TY - JOUR
T1 - Late health outcomes after dexrazoxane treatment
T2 - A report from the Children's Oncology Group
AU - Chow, Eric J.
AU - Aplenc, Richard
AU - Vrooman, Lynda M.
AU - Doody, David R.
AU - Huang, Yuan Shung V.
AU - Aggarwal, Sanjeev
AU - Armenian, Saro H.
AU - Baker, K. Scott
AU - Bhatia, Smita
AU - Constine, Louis S.
AU - Freyer, David R.
AU - Kopp, Lisa M.
AU - Leisenring, Wendy M.
AU - Asselin, Barbara L.
AU - Schwartz, Cindy L.
AU - Lipshultz, Steven E.
N1 - Funding Information:
Eric J. Chow reports support for attending meetings and/or travel from the Children's Oncology Group (COG) and chairmanship of the COG's Outcomes/Survivorship Committee. Louis S. Constine reports grants or contracts from the University of Alabama; royalties or licenses from UpToDate, Springer, and Wolters Kluwer; payments or honoraria from the American Society for Hematology and the University of Miami; and participation on a pediatric oncology board for the National Cancer Institute. Lisa M. Kopp is an employee of Arcus Biosciences and has stocks and stock options through Arcus Biosciences. Smita Bhatia reports institutional payments from the National Cancer Institute, the Leukemia & Lymphoma Society, and the V Foundation; honoraria for a grand rounds presentation; grant support for travel from the National Cancer Institute; membership on an advisory board for St. Jude Children's Hospital; and an associate editorship with the American Society of Clinical Oncology. Steven E. Lipshultz reports consulting fees from Clinigen. The other authors made no disclosures.
Funding Information:
Eric J. Chow reports support for attending meetings and/or travel from the Children's Oncology Group (COG) and chairmanship of the COG's Outcomes/Survivorship Committee. Louis S. Constine reports grants or contracts from the University of Alabama; royalties or licenses from UpToDate, Springer, and Wolters Kluwer; payments or honoraria from the American Society for Hematology and the University of Miami; and participation on a pediatric oncology board for the National Cancer Institute. Lisa M. Kopp is an employee of Arcus Biosciences and has stocks and stock options through Arcus Biosciences. Smita Bhatia reports institutional payments from the National Cancer Institute, the Leukemia & Lymphoma Society, and the V Foundation; honoraria for a grand rounds presentation; grant support for travel from the National Cancer Institute; membership on an advisory board for St. Jude Children's Hospital; and an associate editorship with the American Society of Clinical Oncology. Steven E. Lipshultz reports consulting fees from Clinigen. The other authors made no disclosures. This study was supported by the US National Institutes of Health (P30 CA21765, R01 CA211996, U10 CA098543, U10 CA098413, U10 CA180886, U10 CA180899, U10 CA095861, U24 CA55727, and UG1 CA189955), the St. Baldrick's Foundation, the Leukemia & Lymphoma Society, Sofia's Hope, Inc, and the American Lebanese Syrian Associated Charities.
Funding Information:
This study was supported by the US National Institutes of Health (P30 CA21765, R01 CA211996, U10 CA098543, U10 CA098413, U10 CA180886, U10 CA180899, U10 CA095861, U24 CA55727, and UG1 CA189955), the St. Baldrick's Foundation, the Leukemia & Lymphoma Society, Sofia's Hope, Inc, and the American Lebanese Syrian Associated Charities.
Publisher Copyright:
© 2021 American Cancer Society
PY - 2022/2/15
Y1 - 2022/2/15
N2 - 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/m2; 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/m2; 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/m2) 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.
AB - 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/m2; 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/m2; 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/m2) 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.
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U2 - 10.1002/cncr.33974
DO - 10.1002/cncr.33974
M3 - Article
AN - SCOPUS:85116936157
SN - 0008-543X
VL - 128
SP - 788
EP - 796
JO - Cancer
JF - Cancer
IS - 4
ER -