Pharmacokinetics of doxorubicin in children with acute lymphoblastic leukemia: Multi-institutional collaborative study
Frost, BM ; Eksborg, S ; Bjork, O ; Abrahamsson, J ; Behrendtz, M ; Castor, Anders LU
; Forestier, E
and Lonnerholm, G
(2002)
In Medical and Pediatric Oncology
38(5).
p.329-337
- Abstract
- Background, In adults, it has been shown that the pharmacokinetics of doxorubicin are highly variable, despite standardization of the dose based on body surface area (BSA). The purpose of this study was to determine the plasma concentrations of doxorubicin and its active metabolite doxorubicinol in children treated for acute lymphoblastic leukemia (ALL). Procedure. Children, 107 in number, aged 1.3-17.3 years, were studied at Day 1 of induction therapy according to the current Nordic protocol. Five infants, 3-9 months old, were also included. Plasma samples were drawn 23 hr after the start of a 24-hr infusion of doxorubicin 40 mg/m(2), and analyzed by reversed-phase liquid chromatography. Results. There was a more than 10-fold difference... (More)
- Background, In adults, it has been shown that the pharmacokinetics of doxorubicin are highly variable, despite standardization of the dose based on body surface area (BSA). The purpose of this study was to determine the plasma concentrations of doxorubicin and its active metabolite doxorubicinol in children treated for acute lymphoblastic leukemia (ALL). Procedure. Children, 107 in number, aged 1.3-17.3 years, were studied at Day 1 of induction therapy according to the current Nordic protocol. Five infants, 3-9 months old, were also included. Plasma samples were drawn 23 hr after the start of a 24-hr infusion of doxorubicin 40 mg/m(2), and analyzed by reversed-phase liquid chromatography. Results. There was a more than 10-fold difference between patients in dose normalized plasma concentration of doxorubicin, median 62.8 ng/ml, range 22.6-334 ng/ml. The doxorubicin concentrations differed significantly between age groups (P=0.003). Children aged 4-6 years had the highest doxorubicin concentrations, median 77.9 ng/ml, followed by 2-4-year-old children, median 64.3 ng/ml. Both younger and older children had median values of about 50 ng/ml. Patients with white blood cell (WBC) count > 50 x 10(9)/L at diagnosis had significantly lower doxorubicin concentrations, median 55.3 ng/ml, than those with WBC count < 10 x 10(9)/L, median 64.4 ng/ml (P 0,015). There was no difference in doxorubicin concentration between boys and girls. No correlation was found between doxorubicin levels and serum aminotransferases or serum creatinine. The concentration of doxorubicinol was 13% (median value) of that of doxorubicin. Four infants, 7-9 months old, had plasma clearance between 350-431 ml/min/m(2), which is in the same range as in older children. A 3-month-old infant had a clearance of 181 ml/min/m(2). Conclusions. The age groups who had the highest doxorubicin concentrations, (2-) 4-6-year-old children, are known to make up a large proportion of standard risk ALL cases with good prognosis. The correlation between doxorubicin plasma levels and clinical effect needs further study. The influence of age, body composition, and tumor burden on the pharmacokinetics of antineoplastic drugs should also be further explored, aiming at improvements in the current dosing regimen based on BSA. (C) 2002 Wiley-Liss, Inc. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/337844
- author
- Frost, BM
; Eksborg, S
; Bjork, O
; Abrahamsson, J
; Behrendtz, M
; Castor, Anders
LU
; Forestier, E
and Lonnerholm, G
- organization
- publishing date
- 2002
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- childhood cancer, pharmacokinetics, doxorubicin, anthracycline, acute, lymphoblastic leukemia
- in
- Medical and Pediatric Oncology
- volume
- 38
- issue
- 5
- pages
- 329 - 337
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- wos:000175446300006
- pmid:11979457
- scopus:0036246238
- ISSN
- 1096-911X
- DOI
- 10.1002/mpo.10052
- language
- English
- LU publication?
- yes
- id
- 292c523d-c402-4347-adb0-bab2fec34155 (old id 337844)
- date added to LUP
- 2016-04-01 12:00:13
- date last changed
- 2024-05-07 01:14:18
@article{292c523d-c402-4347-adb0-bab2fec34155,
abstract = {{Background, In adults, it has been shown that the pharmacokinetics of doxorubicin are highly variable, despite standardization of the dose based on body surface area (BSA). The purpose of this study was to determine the plasma concentrations of doxorubicin and its active metabolite doxorubicinol in children treated for acute lymphoblastic leukemia (ALL). Procedure. Children, 107 in number, aged 1.3-17.3 years, were studied at Day 1 of induction therapy according to the current Nordic protocol. Five infants, 3-9 months old, were also included. Plasma samples were drawn 23 hr after the start of a 24-hr infusion of doxorubicin 40 mg/m(2), and analyzed by reversed-phase liquid chromatography. Results. There was a more than 10-fold difference between patients in dose normalized plasma concentration of doxorubicin, median 62.8 ng/ml, range 22.6-334 ng/ml. The doxorubicin concentrations differed significantly between age groups (P=0.003). Children aged 4-6 years had the highest doxorubicin concentrations, median 77.9 ng/ml, followed by 2-4-year-old children, median 64.3 ng/ml. Both younger and older children had median values of about 50 ng/ml. Patients with white blood cell (WBC) count > 50 x 10(9)/L at diagnosis had significantly lower doxorubicin concentrations, median 55.3 ng/ml, than those with WBC count < 10 x 10(9)/L, median 64.4 ng/ml (P 0,015). There was no difference in doxorubicin concentration between boys and girls. No correlation was found between doxorubicin levels and serum aminotransferases or serum creatinine. The concentration of doxorubicinol was 13% (median value) of that of doxorubicin. Four infants, 7-9 months old, had plasma clearance between 350-431 ml/min/m(2), which is in the same range as in older children. A 3-month-old infant had a clearance of 181 ml/min/m(2). Conclusions. The age groups who had the highest doxorubicin concentrations, (2-) 4-6-year-old children, are known to make up a large proportion of standard risk ALL cases with good prognosis. The correlation between doxorubicin plasma levels and clinical effect needs further study. The influence of age, body composition, and tumor burden on the pharmacokinetics of antineoplastic drugs should also be further explored, aiming at improvements in the current dosing regimen based on BSA. (C) 2002 Wiley-Liss, Inc.}},
author = {{Frost, BM and Eksborg, S and Bjork, O and Abrahamsson, J and Behrendtz, M and Castor, Anders and Forestier, E and Lonnerholm, G}},
issn = {{1096-911X}},
keywords = {{childhood cancer; pharmacokinetics; doxorubicin; anthracycline; acute; lymphoblastic leukemia}},
language = {{eng}},
number = {{5}},
pages = {{329--337}},
publisher = {{John Wiley & Sons Inc.}},
series = {{Medical and Pediatric Oncology}},
title = {{Pharmacokinetics of doxorubicin in children with acute lymphoblastic leukemia: Multi-institutional collaborative study}},
url = {{http://dx.doi.org/10.1002/mpo.10052}},
doi = {{10.1002/mpo.10052}},
volume = {{38}},
year = {{2002}},
}