Pharmacokinetics of anti-ganglioside GD2 mAB 14G2a in a phase I trial in pediatric cancer patients
Resource
CANCER IMMUNOLOGY, IMMUNOTHERAPY v.41 n.1 pp.29-36
Journal
CANCER IMMUNOLOGY, IMMUNOTHERAPY v.41 n.1 pp.29-36
Pages
-
Date Issued
1995
Date
1995
Author(s)
UTTRNREUTHER-FISCHER MARTINA M.
HUANG, CHIUN-SHENG
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 tα1/2 of 2.8 ±2.8 h and a tβ1/2 of 18.3±11. 8h. In general, tβ1/2 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/㎡ and 250 mg/㎡. 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 a tβ1/2 of mAb 14G2a in children appears to be shorter than in adults. Furthermore, 2 patients demonstrated a considerable decrease in a tβ1/2 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.#2183#
SDGs
Type
journal article