Doxorubicin Administration by Continuous Infusion Is Not Cardioprotective: The Dana-Farber 91-01 Acute Lymphoblastic Leukemia Protocol

Lipshultz, Steven E.; Giantris, Amy; Lipsitz, Stuart R.; Dalton, Virginia; Asselin, Barbara L.; Barr, Ronald D.; Clavell, Luis A.; Hurwitz, Craig A.; Moghrabi, Albert; Samson, Yvan; Schorin, Marshall A.; Gelber, Richard D.; Sallan, Stephen E.; Colan, Steven D.

doi:10.1200/jco.2002.20.6.1677

Cited by 128 publications

(71 citation statements)

References 18 publications

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“…Eligibility criteria were specified in all cases although only partially in one trial. Details of whether outcome assessors were blinded to treatment allocation was adequate in two trials (Lipshultz et al, 2002(Lipshultz et al, , 2004; patient blinding to treatment allocation was unknown (Steinhertz et al, 1993;Iarussi et al, 1994;Lipshultz et al, 2002) or inadequate (Lipshultz et al, 2004). Results were adequately presented with point estimates and a measure of variability in two trials (Iarussi et al, 1994;Lipshultz et al, 2004) and an intention-to-treat analysis in one (Iarussi et al, 1994).…”

Section: Quantity and Quality Of Researchmentioning

confidence: 99%

“…Each considered a different cardioprotective intervention; two considered continuous infusion vs rapid (bolus) infusion, one each of doxorubicin (Lipshultz et al, 2002) and daunorubicin (Steinhertz et al, 1993), and two considered cardioprotective agents, one each of coenzyme Q10 (Iarussi et al, 1994) and dexrazoxane (Lipshultz et al, 2004). No cost-effectiveness studies considering cardioprotection in children receiving anthracycline therapy for cancer were identified.…”

Section: Quantity and Quality Of Researchmentioning

confidence: 99%

“…et al, 1993) This pilot study compared the antileukaemic efficacy of continuous infusion of daunorubicin with bolus infusion in children with newly diagnosed acute lymphoblastic leukaemia and reported cardiac function in a subgroup of patients. Less sophisticated echocardiographic techniques were used than in the study described above (Lipshultz et al, 2002). A median change in left ventricular fractional shortening of À6.5 units is reported for participants who received a bolus infusion of daunorubicin and þ 1 unit in those receiving the continuous infusion of daunorubicin (see Table 3).…”

Section: Assessment Of Effectivenessmentioning

confidence: 99%

“…Of 994 titles and abstracts, four randomised controlled trials met the inclusion criteria (Steinhertz et al, 1993;Iarussi et al, 1994;Lipshultz et al, 2002Lipshultz et al, , 2004) (see Table 1). Each considered a different cardioprotective intervention; two considered continuous infusion vs rapid (bolus) infusion, one each of doxorubicin (Lipshultz et al, 2002) and daunorubicin (Steinhertz et al, 1993), and two considered cardioprotective agents, one each of coenzyme Q10 (Iarussi et al, 1994) and dexrazoxane (Lipshultz et al, 2004).…”

Section: Quantity and Quality Of Researchmentioning

confidence: 99%

“…Continuous infusion vs bolus infusion of Doxorubicin (Lipshultz et al, 2002) This study looked at moderate dose doxorubicin administration by continuous infusion (48 h) or by bolus infusion in children with newly diagnosed acute lymphoblastic leukaemia and was designed to detect a reduction in toxicity. After doxorubicin treatment, no significant difference was demonstrated between the two groups for any cardiac characteristic measured (see Table 3).…”

Section: Assessment Of Effectivenessmentioning

confidence: 99%

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Clinical and cost-effectiveness of cardioprotection against the toxic effects of anthracyclines given to children with cancer: a systematic review

et al. 2007

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This review systematically assessed the evidence on the clinical and cost-effectiveness of cardioprotection against the toxic effects of anthracyclines given to children with cancer. We searched eight electronic databases, including Medline and the Cochrane Library, from inception to January 2006 for systematic reviews and randomised controlled trials that reported death, heart failure, arrhythmias or measures of cardiac performance associated with cardioprotective technologies compared with standard treatment in children treated for cancer with anthracyclines. Economic evaluations were also sought. Inclusion criteria, data extraction and quality assessment were undertaken by standard methodology. Four randomised controlled trials met the inclusion criteria of the review; each had methodological limitations. No economic evaluations were identified. Studies were combined through narrative synthesis. One trial found that continuous infusion of doxorubicin did not offer any cardioprotection over rapid infusion. One suggested that continuous infusion of daunorubicin provoked less cardiotoxicity than rapid infusion. One concluded that dexrazoxane reduces cardiac injury during doxorubicin therapy and one reported a protective effect of coenzyme Q 10 on cardiac function during anthracycline therapy. The evidence on the effectiveness of cardioprotective technologies in children is limited in quality and quantity thus making conclusions difficult. This is surprising given the importance of anthracycline use in children with cancer. Further long-term research, which includes relevant outcome measures, is needed to determine whether technologies influence the development of cardiac damage without limiting the antitumour efficacy of anthracyclines.

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