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

Barbara L. Asselin, Meenakshi Devidas, Lu Chen, Vivian I. Franco, Jeanette Pullen, Michael J Borowitz, Robert E. Hutchison, Yaddanapudi Ravindranath, Saro H. Armenian, Bruce M. Camitta, Steven E. Lipshultz

Research output: Contribution to journalArticle

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/m2 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.

Original languageEnglish (US)
Pages (from-to)854-862
Number of pages9
JournalJournal of Clinical Oncology
Volume34
Issue number8
DOIs
StatePublished - Mar 10 2016

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Dexrazoxane
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
Non-Hodgkin's Lymphoma
Doxorubicin
Pediatrics
Safety
Second Primary Neoplasms
Drug Therapy
Poisons
Anthracyclines
Left Ventricular Function
Disease-Free Survival

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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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. / Asselin, Barbara L.; Devidas, Meenakshi; Chen, Lu; Franco, Vivian I.; Pullen, Jeanette; Borowitz, Michael J; Hutchison, Robert E.; Ravindranath, Yaddanapudi; Armenian, Saro H.; Camitta, Bruce M.; Lipshultz, Steven E.

In: Journal of Clinical Oncology, Vol. 34, No. 8, 10.03.2016, p. 854-862.

Research output: Contribution to journalArticle

Asselin, Barbara L. ; Devidas, Meenakshi ; Chen, Lu ; Franco, Vivian I. ; Pullen, Jeanette ; Borowitz, Michael J ; Hutchison, Robert E. ; Ravindranath, Yaddanapudi ; Armenian, Saro H. ; Camitta, Bruce M. ; Lipshultz, Steven E. / 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. In: Journal of Clinical Oncology. 2016 ; Vol. 34, No. 8. pp. 854-862.
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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/m2 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.",
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T1 - Cardioprotection and safety of dexrazoxane in patients treated for newly diagnosed T-cell acute lymphoblastic leukemia or advanced-stage lymphoblastic non-Hodgkin lymphoma

T2 - A report of the Children's Oncology Group randomized trial Pediatric Oncology Group 9404

AU - Asselin, Barbara L.

AU - Devidas, Meenakshi

AU - Chen, Lu

AU - Franco, Vivian I.

AU - Pullen, Jeanette

AU - Borowitz, Michael J

AU - Hutchison, Robert E.

AU - Ravindranath, Yaddanapudi

AU - Armenian, Saro H.

AU - Camitta, Bruce M.

AU - Lipshultz, Steven E.

PY - 2016/3/10

Y1 - 2016/3/10

N2 - Purpose: To determine the oncologic efficacy, cardioprotective effectiveness, and safety of dexrazoxane added to chemotherapy that included a cumulative doxorubicin dose of 360 mg/m2 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.

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