Prevention of Heart Failure Induced by Doxorubicin With Early Administration of Dexrazoxane

Summary

The purpose of this research study is to determine whether early administration of Dexrazoxane prevents Doxorubicin induced cardiotoxicity.

Timeline

Start

2021-09-14

Primary completion

2024-06-11

Completion

2025-06-11

Publications

• Background Chang HM, Moudgil R, Scarabelli T, Okwuosa TM, Yeh ETH. Cardiovascular Complications of Cancer Therapy: Best Practices in Diagnosis, Prevention, and Management: Part 1. J Am Coll Cardiol. 2017 Nov 14;70(20):2536-2551. doi: 10.1016/j.jacc.2017.09.1096.
• Background Zhang S, Liu X, Bawa-Khalfe T, Lu LS, Lyu YL, Liu LF, Yeh ET. Identification of the molecular basis of doxorubicin-induced cardiotoxicity. Nat Med. 2012 Nov;18(11):1639-42. doi: 10.1038/nm.2919. Epub 2012 Oct 28.
• Background Lipshultz SE, Lipsitz SR, Kutok JL, Miller TL, Colan SD, Neuberg DS, Stevenson KE, Fleming MD, Sallan SE, Franco VI, Henkel JM, Asselin BL, Athale UH, Clavell LA, Michon B, Laverdiere C, Larsen E, Kelly KM, Silverman LB. Impact of hemochromatosis gene mutations on cardiac status in doxorubicin-treated survivors of childhood high-risk leukemia. Cancer. 2013 Oct 1;119(19):3555-62. doi: 10.1002/cncr.28256. Epub 2013 Jul 16.
• Background Tewey KM, Rowe TC, Yang L, Halligan BD, Liu LF. Adriamycin-induced DNA damage mediated by mammalian DNA topoisomerase II. Science. 1984 Oct 26;226(4673):466-8. doi: 10.1126/science.6093249.
• Background Olson LE, Bedja D, Alvey SJ, Cardounel AJ, Gabrielson KL, Reeves RH. Protection from doxorubicin-induced cardiac toxicity in mice with a null allele of carbonyl reductase 1. Cancer Res. 2003 Oct 15;63(20):6602-6.
• Background Azuma Y, Arnaoutov A, Dasso M. SUMO-2/3 regulates topoisomerase II in mitosis. J Cell Biol. 2003 Nov 10;163(3):477-87. doi: 10.1083/jcb.200304088. Epub 2003 Nov 3.
• Background Lyu YL, Kerrigan JE, Lin CP, Azarova AM, Tsai YC, Ban Y, Liu LF. Topoisomerase IIbeta mediated DNA double-strand breaks: implications in doxorubicin cardiotoxicity and prevention by dexrazoxane. Cancer Res. 2007 Sep 15;67(18):8839-46. doi: 10.1158/0008-5472.CAN-07-1649.
• Background Swain SM, Whaley FS, Gerber MC, Weisberg S, York M, Spicer D, Jones SE, Wadler S, Desai A, Vogel C, Speyer J, Mittelman A, Reddy S, Pendergrass K, Velez-Garcia E, Ewer MS, Bianchine JR, Gams RA. Cardioprotection with dexrazoxane for doxorubicin-containing therapy in advanced breast cancer. J Clin Oncol. 1997 Apr;15(4):1318-32. doi: 10.1200/JCO.1997.15.4.1318.
• Background Bluethmann SM, Mariotto AB, Rowland JH. Anticipating the "Silver Tsunami": Prevalence Trajectories and Comorbidity Burden among Older Cancer Survivors in the United States. Cancer Epidemiol Biomarkers Prev. 2016 Jul;25(7):1029-36. doi: 10.1158/1055-9965.EPI-16-0133.
• Background Chang HM, Okwuosa TM, Scarabelli T, Moudgil R, Yeh ETH. Cardiovascular Complications of Cancer Therapy: Best Practices in Diagnosis, Prevention, and Management: Part 2. J Am Coll Cardiol. 2017 Nov 14;70(20):2552-2565. doi: 10.1016/j.jacc.2017.09.1095.
• Background Armstrong GT, Kawashima T, Leisenring W, Stratton K, Stovall M, Hudson MM, Sklar CA, Robison LL, Oeffinger KC. Aging and risk of severe, disabling, life-threatening, and fatal events in the childhood cancer survivor study. J Clin Oncol. 2014 Apr 20;32(12):1218-27. doi: 10.1200/JCO.2013.51.1055. Epub 2014 Mar 17.
• Background Darby SC, Cutter DJ, Boerma M, Constine LS, Fajardo LF, Kodama K, Mabuchi K, Marks LB, Mettler FA, Pierce LJ, Trott KR, Yeh ET, Shore RE. Radiation-related heart disease: current knowledge and future prospects. Int J Radiat Oncol Biol Phys. 2010 Mar 1;76(3):656-65. doi: 10.1016/j.ijrobp.2009.09.064.
