Barbara L Asselin1, Meenakshi Devidas2, Lu Chen2, Vivian I Franco2, Jeanette Pullen2, Michael J Borowitz2, Robert E Hutchison2, Yaddanapudi Ravindranath2, Saro H Armenian2, Bruce M Camitta2, Steven E Lipshultz2. 1. Barbara L. Asselin, University of Rochester School of Medicine and Wilmot Cancer Institute, Rochester; Robert E. Hutchison, State University of New York Upstate Medical Center, Syracuse, NY; Meenakshi Devidas, Children's Oncology Group and University of Florida, Gainesville, FL; Lu Chen, Children's Oncology Group, Monrovia; Saro H. Armenian, City of Hope National Medical Center, Duarte, CA; Vivian I. Franco, Yaddanapudi Ravindranath, and Steven E. Lipshultz, Wayne State University School of Medicine and Children's Hospital of Michigan, Detroit, MI; Jeanette Pullen, University of Mississippi Medical Center and Children's Hospital, Jackson, MS; Michael J. Borowitz, Johns Hopkins University School of Medicine and Johns Hopkins Hospital, Baltimore, MD; and Bruce M. Camitta, Medical College of Wisconsin, Midwest Center for Cancer and Blood Disorders, Milwaukee, WI. barbara_asselin@urmc.rochester.edu. 2. Barbara L. Asselin, University of Rochester School of Medicine and Wilmot Cancer Institute, Rochester; Robert E. Hutchison, State University of New York Upstate Medical Center, Syracuse, NY; Meenakshi Devidas, Children's Oncology Group and University of Florida, Gainesville, FL; Lu Chen, Children's Oncology Group, Monrovia; Saro H. Armenian, City of Hope National Medical Center, Duarte, CA; Vivian I. Franco, Yaddanapudi Ravindranath, and Steven E. Lipshultz, Wayne State University School of Medicine and Children's Hospital of Michigan, Detroit, MI; Jeanette Pullen, University of Mississippi Medical Center and Children's Hospital, Jackson, MS; Michael J. Borowitz, Johns Hopkins University School of Medicine and Johns Hopkins Hospital, Baltimore, MD; and Bruce M. Camitta, Medical College of Wisconsin, Midwest Center for Cancer and Blood Disorders, Milwaukee, WI.
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: 77.2% (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.
RCT Entities:
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: 77.2% (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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