Pharmacokinetics of high-dose etoposide administered in combination with fractionated total-body irradiation as conditioning for allogeneic hematopoietic stem cell transplantation in children with acute lymphoblastic leukemia

Pediatr Transplant. 2011 Feb;15(1):96-102. doi: 10.1111/j.1399-3046.2010.01418.x. Epub 2010 Dec 15.

Abstract

Etoposide (VP-16) is one of the most widely used antitumor agents in pediatric oncology as well as chemotherapeutic agents used in conditioning regimen prior to allo-HSCT for childhood ALL. This study included 21 children with ALL who underwent allo-HSCT after conditioning with FTBI and high-dose of VP-16 (60 mg/kg) given intravenously as single four-h infusion on day -3 (n=2) or day -4 (n=19) prior to allo-HSCT. Blood samples were collected at defined time intervals until 120 h elapsed from the end of infusion. VP-16 plasma concentrations were determined using validated HPLC method. Three-compartment model was assumed for assessing PK parameters of VP-16. The median value of VP-16 C(max) measured at the end of infusion was 188.0 μg/mL (range 148.0-407.0 μg/mL). Out of 21 studied children, VP-16 was still detectable in 17 patients 72 h (median concentration 0.31 μg/mL) and in eight patients 96 h (median concentration 0.31 μg/mL) after the end of infusion. VP-16 concentration 96 h after the end of infusion was positively correlated with VP-16 AUC and negatively correlated with VP-16 CL normalized to body weight.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antineoplastic Agents / pharmacokinetics*
  • Area Under Curve
  • Child
  • Child, Preschool
  • Chromatography, High Pressure Liquid / methods
  • Combined Modality Therapy / methods*
  • Etoposide / pharmacokinetics*
  • Female
  • Hematopoietic Stem Cell Transplantation / methods*
  • Humans
  • Male
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy*
  • Time Factors
  • Transplantation Conditioning / methods*
  • Transplantation, Homologous / methods*
  • Whole-Body Irradiation

Substances

  • Antineoplastic Agents
  • Etoposide