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Cardioprotection and Safety of Dexrazoxane in Patients Treated for Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia or Advanced-Stage Lymphoblastic Non-Hodgkin Lymphoma: A Report of the Children's Oncology Group Randomized Trial Pediatric Oncology Group 9404. J Clin Oncol 2016 Mar 10;34(8):854-62 PMID: 26700126 PMCID: PMC4872007

Pubmed ID

26700126

DOI

10.1200/JCO.2015.60.8851

Abstract

PURPOSE: To determine the oncologic efficacy, cardioprotective effectiveness, and safety of dexrazoxane added to chemotherapy that included a cumulative doxorubicin dose of 360 mg/m(2) to treat children and adolescents with newly diagnosed T-cell acute lymphoblastic leukemia (T-ALL) or lymphoblastic non-Hodgkin lymphoma (L-NHL).

PATIENTS AND METHODS: Patients were treated on Pediatric Oncology Group Protocol POG 9404, which included random assignment to treatment with or without dexrazoxane given as a bolus infusion immediately before every dose of doxorubicin. Cardiac effects were assessed by echocardiographic measurements of left ventricular function and structure.

RESULTS: Of 573 enrolled patients, 537 were eligible, evaluable, and randomly assigned to an arm with or without dexrazoxane. The 5-year event-free survival (with standard error) did not differ between groups: 76.7% (2.7%) for the dexrazoxane group versus 76.0% (2.7%) for the doxorubicin-only group (P = .9). The frequencies of severe grade 3 or 4 hematologic toxicity, infection, CNS events, and toxic deaths were similar in both groups (P ranged from .26 to .64). Of 11 second malignancies, eight occurred in patients who received dexrazoxane (P = .17). The mean left ventricular fractional shortening, wall thickness, and thickness-to-dimension ratio z scores measured 3 years after diagnosis were worse in the doxorubicin-alone group (n = 55 per group; P ≤ .01 for all comparisons). Mean fractional shortening z scores measured 3.5 to 6.4 years after diagnosis remained diminished and were lower in the 21 patients who received doxorubicin alone than in the 31 patients who received dexrazoxane (-2.03 v -0.24; P ≤ .001).

CONCLUSION: Dexrazoxane was cardioprotective and did not compromise antitumor efficacy, did not increase the frequencies of toxicities, and was not associated with a significant increase in second malignancies with this doxorubicin-containing chemotherapy regimen. We recommend dexrazoxane as a cardioprotectant for children and adolescents who have malignancies treated with anthracyclines.

Author List

Asselin BL, Devidas M, Chen L, Franco VI, Pullen J, Borowitz MJ, Hutchison RE, Ravindranath Y, Armenian SH, Camitta BM, Lipshultz SE

Author

Bruce M. Camitta MD Clinical Professor in the Medicine department at Medical College of Wisconsin




Scopus

2-s2.0-84962523680   47 Citations

MESH terms used to index this publication - Major topics in bold

Antineoplastic Combined Chemotherapy Protocols
Cardiomyopathies
Cardiotonic Agents
Cardiotoxicity
Child
Dexrazoxane
Doxorubicin
Female
Humans
Male
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
Treatment Outcome
Troponin T
jenkins-FCD Prod-353 9ccd8489072cb19f5b9f808bb23ed672c582f41e