Pharmacokinetics of recombinant interleukin-2 in children with malignancies: a Pediatric Oncology Group study.
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.
Pais
R C
RC
Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322.
Ingrim
N B
NB
Garcia
M L
ML
Abdel-Mageed
A
A
McKolanis
J
J
Ingrim
M E
ME
Hnath
R S
RS
Ziegler
K
K
Ragab
A H
AH
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*
D007376:Interleukin-2; D011994:Recombinant Proteins