Dose Equivalence Analysis Indicates Reduced Risk of Late Heart Failure With Daunorubicin vs Doxorubicin in Survivors of Childhood Cancer
In a study reported in the Journal of Clinical Oncology, Feijen et al found that daunorubicin may be associated with reduced risk of late heart failure vs doxorubicin in survivors of childhood cancer.
Study Details
The study included data from 15,815 survivors of childhood cancer who survived ≥ 5 years from the Emma Children’s Hospital/Academic Medical Center (n = 1,349), National Wilms Tumor Study (n = 364), St Jude Lifetime Cohort Study (n = 1,695), and Childhood Cancer Survivor Study (n =12,407). Hazard ratios (HRs) for clinical heart failure through age 40 years for daunorubicin and doxorubicin doses per 100 mg/m2 increments were estimated using Cox regression analysis adjusted for sex, age at diagnosis, treatment with other anthracyclines and chest radiation, and cohort.
Late Heart Failure Risk
In total, 5,144 (32.5%) patients received doxorubicin and 2,243 (14.7%) received daunorubicin. The cumulative incidence of heart failure was 3.2% on the basis of 271 cases during median follow-up of 17.3 years. The average equivalence ratio of hazard ratios for daunorubicin to doxorubicin was 0.45 (95% confidence interval [CI] = 0.23–0.73). Chest radiotherapy was a significant predictor of heart failure, but interactions between chest radiotherapy and doxorubicin (P = .09) and daunorubicin (P = .73) were not significant. A similar ratio of risk was obtained on analysis using a linear dose-response model (HR = 0.49, 95% CI = 0.28–0.70).
The investigators concluded: “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.”
Elizabeth A.M. Feijen, MSc, of Emma Children’s Hospital/Academic Medical Center, Amsterdam, is the corresponding author for the Journal of Clinical Oncology article.
The study was supported by the Foundation of Pediatric Cancer Research, Amsterdam, Dutch Cancer Society, Stichting Kinderen Kankervrij, National Cancer Institute, and American Lebanese-Syrian Associated Charities. For full disclosures of the study authors, visit jco.ascopubs.org.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
