Weight-based strategy of dose administration in children using intravenous busulfan: clinical and pharmacokinetic results.
Pediatr Blood Cancer
; 58(1): 90-7, 2012 Jan.
Article
em En
| MEDLINE
| ID: mdl-21254374
ABSTRACT
BACKGROUND:
A prospective clinical trial was performed in order to validate the pharmacokinetic (PK) and clinical benefits of a new dosing schedule of intravenous busulfan (IV Bu) in children. PROCEDURE IV Bu was administered as a 2-hr infusion every 6 hr for 4 days. Five dose levels were given according to body-weight strata.RESULTS:
The 67 children aged from 4 months to 17.2 years were followed up over 50 months after autologous or allogeneic stem-cell transplantation. Reduced PK variability was seen after IV Bu administration enabling efficient targeting with 78% of patients within the 900-1,500 µM · min therapeutic window and reproducible exposures across administrations. No neurological complications occurred. The low incidence of hepatic veno-occlusive disease (VOD) recorded was not correlated with high area under the curve (AUC). Only stomatitis was correlated with high AUC in the autologous group. The 4-year overall survival was 59% in the autologous group and 82% in the allogeneic group.CONCLUSION:
The new dosing schedule using IV Bu provides adequate therapeutic targeting from the first administration, with low toxicity and good disease control in high-risk children. The choice of this formulation of Bu should be considered because of its low morbidity and good outcome.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Peso Corporal
/
Bussulfano
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Transplante de Células-Tronco Hematopoéticas
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Neoplasias Hematológicas
Tipo de estudo:
Clinical_trials
/
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Adolescent
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Child
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Child, preschool
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Female
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Humans
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Infant
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Male
Idioma:
En
Revista:
Pediatr Blood Cancer
Assunto da revista:
HEMATOLOGIA
/
NEOPLASIAS
/
PEDIATRIA
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
França