Etoposide pharmacokinetics in children treated for acute myeloid leukemia

Anticancer Drugs. 2006 Oct;17(9):1087-94. doi: 10.1097/01.cad.0000231470.54288.49.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Alanine Transaminase / blood
  • Antineoplastic Agents, Phytogenic / pharmacokinetics*
  • Child
  • Child, Preschool
  • Down Syndrome / metabolism
  • Etoposide / pharmacokinetics*
  • Female
  • Humans
  • Infant
  • Male
  • Metabolic Clearance Rate
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*

Substances

  • Antineoplastic Agents, Phytogenic
  • Etoposide
  • Alanine Transaminase