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    Continuous Versus Bolus Infusion of Doxorubicin in Children With ALL: Long-term Cardiac Outcomes

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    Authors
    Lipshultz, Steven E.
    Miller, Tracie L.
    Lipsitz, Stuart R.
    Neuberg, Donna S.
    Dahlberg, Suzanne E.
    Colan, Steven D.
    Silverman, Lewis B.
    Henkel, Jacqueline M.
    Franco, Vivian L.
    Cushman, Laura L.
    Asselin, Barbara L.
    Clavell, Luis A.
    Athale, Uma
    Michon, Bruno
    Laverdiere, Caroline
    Schorin, Marshall A.
    Larsen, Eric
    Usmani, G. Naheed
    Sallan, Stephen E.
    Show allShow less
    UMass Chan Affiliations
    Department of Pediatrics
    Document Type
    Journal Article
    Publication Date
    2012-12-01
    Keywords
    Adolescent
    Antibiotics, Antineoplastic
    Cancer Care Facilities
    Cardiomyopathies
    Cardiotoxins
    Child
    Child, Preschool
    Disease-Free Survival
    Dose-Response Relationship, Drug
    Doxorubicin
    Drug Administration Schedule
    Echocardiography
    Female
    Follow-Up Studies
    Heart Ventricles
    Humans
    Infusions, Intravenous
    Male
    Precursor Cell Lymphoblastic Leukemia-Lymphoma
    Risk Factors
    United States
    Ventricular Function, Left
    Cardiology
    Hemic and Lymphatic Diseases
    Oncology
    Pediatrics
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    Link to Full Text
    http://dx.doi.org/10.1542/peds.2012-0727
    Abstract
    BACKGROUND AND OBJECTIVES: Doxorubicin, effective against many malignancies, is limited by cardiotoxicity. Continuous-infusion doxorubicin, compared with bolus-infusion, reduces early cardiotoxicity in adults. Its effectiveness in reducing late cardiotoxicity in children remains uncertain. We determined continuous-infusion doxorubicin cardioprotective efficacy in long-term survivors of childhood acute lymphoblastic leukemia (ALL). METHODS: The Dana-Farber Cancer Institute ALL Consortium Protocol 91-01 enrolled pediatric patients between 1991 and 1995. Newly diagnosed high-risk patients were randomly assigned to receive a total of 360 mg/m(2) of doxorubicin in 30 mg/m(2) doses every 3 weeks, by either continuous (over 48 hours) or bolus-infusion (within 15 minutes). Echocardiograms at baseline, during, and after doxorubicin therapy were blindly remeasured centrally. Primary outcomes were late left ventricular (LV) structure and function. RESULTS: A total of 102 children were randomized to each treatment group. We analyzed 484 serial echocardiograms from 92 patients (n = 49 continuous; n = 43 bolus) with >/=1 echocardiogram >/=3 years after assignment. Both groups had similar demographics and normal baseline LV characteristics. Cardiac follow-up after randomization (median, 8 years) showed changes from baseline within the randomized groups (depressed systolic function, systolic dilation, reduced wall thickness, and reduced mass) at 3, 6, and 8 years; there were no statistically significant differences between randomized groups. Ten-year ALL event-free survival rates did not differ between the 2 groups (continuous-infusion, 83% versus bolus-infusion, 78%; P = .24). CONCLUSIONS: In survivors of childhood high-risk ALL, continuous-infusion doxorubicin, compared with bolus-infusion, provided no long-term cardioprotection or improvement in ALL event-free survival, hence provided no benefit over bolus-infusion.
    Source
    Pediatrics. 2012 Dec;130(6):1003-11. doi: 10.1542/peds.2012-0727. Link to article on publisher's site
    DOI
    10.1542/peds.2012-0727
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/43687
    PubMed ID
    23166343
    Related Resources
    Link to Article in PubMed
    ae974a485f413a2113503eed53cd6c53
    10.1542/peds.2012-0727
    Scopus Count
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