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Weight-based strategy of dose administration in children using intravenous busulfan: clinical and pharmacokinetic results.
Pediatr Blood Cancer. 2012 Jan; 58(1):90-7.PB

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.

Authors+Show Affiliations

Pediatric Hematology, Hopital Enfants Timone, Marseille, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

21254374

Citation

Michel, Gérard, et al. "Weight-based Strategy of Dose Administration in Children Using Intravenous Busulfan: Clinical and Pharmacokinetic Results." Pediatric Blood & Cancer, vol. 58, no. 1, 2012, pp. 90-7.
Michel G, Valteau-Couanet D, Gentet JC, et al. Weight-based strategy of dose administration in children using intravenous busulfan: clinical and pharmacokinetic results. Pediatr Blood Cancer. 2012;58(1):90-7.
Michel, G., Valteau-Couanet, D., Gentet, J. C., Esperou, H., Socié, G., Méchinaud, F., Doz, F., Neven, B., Bertrand, Y., Galambrun, C., Demeocq, F., Yakouben, K., Bordigoni, P., Frappaz, D., Nguyen, L., & Vassal, G. (2012). Weight-based strategy of dose administration in children using intravenous busulfan: clinical and pharmacokinetic results. Pediatric Blood & Cancer, 58(1), 90-7. https://doi.org/10.1002/pbc.22959
Michel G, et al. Weight-based Strategy of Dose Administration in Children Using Intravenous Busulfan: Clinical and Pharmacokinetic Results. Pediatr Blood Cancer. 2012;58(1):90-7. PubMed PMID: 21254374.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Weight-based strategy of dose administration in children using intravenous busulfan: clinical and pharmacokinetic results. AU - Michel,Gérard, AU - Valteau-Couanet,Dominique, AU - Gentet,Jean-Claude, AU - Esperou,Hélène, AU - Socié,Gérard, AU - Méchinaud,Françoise, AU - Doz,François, AU - Neven,Bénédicte, AU - Bertrand,Yves, AU - Galambrun,Claire, AU - Demeocq,François, AU - Yakouben,Karima, AU - Bordigoni,Pierre, AU - Frappaz,Didier, AU - Nguyen,Laurent, AU - Vassal,Gilles, Y1 - 2011/01/19/ PY - 2010/07/23/received PY - 2010/11/11/accepted PY - 2011/1/22/entrez PY - 2011/1/22/pubmed PY - 2012/1/13/medline SP - 90 EP - 7 JF - Pediatric blood & cancer JO - Pediatr Blood Cancer VL - 58 IS - 1 N2 - 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. SN - 1545-5017 UR - https://www.unboundmedicine.com/medline/citation/21254374/Weight_based_strategy_of_dose_administration_in_children_using_intravenous_busulfan:_clinical_and_pharmacokinetic_results_ L2 - https://doi.org/10.1002/pbc.22959 DB - PRIME DP - Unbound Medicine ER -