Evaluation of Demographic Parameters, Disease Burden, and Cardiovascular Risk Factors in Patients Who Received Primary Prophylaxis with Dexrazoxane for Prevention of Anthracycline-Induced Cardiotoxicity
Received Date : 22 Jan 2021
Accepted Date : 05 Jul 2021
Available Online : 16 Aug 2021
Doi: 10.37047/jos.2020-80963 - Article's Language: EN
J Oncol Sci. 2021;7(2):50-6
This is an open access article under the CC BY-NC-ND license
Objective: This retrospective study aimed to reveal the demographic parameters, disease burden, and cardiovascular risk factors in patients who received primary prophylaxis with dexrazoxane for the prevention of anthracycline-induced cardiotoxicity. We also evaluated the compliance of dexrazoxane use as per the American Society of Clinical Oncology (ASCO) Clinical Practice Guideline (CPG) criteria in these patients. Material and Methods: Data of 44 patients were retrospectively analyzed. A data registration form comprising 31 questions, including demographic characteristics, anthracycline treatment and dosage, chemotherapeutic agents, radiotherapy, surgical procedures, and data on cardiac functions and cardiovascular risk parameters, were retrospectively analyzed for each patient included in the study. Results: The average age of patients was 53 years, and the percentage of female patients was 88.6%, among which, the primary diagnosis was breast cancer. In 32 of 44 patients, no oncological treatment was administered before the anthracycline treatment. In all 44 patients, the ejection fraction value before anthracycline treatment was 60% or higher. Eleven patients received cumulative high-dose anthracycline treatment (doxorubicin ≥250 mg/m2, epirubicin ≥600 mg/m2). As per the recommendations of the ASCO CPG, 77.2% of patients in the study population were at high risk for the development of cardiac dysfunction. For 22.8% of the patients, the guideline recommendation for the development of cardiac dysfunction did not exist. Six of these ten patients, which are not considered to be at high risk for developing cardiac dysfunction, had at least one of the cardiovascular risk factors: smoking, hypertension, diabetes, dyslipidemia, or obesity. Conclusion: Cardiotoxicity of anthracyclines is dose-dependent and can occur at any time in the treatment course with acute, subacute, and late-onset presentations. Cardiotoxicity of anthracyclines is one of its most serious adverse effects though occasionally, precluding its usage even in potentially curative cases. Co-administration of dexrazoxane has been shown to reduce cardiotoxicity effectively. Further studies on the use of dexrazoxane in patients who are not in the high-risk group for anthracycline-induced cardiotoxicity are warranted.
  1. Valcovici M, Andrica F, Serban C, Dragan S. Cardiotoxicity of anthracycline therapy: current perspectives. Arch Med Sci. 2016;12(2):428-435. [Crossref]  [PubMed]  [PMC] 
  2. Bansal N, Akam-Venkata J, Franco VI, Lipshultz SE. Heart Failure in Pediatric Oncologic Disease. In: Jefferies JL, Chang AC, Rossano JW, Shaddy RE, Towbin JA, eds. Heart Failure in the Child and Young Adult (from Bench to Bedside). 1st ed. London, United Kingdom: Elsevier/Academic Press; 2018. p.425-443. [Crossref]  [PubMed]  [PMC] 
  3. McGowan JV, Chung R, Maulik A, Piotrowska I, Walker JM, Yellon DM. Anthracycline chemotherapy and cardiotoxicity. Cardiovasc Drugs Ther. 2017;31(1):63-75. [Crossref]  [PubMed]  [PMC] 
  4. Salmon SE. Chemotherapeutic agents: cancer chemotherapy. In: Myers FH, Jawetz E, Goldfien A, eds. Review of Medical Pharmacology. 7th ed. Los Altos, CA: Lange; 1980. 477-513. [Link] 
  5. Gewirtz DA. A critical evaluation of the mechanisms of action proposed for the antitumor effects of the anthracycline antibiotics adriamycin and daunorubicin. Biochem Pharmacol. 1999;57(7):727-741. [Crossref]  [PubMed] 
  6. Raj S, Franco VI, Lipshultz SE. Anthracycline-induced cardiotoxicity: a review of pathophysiology, diagnosis, and treatment. Curr Treat Options Cardiovasc Med. 2014;16(6):315. [Crossref]  [PubMed] 
  7. Vivenza D, Feola M, Garrone O, Monteverde M, Merlano M, Lo Nigro C. Role of the renin-angiotensin-aldosterone system and the glutathione S-transferase Mu, Pi and Theta gene polymorphisms in cardiotoxicity after anthracycline chemotherapy for breast carcinoma. Int J Biol Markers. 2013;28(4):e336-347. [Crossref]  [PubMed] 
  8. Chatterjee K, Zhang J, Honbo N, Karliner JS. Doxorubicin cardiomyopathy. Cardiology. 2010;115(2):155-162. d [Crossref]  [PubMed]  [PMC] 
  9. Appel JM, Sander K, Hansen PB, Møller JE, Krarup-Hansen A, Gustafsson F. Left ventricular assist device as bridge to recovery for anthracycline-induced terminal heart failure. Congest Heart Fail. 2012;18(5):291-294. [Crossref]  [PubMed] 
  10. Scott JM, Khakoo A, Mackey JR, Haykowsky MJ, Douglas PS, Jones LW. Modulation of anthracycline-induced cardiotoxicity by aerobic exercise in breast cancer: current evidence and underlying mechanisms. Circulation. 2011;124(5):642-650. [Crossref]  [PubMed]  [PMC] 
  11. Armenian SH, Lacchetti C, Lenihan D. Prevention and Monitoring of Cardiac Dysfunction in Survivors of Adult Cancers: American Society of Clinical Oncology Clinical Practice Guideline Summary. J Oncol Pract. 2017;13(4):270-275. [Crossref]  [PubMed] 
  12. Asselin BL, Devidas M, Chen L, et al. Cardioprotection and Safety of Dexrazoxane in Patients Treated for Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia or Advanced-Stage Lymphoblastic Non-Hodgkin Lymphoma: A Report of the Children's Oncology Group Randomized Trial Pediatric Oncology Group 9404. J Clin Oncol. 2016;34(8):854-62. Erratum in: J Clin Oncol. 2017; 35(18): 2100. [Crossref]  [PubMed]  [PMC] 
  13. Swain SM, Whaley FS, Gerber MC, et al. Cardioprotection with dexrazoxane for doxorubicin-containing therapy in advanced breast cancer. J Clin Oncol. 1997;15(4):1318-1332. [Crossref]  [PubMed] 
  14. Tahover E, Segal A, Isacson R, et al. Dexrazoxane added to doxorubicin-based adjuvant chemotherapy of breast cancer: a retrospective cohort study with a comparative analysis of toxicity and survival. Anticancer Drugs. 2017;28(7):787-794. [Crossref]  [PubMed] 
  15. Bergmann O, Bhardwaj RD, Bernard S, et al. Evidence for cardiomyocyte renewal in humans. Science. 2009;324(5923):98-102. [Crossref]  [PubMed]  [PMC] 
  16. Reichardt P, Tabone MD, Mora J, Morland B, Jones RL. Risk-benefit of dexrazoxane for preventing anthracycline-related cardiotoxicity: re-evaluating the European labeling. Future Oncol. 2018;14(25):2663-2676. [Crossref]  [PubMed] 
  17. Murtagh G, Lyons T, O'Connell E, et al. Late cardiac effects of chemotherapy in breast cancer survivors treated with adjuvant doxorubicin: 10-year follow-up. Breast Cancer Res Treat. 2016;156(3):501-506. [Crossref]  [PubMed]