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

We retrospectively reviewed the medical records of 97 children (59 boys and 38 girls) with a median age of 13 +/- 4 years who had been treated with continuous infusion of doxorubicin at a dosage of 60 mg/m2 over 24 h (61 patients) or at a dosage of 75 mg/m2 over 72 h (36 patients). The drug was administered every 3 weeks. The cardiac status of patients was evaluated as a baseline and every 6 months during, and following therapy (median, 30.5 months). The evaluations included M-mode and two-dimensional echocardiography. Congestive heart failure developed in only one patient in this series, an 8-year-old girl who ultimately died of her cardiac complication. This incidence of doxorubicin-induced cardiotoxicity was compared with that seen in a control group of pediatric patients previously treated with doxorubicin at similar dosages but with a rapid infusion. The result compared favorably to the 13% incidence of cardiotoxicity (p = 0.03) and 7% mortality (p < 0.01) in the control group. No changes in the levels of tumor response were noted in children treated by continuous infusion when compared with historical controls. Continuous-infusion schedules of doxorubicin thus result in fewer incidences of cardiotoxicity in children and should be considered for wider application in pediatric cancer patients receiving doxorubicin.

Doxorubicin cardiotoxicity in children: comparison of a consecutive divided daily dose administration schedule with single dose (rapid) infusion administration.

BACKGROUND: Doxorubicin cardiotoxicity remains a serious problem in children with malignancy. The present study was undertaken to determine if the administration of consecutive divided daily doses of doxorubicin would significantly reduce the likelihood of cardiotoxicity in children compared with a single dose administration regimen. PROCEDURE: One hundred thirteen children (60 boys and 53 girls) received doxorubicin either by single dose infusion or by a consecutive divided daily dose schedule. The divided dose patients received one third of the total cycle dose over 20 minutes for 3 consecutive days. Patients treated according to a single dose schedule received the cycle dose as a 20-minute infusion. The mean doxorubicin dose was 341 mg/m2. Patients were followed up for 4-180 months. There were 60 boys and 53 girls in the series. RESULTS: Fifteen patients developed cardiacdysfunction, eight of whom died of progressive cardiac failure. There was no significant difference in the incidence of cardiac dysfunction between the divided and single dose infusion groups. More girls than boys developed cardiac dysfunction and more girls died of progressive cardiac failure; this difference was not statistically significant. The median time to the development of cardiac failure was 2 months. CONCLUSIONS: The divided dose regimen did not alter the incidence of cardiotoxicity. Other schedules should therefore be investigated. Our data suggest that, at similar cumulative doses, girls are more likely to develop cardiac dysfunction than are boys. If the sex-related difference is proved in larger series of patients, it may be prudent to lower the recommended cumulative doses for girls.

Efficacy of growth hormone replacement therapy in children with organic growth hormone deficiency after cranial irradiation.

We evaluated the growth response of 20 childhood cancer survivors who received growth hormone (GH) replacement therapy (0.3 mg/kg/week) for at least 12 months. In all subjects, GH deficiency was associated with cranial irradiation and was documented with growth charts, bone age, and somatomedin C levels; at least one GH stimulation test was available for 14 children. Pretreatment overall growth velocity was 3.3 +/- 0.5 cm/year (mean +/- SE) over a 3-year period. After GH replacement, growth velocity was 8.6 +/- 0.6 cm/year during the first year (n = 20), 7.2 +/- 0.5 cm/year during the second year (n = 17), 5.9 +/- 0.6 cm/year during the third year (n = 11), and (6.1 +/- 0.6 cm/year during the fourth year (n = 7). Growth response, tabulated by age at onset of GH replacement, was compared with the response in GH-naive children with idiopathic GH deficiency (data obtained through the Genentech Inc. National Cooperative Growth Study Summary, September 1991); the growth velocity fell within the range described for idiopathic GH deficiency adjusted for either chronological or bone age. We conclude that children with GH deficiency after cranial irradiation for neoplastic diseases respond to GH replacement therapy as well as children with idiopathic GH deficiency.