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Kopp LM, Womer RB, Schwartz CL, et al. Effects of dexrazoxane on doxorubicin-related cardiotoxicity and second malignant neoplasms in children with osteosarcoma: a report from the Children's Oncology Group. Cardiooncology. 2019;5:15doi: 10.1186/s40959-019-0050-9.
Kopp, L. M., Womer, R. B., Schwartz, C. L., Ebb, D. H., Franco, V. I., Hall, D., Barkauskas, D. A., Krailo, M. D., Grier, H. E., Meyers, P. A., Wexler, L. H., Marina, N. M., Janeway, K. A., Gorlick, R., Bernstein, M. L., Lipshultz, S. E. (2019). Effects of dexrazoxane on doxorubicin-related cardiotoxicity and second malignant neoplasms in children with osteosarcoma: a report from the Children's Oncology Group. Cardio-oncology (London, England), 515. https://doi.org/10.1186/s40959-019-0050-9
Kopp, Lisa M, et al. "Effects of dexrazoxane on doxorubicin-related cardiotoxicity and second malignant neoplasms in children with osteosarcoma: a report from the Children's Oncology Group." Cardio-oncology (London, England) vol. 5 (2019): 15. doi: https://doi.org/10.1186/s40959-019-0050-9
Kopp LM, Womer RB, Schwartz CL, Ebb DH, Franco VI, Hall D, Barkauskas DA, Krailo MD, Grier HE, Meyers PA, Wexler LH, Marina NM, Janeway KA, Gorlick R, Bernstein ML, Lipshultz SE. Effects of dexrazoxane on doxorubicin-related cardiotoxicity and second malignant neoplasms in children with osteosarcoma: a report from the Children's Oncology Group. Cardiooncology. 2019 Oct 28;5:15. doi: 10.1186/s40959-019-0050-9. eCollection 2019. PMID: 32154021; PMCID: PMC7048050.
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Cardiooncology. 2019 Oct 28;5:15. doi: 10.1186/s40959-019-0050-9. eCollection 2019.

Effects of dexrazoxane on doxorubicin-related cardiotoxicity and second malignant neoplasms in children with osteosarcoma: a report from the Children's Oncology Group.

Cardio-oncology (London, England)

Lisa M Kopp, Richard B Womer, Cindy L Schwartz, David H Ebb, Vivian I Franco, David Hall, Donald A Barkauskas, Mark D Krailo, Holcombe E Grier, Paul A Meyers, Leonard H Wexler, Neyssa M Marina, Katherine A Janeway, Richard Gorlick, Mark L Bernstein, Steven E Lipshultz,

Affiliations

  1. 1Department of Epidemiology and Biostatistics, Mel and Enid Zuckerman College of Public Health, The University of Arizona, 1295 N Martin Ave. PO Box 245210, Tucson, AZ 85724 USA.
  2. 2University of Arizona Cancer Center, University of Arizona, Tucson, AZ USA.
  3. 3Children's Hospital of Philadelphia, Philadelphia, PA USA.
  4. Children's Hospital of Wisconsin, Medical College of Wisconsin, Milwaukee, WI USA.
  5. 5Department of Pediatric Hematology-Oncology, Massachusetts General Hospital, Boston, MA USA.
  6. 6Department of Pediatrics, University at Buffalo, Oishei Children's Hospital, Roswell Park Comprehensive Cancer Center, Buffalo, NY USA.
  7. 7Children's Oncology Group, Monrovia, CA USA.
  8. 8Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA USA.
  9. 9Dana-Farber Cancer Institute, Boston, MA USA.
  10. 10Memorial Sloan Kettering Cancer Center, New York, NY USA.
  11. 11Five Prime Therapeutics, Inc., South San Francisco, CA USA.
  12. 12MD Anderson Cancer Center, Houston, TX USA.
  13. 13IWK Health Centre, Halifax, Nova Scotia Canada.

PMID: 32154021 PMCID: PMC7048050 DOI: 10.1186/s40959-019-0050-9

Abstract

BACKGROUND: Dexrazoxane protects from lower-cumulative-dose doxorubicin cardiotoxicity, but the effect of dexrazoxane in children with sarcoma treated with higher-cumulative-dose doxorubicin is unknown.

METHODS: We evaluated children with osteosarcoma (OS) on two Children's Oncology Group trials with higher dose doxorubicin (375-600 mg/m

RESULTS: All children had normal left ventricular (LV) systolic function as measured by LV fractional shortening and no heart failure. The end-diastolic septal thickness

CONCLUSIONS: Dexrazoxane prevented LV dysfunction and heart failure in children with OS receiving higher dose doxorubicin. However, LV structural changes were not fully prevented, especially in girls. As a result, hearts become abnormally small for body size, resulting in higher LV stress. Dexrazoxane did not increase the risk of SMN. Dexrazoxane should be used in this population, particularly for girls, to mitigate anthracycline-induced cardiotoxicity.

TRIAL REGISTRATIONS: ClinicalTrials.gov: NCT00003937 (P9754) registered 1 Nov 1999, and NCT00023998 (AOST0121) registered 13 Sept 2001.

© The Author(s). 2019.

Keywords: Cardiotoxicity; Doxorubicin; Osteosarcoma; Pediatrics

Conflict of interest statement

Competing interestsL.K. is an employee of the contract research organization Covance. M.K. is a consultant for Merck. K.J. has received travel reimbursement from Loxo oncology. R.G. has received labor

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