Equivalence ratio for daunorubicin to doxorubicin in relation to late heart failure in survivors of childhood cancer

Elizabeth A.M. Feijen, Wendy M. Leisenring, Kayla L. Stratton, Kirsten K. Ness, Helena J.H. Van Der Pal, Huib N. Caron, Gregory Armstrong, Daniel M. Green, Melissa M. Hudson, Kevin C. Oeffinger, Leslie L. Robison, Marilyn Stovall, Leontien C.M. Kremer, Eric J. Chow

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Abstract

Purpose: Cumulative anthracycline dose is one of the strongest predictors of heart failure (HF) after cancer treatment. However, the differential risk for cardiotoxicity between daunorubicin and doxorubicin has not been rigorously evaluated among survivors of childhood cancer. These risks, which are based on hematologic toxicity, are currently assumed to be approximately equivalent. Patients and Methods: Data from 15,815 survivors of childhood cancer who survived at least 5 years were used. Survivors were from the Emma Children's Hospital/Academic Medical Center (n = 1,349), the National Wilms Tumor Study (n = 364), the St Jude Lifetime Cohort Study (n = 1,695), and the Childhood Cancer Survivor Study (n = 12,407). The hazard ratio (HR) for clinical HF through age 40 years for doses of daunorubicin and doxorubicin (per 100-mg/m2 increments) was estimated by using Cox regression adjusted for sex, age at diagnosis, treatment with other anthracycline agents and chest radiation, and cohort membership. Results: In total, 5,144 (32.5%) patients received doxorubicin as part of their cancer treatment, whereas 2,243 (14.7%) received daunorubicin. On the basis of 271 occurrences of HF during a median follow-up time after cohort entry of 17.3 years (range, 0.0 to 35.0 years), the cumulative incidence of HF at age 40 years was 3.2% (95% CI, 2.8% to 3.7%). The average ratio of HRs for daunorubicin to doxorubicin was 0.45 (95% CI, 0.23 to 0.73). A similar ratio was obtained by using a linear dose-response model, which yielded an HR of 0.49 (95% CI, 0.28 to 0.70). Conclusion: Compared with doxorubicin, daunorubicin was less cardiotoxic among survivors of childhood cancer than most current guidelines suggest. This may have implications for follow-up guidelines. The feasibility of substitution of doxorubicin with daunorubicin in childhood cancer treatment protocols to reduce cardiotoxicity should be additionally investigated.

Original languageEnglish (US)
Pages (from-to)3774-3780
Number of pages7
JournalJournal of Clinical Oncology
Volume33
Issue number32
DOIs
StatePublished - Nov 10 2015

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Daunorubicin
Doxorubicin
Survivors
Heart Failure
Neoplasms
Anthracyclines
Antineoplastic Protocols
Guidelines
Wilms Tumor
Cohort Studies
Thorax
Therapeutics
Radiation
Incidence

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Feijen, E. A. M., Leisenring, W. M., Stratton, K. L., Ness, K. K., Van Der Pal, H. J. H., Caron, H. N., ... Chow, E. J. (2015). Equivalence ratio for daunorubicin to doxorubicin in relation to late heart failure in survivors of childhood cancer. Journal of Clinical Oncology, 33(32), 3774-3780. https://doi.org/10.1200/JCO.2015.61.5187

Equivalence ratio for daunorubicin to doxorubicin in relation to late heart failure in survivors of childhood cancer. / Feijen, Elizabeth A.M.; Leisenring, Wendy M.; Stratton, Kayla L.; Ness, Kirsten K.; Van Der Pal, Helena J.H.; Caron, Huib N.; Armstrong, Gregory; Green, Daniel M.; Hudson, Melissa M.; Oeffinger, Kevin C.; Robison, Leslie L.; Stovall, Marilyn; Kremer, Leontien C.M.; Chow, Eric J.

In: Journal of Clinical Oncology, Vol. 33, No. 32, 10.11.2015, p. 3774-3780.