• Background Swain SM, Vici P. The current and future role of dexrazoxane as a cardioprotectant in anthracycline treatment: expert panel review. J Cancer Res Clin Oncol. 2004 Jan;130(1):1-7. doi: 10.1007/s00432-003-0498-7. Epub 2003 Oct 17.
• Background Yeh ET, Chang HM. Oncocardiology-Past, Present, and Future: A Review. JAMA Cardiol. 2016 Dec 1;1(9):1066-1072. doi: 10.1001/jamacardio.2016.2132.
• Background Tan C, Tasaka H, Yu KP, Murphy ML, Karnofsky DA. Daunomycin, an antitumor antibiotic, in the treatment of neoplastic disease. Clinical evaluation with special reference to childhood leukemia. Cancer. 1967 Mar;20(3):333-53. doi: 10.1002/1097-0142(1967)20:33.0.co;2-k. No abstract available.
• Background Von Hoff DD, Layard MW, Basa P, Davis HL Jr, Von Hoff AL, Rozencweig M, Muggia FM. Risk factors for doxorubicin-induced congestive heart failure. Ann Intern Med. 1979 Nov;91(5):710-7. doi: 10.7326/0003-4819-91-5-710.
• Background Doroshow JH. Effect of anthracycline antibiotics on oxygen radical formation in rat heart. Cancer Res. 1983 Feb;43(2):460-72.
• Background Doroshow JH, Locker GY, Myers CE. Enzymatic defenses of the mouse heart against reactive oxygen metabolites: alterations produced by doxorubicin. J Clin Invest. 1980 Jan;65(1):128-35. doi: 10.1172/JCI109642.
• Background Doroshow JH. Doxorubicin-induced cardiac toxicity. N Engl J Med. 1991 Mar 21;324(12):843-5. doi: 10.1056/NEJM199103213241210. No abstract available.
• Background Gianni L, Herman EH, Lipshultz SE, Minotti G, Sarvazyan N, Sawyer DB. Anthracycline cardiotoxicity: from bench to bedside. J Clin Oncol. 2008 Aug 1;26(22):3777-84. doi: 10.1200/JCO.2007.14.9401.
• Background Herman EH, Ferrans VJ, Myers CE, Van Vleet JF. Comparison of the effectiveness of (+/-)-1,2-bis(3,5-dioxopiperazinyl-1-yl)propane (ICRF-187) and N-acetylcysteine in preventing chronic doxorubicin cardiotoxicity in beagles. Cancer Res. 1985 Jan;45(1):276-81.
• Background Myers C, Bonow R, Palmeri S, Jenkins J, Corden B, Locker G, Doroshow J, Epstein S. A randomized controlled trial assessing the prevention of doxorubicin cardiomyopathy by N-acetylcysteine. Semin Oncol. 1983 Mar;10(1 Suppl 1):53-5. No abstract available.
• Background Martin E, Thougaard AV, Grauslund M, Jensen PB, Bjorkling F, Hasinoff BB, Tjornelund J, Sehested M, Jensen LH. Evaluation of the topoisomerase II-inactive bisdioxopiperazine ICRF-161 as a protectant against doxorubicin-induced cardiomyopathy. Toxicology. 2009 Jan 8;255(1-2):72-9. doi: 10.1016/j.tox.2008.10.011. Epub 2008 Oct 25.
• Background Capranico G, Tinelli S, Austin CA, Fisher ML, Zunino F. Different patterns of gene expression of topoisomerase II isoforms in differentiated tissues during murine development. Biochim Biophys Acta. 1992 Aug 17;1132(1):43-8. doi: 10.1016/0167-4781(92)90050-a.
• Background Wang J, Zhang S, Rabinovich B, Bidaut L, Soghomonyan S, Alauddin MM, Bankson JA, Shpall E, Willerson JT, Gelovani JG, Yeh ET. Human CD34+ cells in experimental myocardial infarction: long-term survival, sustained functional improvement, and mechanism of action. Circ Res. 2010 Jun 25;106(12):1904-11. doi: 10.1161/CIRCRESAHA.110.221762. Epub 2010 May 6.
• Background Hasinoff BB. Chemistry of dexrazoxane and analogues. Semin Oncol. 1998 Aug;25(4 Suppl 10):3-9.
• Results Chang HM, Hsu JY, Ahn C, Yeh ETH. Prevention of Heart Failure Induced by Doxorubicin with Early Administration of Dexrazoxane (PHOENIX Study): dose response and time course of dexrazoxane-induced degradation of topoisomerase 2b. Cardiooncology. 2025 May 2;11(1):42. doi: 10.1186/s40959-025-00339-0.

Drugs

Indications

No indication recorded.