Late health outcomes after dexrazoxane treatment: A report from the Children's Oncology Group.

TitleLate health outcomes after dexrazoxane treatment: A report from the Children's Oncology Group.
Publication TypeJournal Article
Year of Publication2021
AuthorsChow EJ, Aplenc R, Vrooman LM, Doody DR, Huang Y-SV, Aggarwal S, Armenian SH, K Baker S, Bhatia S, Constine LS, Freyer DR, Kopp LM, Leisenring WM, Asselin BL, Schwartz CL, Lipshultz SE
JournalCancer
Date Published2021 Oct 13
ISSN1097-0142
Abstract

BACKGROUND: The objective of this study was to examine long-term outcomes among children newly diagnosed with cancer who were treated in dexrazoxane-containing clinical trials.

METHODS: P9404 (acute lymphoblastic leukemia/lymphoma [ALL]), P9425 and P9426 (Hodgkin lymphoma), P9754 (osteosarcoma), and Dana-Farber Cancer Institute 95-01 (ALL) enrolled 1308 patients between 1996 and 2001: 1066 were randomized (1:1) to doxorubicin with or without dexrazoxane, and 242 (from P9754) were nonrandomly assigned to receive dexrazoxane. Trial data were linked with the National Death Index, the Organ Procurement and Transplantation Network, the Pediatric Health Information System (PHIS), and Medicaid. Osteosarcoma survivors from the Childhood Cancer Survivor Study (CCSS; n = 495; no dexrazoxane) served as comparators in subanalyses. Follow-up events were assessed with cumulative incidence, Cox regression, and Fine-Gray methods.

RESULTS: In randomized trials (cumulative prescribed doxorubicin dose, 100-360 mg/m ; median follow-up, 18.6 years), dexrazoxane was not associated with relapse (hazard ratio [HR], 0.84; 95% confidence interval [CI], 0.63-1.13), second cancers (HR, 1.19; 95% CI, 0.62-2.30), all-cause mortality (HR, 1.07; 95% CI, 0.78-1.47), or cardiovascular mortality (HR, 1.45; 95% CI, 0.41-5.16). Among P9754 patients (all exposed to dexrazoxane; cumulative doxorubicin, 450-600 mg/m ; median follow-up, 16.6-18.4 years), no cardiovascular deaths or heart transplantation occurred. The 20-year heart transplantation rate among CCSS osteosarcoma survivors (mean doxorubicin, 377 ± 145 mg/m ) was 1.6% (vs 0% in P9754; P = .13). Among randomized patients, serious cardiovascular outcomes (cardiomyopathy, ischemic heart disease, and stroke) ascertained by PHIS/Medicaid occurred less commonly with dexrazoxane (5.6%) than without it (17.6%; P = .02), although cardiomyopathy rates alone did not differ (4.4% vs 8.1%; P = .35).

CONCLUSIONS: Dexrazoxane did not appear to adversely affect long-term mortality, event-free survival, or second cancer risk.

DOI10.1002/cncr.33974
Alternate JournalCancer
PubMed ID34644414
Grant List / / St. Baldrick's Foundation /
R01 CA211996 / CA / NCI NIH HHS / United States
U10 CA098413 / CA / NCI NIH HHS / United States
/ / American Lebanese Syrian Associated Charities /
U10 CA180886 / CA / NCI NIH HHS / United States
U24 CA55727 / CA / NCI NIH HHS / United States
UG1 CA189955 / CA / NCI NIH HHS / United States
P30 CA21765 / CA / NCI NIH HHS / United States
6243-13 / / Leukemia and Lymphoma Society /
U10 CA180899 / CA / NCI NIH HHS / United States
U10 CA095861 / CA / NCI NIH HHS / United States
U10 CA098543 / CA / NCI NIH HHS / United States