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Pharmacokinetics of anti-ganglioside GD2 mAb 14G2a in a phase I trial in pediatric cancer patients.

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.
AuthorsM M Uttenreuther-Fischer, C S Huang, R A Reisfeld, A L Yu
JournalCancer immunology, immunotherapy : CII (Cancer Immunol Immunother) Vol. 41 Issue 1 Pg. 29-36 (Jul 1995) ISSN: 0340-7004 [Print] Germany
PMID7641217 (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.)
Chemical References
  • Antibodies, Monoclonal
  • Gangliosides
  • ganglioside, GD2
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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