title: Pharmacokinetics of recombinant interleukin-2 in children with malignancies: a Pediatric Oncology Group study.
abstract: To develop effective interleukin-2 (IL-2) protocols for pediatric malignancies, it is important to define IL-2 pharmacokinetics in children. In a phase I trial, we studied IL-2 pharmacokinetics in seven children, aged 6-18, five with leukemia, one with neuroblastoma, and one with rhabdomyosarcoma. IL-2 was administered as a 15-min i.v. infusion of either 1 X 10(6) CU/m2/dose or 3 X 10(6) CU/m2/dose (every Monday, Wednesday, and Friday for 3 weeks). IL-2 levels were determined using an IL-2-dependent murine T lymphocyte cell line bioassay. Peak IL-2 levels of 120-426 and 330-740 CU/ml were achieved after the lower and higher doses, respectively. Pediatric IL-2 kinetics resembled data reported for adults, fitting a two-compartment model (least-squares-regression technique), with an alpha half-life of 14.0 +/- 5.6 min (range, 6.3-23.1) and a beta half-life of 51.4 +/- 10.7 min (range, 33.0-66.0). The volume of distribution approximated total extracellular fluid (mean, 0.18 L/kg). Further clinical trials are needed to identify which pediatric malignancies are sensitive to immunotherapy and to establish the optimal treatment regimens.
authors: Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322.
authors: R C
authors: RC
authors: Pais
authors: N B
authors: NB
authors: Ingrim
authors: M L
authors: ML
authors: Garcia
authors: A
authors: A
authors: Abdel-Mageed
authors: J
authors: J
authors: McKolanis
authors: M E
authors: ME
authors: Ingrim
authors: R S
authors: RS
authors: Hnath
authors: K
authors: K
authors: Ziegler
authors: A H
authors: AH
authors: Ragab
mesh_terms: D000293:Adolescent; D002648:Child; D004341:Drug Evaluation; D006801:Humans; D007376:Interleukin-2 / Q000493:pharmacokinetics* / Q000627:therapeutic use; D009447:Neuroblastoma / Q000188:drug therapy / Q000378:metabolism*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000378:metabolism*; D011994:Recombinant Proteins / Q000493:pharmacokinetics / Q000627:therapeutic use; D012208:Rhabdomyosarcoma / Q000188:drug therapy / Q000378:metabolism*
chemical_list: D007376:Interleukin-2; D011994:Recombinant Proteins