Weight-based strategy of dose administration in children using intravenous busulfan: Clinical and pharmacokinetic results

• Published in: Pediatric blood & cancer Vol. 58; no. 1; pp. 90 - 97
• Main Authors: Michel, Gérard, Valteau-Couanet, Dominique, Gentet, Jean-Claude, Esperou, Hélène, Socié, Gérard, Méchinaud, Françoise, Doz, François, Neven, Bénédicte, Bertrand, Yves, Galambrun, Claire, Demeocq, François, Yakouben, Karima, Bordigoni, Pierre, Frappaz, Didier, Nguyen, Laurent, Vassal, Gilles
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.01.2012
• Subjects: Adolescent; Antineoplastic Agents, Alkylating - administration & dosage; Antineoplastic Agents, Alkylating - pharmacokinetics; Area Under Curve; Body Weight; Busulfan - administration & dosage; Busulfan - pharmacokinetics; Child; Child, Preschool; children; Combined Modality Therapy; Female; Follow-Up Studies; Hematologic Neoplasms - therapy; Hematopoietic Stem Cell Transplantation; Hepatic Veno-Occlusive Disease - prevention & control; Humans; Infant; Injections, Intravenous; intravenous busulfan; Male; pediatrics; pharmacokinetics; Prognosis; Survival Rate; Tissue Distribution; Transplantation, Homologous
• ISSN: 1545-5009; 1545-5017
• DOI: 10.1002/pbc.22959

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. Pediatr Blood Cancer 2012; 58: 90–97. © 2011 Wiley Periodicals, Inc.