Mm. Uttenreutherfischer et al., PHARMACOKINETICS OF HUMAN-MOUSE CHIMERIC ANTI-GD2 MAB CH14.18 IN A PHASE-I TRIAL IN NEUROBLASTOMA PATIENTS, Cancer immunology and immunotherapy, 41(6), 1995, pp. 331-338
A comprehensive analysis of the pharmacokinetics of human-mouse chimer
ic anti-ganglioside GD2 antibody mAb ch14.18 was performed during a ph
ase I clinical trial of ten children with neuroblastoma and one adult
with osteosarcoma. The patients received a total of 20 courses of ch14
.18 at dose levels from 10 mg/m(2) to 200 mg/m(2). The plasma clearanc
e of ch14.18 was biphasic. Following the first course of treatment t(1
/2,alpha) was 3.4 +/- 3.1 h and t(1/2,beta) 66.6 +/- 27.4 h in 9/10 ch
ildren. The t(1/2,beta) values were significantly less than those of 1
81 +/- 73 h previously reported in adult melanoma patients (P less tha
n or equal to 0.001), and 147.5 h in the adult osteosarcoma patient in
our trial. The latter suggests different pharmacokinetics of mAb ch14
.18 in children and adults. After a second course of treatment, admini
stered to 5/10 children, t(1/2,beta) decreased significantly from 72.9
+/- 19.8 h to 31.7 +/- 18.4 h (P = 0.015). We therefore conclude that
the elimination kinetics of mAbs ch14.18 in children and adults are d
ifferent, and furthermore that repeated administration of mAb ch14.18
to children with neuroblastoma leads to accelerated antibody clearance
.