Phase I study of recombinant human interleukin-2 for pediatric malignancies: feasibility of outpatient therapy. A Pediatric Oncology Group Study.
Published data indicate that when recombinant interleukin-2 (rIL-2) is administered to children as a 15-min i.v. bolus, doses of 18 x 10(6) IU/m2 are poorly tolerated, requiring intensive care unit (ICU) management of IL-2-induced hypotension. We administered rIL-2 as a 1- or 2-h i.v. infusion to 11 children with malignancies refractory to conventional therapy. IL-2 was given every Monday/Wednesday/Friday for 3 weeks. Four children received 12 x 10(6) IU/m2/dose, four received 18 x 10(6) IU/m2/dose, and three received 24 x 10(6) IU/m2/dose (1 Cetus Unit = 6 IU). Fever, chills, flushing, nausea, vomiting, transient weight gain, and oliguria were observed at all three dose levels (not dose-limiting toxicities). Cardiovascular toxicity was significantly reduced compared to the bolus regimen. Mild hypotension was observed at all three dose levels; however, there was no severe dose-limiting hypotension. Because of reduced cardiovascular toxicity, IL-2 was safely administered on an outpatient basis. This regimen induced marginal transient increases in natural killer cell activity and lymphokine-activated killer cell activity. No measurable clinical tumor response was observed in any of the 11 children. The maximum-tolerated dose has not been reached. This regimen allows for a considerable cost reduction (outpatient care instead of ICU care) and safety, making further clinical trials on the use of IL-2 in children more feasible.
Pais
R C
RC
Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia.
Abdel-Mageed
A
A
Ghim
T T
TT
Ode
D
D
Melendez
E
E
Kim
H S
HS
Findley
H
H
Ragab
A H
AH
D000293:Adolescent; D000328:Adult; D000553:Ambulatory Care; D002319:Cardiovascular System / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D004064:Digestive System / Q000187:drug effects; D004487:Edema / Q000139:chemically induced; D006801:Humans; D007167:Immunotherapy; D007239:Infections / Q000209:etiology; D007262:Infusions, Intravenous; D007376:Interleukin-2 / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*
D007376:Interleukin-2