TY - JOUR
T1 - Continuous versus bolus infusion of doxorubicin in children with ALL
T2 - Long-term cardiac outcomes
AU - Lipshultz, Steven E.
AU - Miller, Tracie L.
AU - Lipsitz, Stuart R.
AU - Neuberg, Donna S.
AU - Dahlberg, Suzanne E.
AU - Colan, Steven D.
AU - Silverman, Lewis B.
AU - Henkel, Jacqueline M.
AU - Franco, Vivian I.
AU - Cushman, Laura L.
AU - Asselin, Barbara L.
AU - Clavell, Luis A.
AU - Athale, Uma
AU - Michon, Bruno
AU - Laverdière, Caroline
AU - Schorin, Marshall A.
AU - Larsen, Eric
AU - Usmani, Naheed
AU - Sallan, Stephen E.
PY - 2012/12
Y1 - 2012/12
N2 - BACKGROUND AND OBJECTIVES: Doxorubicin, effective against manymalignancies, 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/m2 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 (continuousinfusion, 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.
AB - BACKGROUND AND OBJECTIVES: Doxorubicin, effective against manymalignancies, 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/m2 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 (continuousinfusion, 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.
KW - Anthracycline
KW - Cardiotoxicity
KW - Doxorubicin
KW - Leukemia
KW - Pediatrics
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UR - http://www.scopus.com/inward/citedby.url?scp=84870555288&partnerID=8YFLogxK
U2 - 10.1542/peds.2012-0727
DO - 10.1542/peds.2012-0727
M3 - Article
C2 - 23166343
AN - SCOPUS:84870555288
VL - 130
SP - 1003
EP - 1011
JO - Pediatrics
JF - Pediatrics
SN - 0031-4005
IS - 6
ER -