Etoposide pharmacokinetics in children treated for acute myeloid leukemia.
We studied the pharmacokinetics of etoposide in 45 children treated for newly diagnosed acute myeloid leukemia. Etoposide, 100 mg/m body surface area/24 h, was administered by 96-h continuous intravenous infusion. Concomitantly, the children received cytarabine 200 mg/m/24 h by intravenous infusion and 6-thioguanine 100 mg/m twice daily orally. Median total body clearance in children 0.5-1.8 (n=4) and 2.3-17.7 years old (n=36) without Down's syndrome was 17.1 and 17.6 ml/min/m, respectively (P=0.96). Five children with Down's syndrome had a median clearance of 13.6 ml/min/m (P=0.067 compared with non-Down's syndrome children). Eighteen of the children received a second identical treatment course 3-4 weeks later; there was a significant correlation between individual clearance values (rho=0.56; P=0.017). We found no significant correlation between etoposide pharmacokinetics and the remission rate or the relapse rate. In conclusion, our findings indicate that special dose-calculation guidelines for infants above 3 months old are not substantiated by age-dependent pharmacokinetics of etoposide. Down's syndrome children might be candidates for dose reduction if our data are confirmed in larger numbers of patients. Low course-to-course variability indicates that pharmacokinetically guided dosing of etoposide might be clinically relevant, if larger studies can demonstrate that this approach decreases toxicity or increases response rates.
Palle
Josefine
J
Department of Women's and Children's Health, University Children's Hospital, Uppsala, Sweden. josefine.palle@akademiska.se
Frost
Britt-Marie
BM
Britt-Marie
Frost
F
Gustafsson
Göran
G
Göran
Gustafsson
G
Hellebostad
Marit
M
Marit
Hellebostad
H
Kanerva
Jukka
J
Jukka
Kanerva
K
Liliemark
Eva
E
Eva
Liliemark
L
Schmiegelow
Kjeld
K
Kjeld
Schmiegelow
S
Lönnerholm
Gudmar
G
Gudmar
Lönnerholm
L
D000293:Adolescent; D000410:Alanine Transaminase / Q000097:blood; D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D004314:Down Syndrome / Q000378:metabolism; D005047:Etoposide / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008657:Metabolic Clearance Rate; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*
D000972:Antineoplastic Agents, Phytogenic; D005047:Etoposide; D000410:Alanine Transaminase