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Once-daily intravenous busulfan in children prior to stem cell transplantation: study of pharmacokinetics and early clinical outcomes.
Anticancer Drugs. 2006 Oct; 17(9):1099-105.AD

Abstract

We studied the pharmacokinetics and clinical outcome of a new once-daily intravenous area under the curve-targeted dosing scheme for busulfan based on body surface area. Eighteen children undergoing busulfan-based conditioning for allogeneic stem cell transplantation were enrolled. The age of the children ranged from 0.5 to 16 years. For all children, the starting dose was 80 mg/m. Unlimited dose adjustment was allowed to reach the target area under the curve (3800 micromol/l . min). This target area under the curve was determined on the basis of a previous study in our hospital. Pharmacokinetic studies were performed after the first dose. The median area under the curve on day 1 was 2616 (range 1781-5040) micromol/l . min at a dose of 80 mg/m. This resulted in a median dose increment to 114 (range 62-168) mg/m to reach the target area under the curve. In only one patient, the dose was decreased. Donor engraftment was established in 14 out of 18 patients (78%). Two of the four patients were successfully retransplanted. Relapse occurred in two patients (one died, one received additional treatment). Fourteen patients survived with a median follow-up of 1.6 years (1.0-2.2 years). The disease-free survival was 66% (12 of 18 patients). Despite the high systemic peak levels, there was no new unexpected or unusual toxicity. Moderate veno-occlusive disease was seen in one patient only. We conclude that intravenous busulfan in children administered once daily is safe, convenient and feasible, and can be dosed surface-based, independent of age. There was very limited (liver) toxicity, but the rejection rate was relative high, which can be probably overcome by a higher exposure to busulfan. Future investigations should be aimed at further optimizing the target area under the curve of intravenous busulfan for specific patient groups.

Authors+Show Affiliations

Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, The Netherlands. J.Zwaveling@lumc.nlNo 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

17001185

Citation

Zwaveling, Juliette, et al. "Once-daily Intravenous Busulfan in Children Prior to Stem Cell Transplantation: Study of Pharmacokinetics and Early Clinical Outcomes." Anti-cancer Drugs, vol. 17, no. 9, 2006, pp. 1099-105.
Zwaveling J, den Hartigh J, Lankester AC, et al. Once-daily intravenous busulfan in children prior to stem cell transplantation: study of pharmacokinetics and early clinical outcomes. Anticancer Drugs. 2006;17(9):1099-105.
Zwaveling, J., den Hartigh, J., Lankester, A. C., Guchelaar, H. J., Egeler, R. M., Bredius, R. G., & Maarten Bredius, R. G. (2006). Once-daily intravenous busulfan in children prior to stem cell transplantation: study of pharmacokinetics and early clinical outcomes. Anti-cancer Drugs, 17(9), 1099-105.
Zwaveling J, et al. Once-daily Intravenous Busulfan in Children Prior to Stem Cell Transplantation: Study of Pharmacokinetics and Early Clinical Outcomes. Anticancer Drugs. 2006;17(9):1099-105. PubMed PMID: 17001185.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Once-daily intravenous busulfan in children prior to stem cell transplantation: study of pharmacokinetics and early clinical outcomes. AU - Zwaveling,Juliette, AU - den Hartigh,Jan, AU - Lankester,Arjan C, AU - Guchelaar,Henk-Jan, AU - Egeler,R Maarten, AU - Bredius,Robbert G, AU - Maarten Bredius,Robbert G, PY - 2006/9/27/pubmed PY - 2006/12/9/medline PY - 2006/9/27/entrez SP - 1099 EP - 105 JF - Anti-cancer drugs JO - Anticancer Drugs VL - 17 IS - 9 N2 - We studied the pharmacokinetics and clinical outcome of a new once-daily intravenous area under the curve-targeted dosing scheme for busulfan based on body surface area. Eighteen children undergoing busulfan-based conditioning for allogeneic stem cell transplantation were enrolled. The age of the children ranged from 0.5 to 16 years. For all children, the starting dose was 80 mg/m. Unlimited dose adjustment was allowed to reach the target area under the curve (3800 micromol/l . min). This target area under the curve was determined on the basis of a previous study in our hospital. Pharmacokinetic studies were performed after the first dose. The median area under the curve on day 1 was 2616 (range 1781-5040) micromol/l . min at a dose of 80 mg/m. This resulted in a median dose increment to 114 (range 62-168) mg/m to reach the target area under the curve. In only one patient, the dose was decreased. Donor engraftment was established in 14 out of 18 patients (78%). Two of the four patients were successfully retransplanted. Relapse occurred in two patients (one died, one received additional treatment). Fourteen patients survived with a median follow-up of 1.6 years (1.0-2.2 years). The disease-free survival was 66% (12 of 18 patients). Despite the high systemic peak levels, there was no new unexpected or unusual toxicity. Moderate veno-occlusive disease was seen in one patient only. We conclude that intravenous busulfan in children administered once daily is safe, convenient and feasible, and can be dosed surface-based, independent of age. There was very limited (liver) toxicity, but the rejection rate was relative high, which can be probably overcome by a higher exposure to busulfan. Future investigations should be aimed at further optimizing the target area under the curve of intravenous busulfan for specific patient groups. SN - 0959-4973 UR - https://www.unboundmedicine.com/medline/citation/17001185/Once_daily_intravenous_busulfan_in_children_prior_to_stem_cell_transplantation:_study_of_pharmacokinetics_and_early_clinical_outcomes_ L2 - https://doi.org/10.1097/01.cad.0000231482.15277.48 DB - PRIME DP - Unbound Medicine ER -