycin on myocardial cells in culture. Cancer Res. 1979 Aug;39(8):2940–2944. [PubMed] [Google Scholar]
  73. Singer J. W., Narahara K. A., Ritchie J. L., Hamilton G. W., Kennedy J. W. Time- and dose-dependent changes in ejection fraction determined by radionuclide angiography after anthracycline therapy. Cancer Treat Rep. 1978 Jun;62(6):945–948. [PubMed] [Google Scholar]
  74. Steinherz L. J., Steinherz P. G., Mangiacasale D., Tan C., Miller D. R. Cardiac abnormalities after AMSA administration. Cancer Treat Rep. 1982 Mar;66(3):483–488. [PubMed] [Google Scholar]
  75. Suzuki T., Kanda H., Kawai Y., Tominaga K., Murata K. Cardiotoxicity of anthracycline antineoplastic drugs--Clinicopathological and experimental studies. Jpn Circ J. 1979 Nov;43(11):1000–1008. doi: 10.1253/jcj.43.1000. [DOI] [PubMed] [Google Scholar]
  76. Thayer W. S. Adriamycin stimulated superoxide formation in submitochondrial particles. Chem Biol Interact. 1977 Dec;19(3):265–278. doi: 10.1016/0009-2797(77)90050-3. [DOI] [PubMed] [Google Scholar]
  77. Ulmer H. E., Ludwig R., Geiger H. Assessment of adriamycin cardiotoxicity in children by systolic time intervals. Eur J Pediatr. 1979 Apr 25;131(1):21–31. doi: 10.1007/BF00442782. [DOI] [PubMed] [Google Scholar]
  78. Unverferth D. V., Magorien R. D., Leier C. V., Balcerzak S. P. Doxorubicin cardiotoxicity. Cancer Treat Rev. 1982 Jun;9(2):149–164. doi: 10.1016/s0305-7372(82)80014-5. [DOI] [PubMed] [Google Scholar]
  79. Van Vleet J. F., Ferrans V. J. Evaluation of vitamin E and selenium protection against chronic adriamycin toxicity in rabbits. Cancer Treat Rep. 1980 Feb-Mar;64(2-3):315–317. [PubMed] [Google Scholar]
  80. Van Vleet J. F., Ferrans V. J., Weirich W. E. Cardiac disease induced by chronic adriamycin administration in dogs and an evaluation of vitamin E and selenium as cardioprotectants. Am J Pathol. 1980 Apr;99(1):13–42. [PMC free article] [PubMed] [Google Scholar]
  81. Van Vleet J. F., Greenwood L., Ferrans V. J., Rebar A. H. Effect of selenium-vitamin E on adriamycin-induced cardiomyopathy in rabbits. Am J Vet Res. 1978 Jun;39(6):997–1010. [PubMed] [Google Scholar]
  82. Von Hoff D. D., Layard M. W., Basa P., Davis H. L., Jr, Von Hoff A. L., Rozencweig M., Muggia F. M. Risk factors for doxorubicin-induced congestive heart failure. Ann Intern Med. 1979 Nov;91(5):710–717. doi: 10.7326/0003-4819-91-5-710. [DOI] [PubMed] [Google Scholar]
  83. Von Hoff D. D., Layard M. Risk factors for development of daunorubicin cardiotoxicity. Cancer Treat Rep. 1981;65 (Suppl 4):19–23. [PubMed] [Google Scholar]
  84. Wagner H. N., Jr, Buchanan J. W. Radioactive tracers and the heart. Med Clin North Am. 1980 Jan;64(1):83–98. doi: 10.1016/s0025-7125(16)31626-1. [DOI] [PubMed] [Google Scholar]
  85. Wexler J. P., Blaufox M. D., Freeman L. M. Testing for doxorubicin cardiotoxicity. N Engl J Med. 1979 Jun 14;300(24):1393–1393. [PubMed] [Google Scholar]
  86. Woodman R. J., Cysyk R. L., Kline I., Gang M., Venditti J. M. Enhancement of the effectiveness of daunorubicin (NSC-82151) or adriamycin (NSC-123127) against early mouse L1210 leukemia with ICRF-159 (NSC-129943). Cancer Chemother Rep. 1975 Jul-Aug;59(4):689–695. [PubMed] [Google Scholar]

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