Research output: Contribution to journalArticle

Feijen, EAM, Leisenring, WM, Stratton, KL, Ness, KK, Van Der Pal, HJH, Caron, HN, Armstrong, G, Green, DM, Hudson, MM, Oeffinger, KC, Robison, LL, Stovall, M, Kremer, LCM & Chow, EJ 2015, 'Equivalence ratio for daunorubicin to doxorubicin in relation to late heart failure in survivors of childhood cancer', Journal of Clinical Oncology, vol. 33, no. 32, pp. 3774-3780. https://doi.org/10.1200/JCO.2015.61.5187
Feijen, Elizabeth A.M. ; Leisenring, Wendy M. ; Stratton, Kayla L. ; Ness, Kirsten K. ; Van Der Pal, Helena J.H. ; Caron, Huib N. ; Armstrong, Gregory ; Green, Daniel M. ; Hudson, Melissa M. ; Oeffinger, Kevin C. ; Robison, Leslie L. ; Stovall, Marilyn ; Kremer, Leontien C.M. ; Chow, Eric J. / Equivalence ratio for daunorubicin to doxorubicin in relation to late heart failure in survivors of childhood cancer. In: Journal of Clinical Oncology. 2015 ; Vol. 33, No. 32. pp. 3774-3780.
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abstract = "Purpose: Cumulative anthracycline dose is one of the strongest predictors of heart failure (HF) after cancer treatment. However, the differential risk for cardiotoxicity between daunorubicin and doxorubicin has not been rigorously evaluated among survivors of childhood cancer. These risks, which are based on hematologic toxicity, are currently assumed to be approximately equivalent. Patients and Methods: Data from 15,815 survivors of childhood cancer who survived at least 5 years were used. Survivors were from the Emma Children's Hospital/Academic Medical Center (n = 1,349), the National Wilms Tumor Study (n = 364), the St Jude Lifetime Cohort Study (n = 1,695), and the Childhood Cancer Survivor Study (n = 12,407). The hazard ratio (HR) for clinical HF through age 40 years for doses of daunorubicin and doxorubicin (per 100-mg/m2 increments) was estimated by using Cox regression adjusted for sex, age at diagnosis, treatment with other anthracycline agents and chest radiation, and cohort membership. Results: In total, 5,144 (32.5{\%}) patients received doxorubicin as part of their cancer treatment, whereas 2,243 (14.7{\%}) received daunorubicin. On the basis of 271 occurrences of HF during a median follow-up time after cohort entry of 17.3 years (range, 0.0 to 35.0 years), the cumulative incidence of HF at age 40 years was 3.2{\%} (95{\%} CI, 2.8{\%} to 3.7{\%}). The average ratio of HRs for daunorubicin to doxorubicin was 0.45 (95{\%} CI, 0.23 to 0.73). A similar ratio was obtained by using a linear dose-response model, which yielded an HR of 0.49 (95{\%} CI, 0.28 to 0.70). Conclusion: Compared with doxorubicin, daunorubicin was less cardiotoxic among survivors of childhood cancer than most current guidelines suggest. This may have implications for follow-up guidelines. The feasibility of substitution of doxorubicin with daunorubicin in childhood cancer treatment protocols to reduce cardiotoxicity should be additionally investigated.",
author = "Feijen, {Elizabeth A.M.} and Leisenring, {Wendy M.} and Stratton, {Kayla L.} and Ness, {Kirsten K.} and {Van Der Pal}, {Helena J.H.} and Caron, {Huib N.} and Gregory Armstrong and Green, {Daniel M.} and Hudson, {Melissa M.} and Oeffinger, {Kevin C.} and Robison, {Leslie L.} and Marilyn Stovall and Kremer, {Leontien C.M.} and Chow, {Eric J.}",
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T1 - Equivalence ratio for daunorubicin to doxorubicin in relation to late heart failure in survivors of childhood cancer

AU - Feijen, Elizabeth A.M.

AU - Leisenring, Wendy M.

AU - Stratton, Kayla L.

AU - Ness, Kirsten K.

AU - Van Der Pal, Helena J.H.

AU - Caron, Huib N.

AU - Armstrong, Gregory

AU - Green, Daniel M.

AU - Hudson, Melissa M.

AU - Oeffinger, Kevin C.

AU - Robison, Leslie L.

AU - Stovall, Marilyn

AU - Kremer, Leontien C.M.

AU - Chow, Eric J.

PY - 2015/11/10

Y1 - 2015/11/10

N2 - Purpose: Cumulative anthracycline dose is one of the strongest predictors of heart failure (HF) after cancer treatment. However, the differential risk for cardiotoxicity between daunorubicin and doxorubicin has not been rigorously evaluated among survivors of childhood cancer. These risks, which are based on hematologic toxicity, are currently assumed to be approximately equivalent. Patients and Methods: Data from 15,815 survivors of childhood cancer who survived at least 5 years were used. Survivors were from the Emma Children's Hospital/Academic Medical Center (n = 1,349), the National Wilms Tumor Study (n = 364), the St Jude Lifetime Cohort Study (n = 1,695), and the Childhood Cancer Survivor Study (n = 12,407). The hazard ratio (HR) for clinical HF through age 40 years for doses of daunorubicin and doxorubicin (per 100-mg/m2 increments) was estimated by using Cox regression adjusted for sex, age at diagnosis, treatment with other anthracycline agents and chest radiation, and cohort membership. Results: In total, 5,144 (32.5%) patients received doxorubicin as part of their cancer treatment, whereas 2,243 (14.7%) received daunorubicin. On the basis of 271 occurrences of HF during a median follow-up time after cohort entry of 17.3 years (range, 0.0 to 35.0 years), the cumulative incidence of HF at age 40 years was 3.2% (95% CI, 2.8% to 3.7%). The average ratio of HRs for daunorubicin to doxorubicin was 0.45 (95% CI, 0.23 to 0.73). A similar ratio was obtained by using a linear dose-response model, which yielded an HR of 0.49 (95% CI, 0.28 to 0.70). Conclusion: Compared with doxorubicin, daunorubicin was less cardiotoxic among survivors of childhood cancer than most current guidelines suggest. This may have implications for follow-up guidelines. The feasibility of substitution of doxorubicin with daunorubicin in childhood cancer treatment protocols to reduce cardiotoxicity should be additionally investigated.

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