Doxorubicin cardiotoxicity in children: Reduced incidence of cardiac dysfunction associated with continuous-infusion schedules

Berrak, Su Gülsün; Ewer, Michael S.; Jaffe, Norman; Pearson, Peggy; Ried, Hubert L.; Zietz, Hallie; Benjamin, Robert S.

doi:10.3892/or.8.3.611

Cited by 26 publications

(24 citation statements)

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“…Prolonged infusions of anthracyclines are less cardiotoxic; 23,24 however, it had not been analysed whether the in vivo leukaemic cell kill is equivalent to short-term infusions. Therefore, in COALL 92, patients were randomized receiving a single dose of 36 mg/m 2 daunorubicin, either as a 1-h or a 24-h infusion in a therapeutic window, before the start of induction treatment.…”

Section: Discussionmentioning

confidence: 99%

Cooperative study group for childhood acute lymphoblastic leukaemia (COALL): long-term results of trials 82,85,89,92 and 97

et al. 2009

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In this study, the long-term outcome of 1818 patients treated in five consecutive clinical trials (the cooperative study group for childhood acute lymphoblastic leukaemia (COALL) 82, 85, 89, 92 and 97) from 24 cooperating centres in Germany is reported. The probability of event-free survival (pEFS) improved significantly from the first two trials conducted in the 1980s (COALL 82 and COALL 85) to the three trials conducted in the 1990s (COALL 89, 92 and 97) (P ¼ 0.001). Through all COALL studies, age X10 years and initial white blood cell count (WBC) X50 Â 10 9 /l and pro-B immunophenotype were of significant prognostic relevance. A refinement of risk assessment has been achieved by in vitro drug sensitivity testing in COALL 92 and 97. In patients with very sensitive leukaemic cells, therapy could be reduced without loss of efficacy. In COALL 97, a further improvement in risk stratification was gained by the molecular assessment of minimal residual disease (MRD) under treatment, which proved to have a superior prognostic effect when compared with in vitro drug sensitivity testing. Importantly, the gradual reduction in central nervous system (CNS) irradiation led to a decreased incidence of brain tumours as a second malignancy. In general, the prevention of treatmentrelated late effects will be one of the major issues in future studies. It remains to be shown whether prolonged infusions of anthracyclines, which have been implemented into the COALL studies after equal efficacy compared with short-time infusions was confirmed, will be associated with fewer cardiac late effects. Another way to prevent late effects may be a more refined risk assessment allowing for a reduction in cumulative treatment burden. A great challenge in the future will be to improve the overall treatment results, which very likely can only be achieved by the identification of molecularly defined subgroups to which novel, rational therapeutic strategies can be applied.

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Section: Discussionmentioning

confidence: 99%

Cooperative study group for childhood acute lymphoblastic leukaemia (COALL): long-term results of trials 82,85,89,92 and 97

et al. 2009

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“…Diese Wirkung ist allerdings noch nicht für alle Patientengruppen gesichert [44]. Längere Anthracyclininfusionszeiten sollen ebenfalls die Kardiotoxizität verringern [45][46][47][48][49]. Die zurzeit vielversprechendste prä-ventive Maßnahme scheint die anthracyclinbegleitende Gabe von Dexrazoxan, einem mit den Anthracyclinen verwandten Eisenchelator, zu sein.…”

Section: Präventionunclassified

Chemotherapeutikainduzierte Herzinsuffizienz

Paulides

Wojnowski²

2007

Med Klin

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“…A study in children treated with 60 mg/m 2 DOX over 24 h or 75 mg/m 2 over 72 h showed a reduced incidence of CHF (1 of 97 patients) compared with historical control patients treated with the bolus schedule (13% of patients with CHF) (Berrak et al, 2001). In contrast, in a trial of 240 children with acute lymphoblastic leukemia who were randomized to receive continuous (over 48 h) or bolus infusion of 30 mg/m 2 DOX every 3 weeks up to a median cumulative dose of 340 mg/m 2 , there was no compelling evidence of reduced incidence of dilated cardiomyopathy or left ventricular hypertrophy 1.5 years after leukemia diagnosis (Lipshultz et al, 2002a).…”

Section: Preventionmentioning

confidence: 99%

Anthracyclines: Molecular Advances and Pharmacologic Developments in Antitumor Activity and Cardiotoxicity

et al. 2004

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Doxorubicin cardiotoxicity in children: Reduced incidence of cardiac dysfunction associated with continuous-infusion schedules

Cited by 26 publications

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Cooperative study group for childhood acute lymphoblastic leukaemia (COALL): long-term results of trials 82,85,89,92 and 97

Cooperative study group for childhood acute lymphoblastic leukaemia (COALL): long-term results of trials 82,85,89,92 and 97

Chemotherapeutikainduzierte Herzinsuffizienz

Anthracyclines: Molecular Advances and Pharmacologic Developments in Antitumor Activity and Cardiotoxicity

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