Abstract |
A phase I trial of a murine anti- ganglioside (GD2) monoclonal antibody (mAb) 14G2a was conducted in 14 neuroblastoma patients and 1 osteosarcoma patient to assess its safety, toxicity and pharmacokinetics in pediatric patients. The pharmacokinetics of mAb 14G2a were biphasic with a t alpha 1/2 of 2.8 +/- 2.8 h and a t beta 1/2 of 18.3 +/- 11.8 h. In general, t beta 1/2 was dose-dependent with a level of significance of P = 0.036, and it reached a plateau at doses of 250 mg/m2 or more. Overall the peak serum levels were dose-dependent at P < 0.001. However, they demonstrated an abrupt increase between doses of 100 mg/m2 and 250 mg/m2. The latter two suggest a saturable mechanism for mAb elimination. In addition, peak serum concentrations were observed earlier at higher mAb doses, which indicates the achievement of a steady state. The t beta 1/2 of mAb 14G2a in children appears to be shorter than in adults. Furthermore, 2 patients demonstrated a considerable decrease in t beta 1/2 following retreatment with 14G2a. This was paralleled by high human anti-(mouse Ig) antibody levels. This study represents the first comprehensive analysis of murine mAb pharmacokinetics in children and will be useful in the future design of mAb therapy.
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Authors | M M Uttenreuther-Fischer, C S Huang, R A Reisfeld, A L Yu |
Journal | Cancer immunology, immunotherapy : CII
(Cancer Immunol Immunother)
Vol. 41
Issue 1
Pg. 29-36
(Jul 1995)
ISSN: 0340-7004 [Print] Germany |
PMID | 7641217
(Publication Type: Clinical Trial, Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Antibodies, Monoclonal
- Gangliosides
- ganglioside, GD2
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Topics |
- Adolescent
- Age Factors
- Antibodies, Monoclonal
(pharmacokinetics)
- Child
- Dose-Response Relationship, Immunologic
- Female
- Gangliosides
(immunology)
- Humans
- Male
- Metabolic Clearance Rate
- Neuroblastoma
(therapy)
- Osteosarcoma
(therapy)
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