Pharmacokinetics of human-mouse chimeric anti-GD2 mAb ch14.18 in a phase I trial in neuroblastoma patients.
A comprehensive analysis of the pharmacokinetics of human-mouse chimeric anti-ganglioside GD2 antibody mAb ch14.18 was performed during a phase 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/m2 to 200 mg/m2. The plasma clearance of ch14.18 was biphasic. Following the first course of treatment t1/2,alpha was 3.4 +/- 3.1 h and t1/2,beta 66.6 +/- 27.4 h in 9/10 children. The t1/2,beta values were significantly less than those of 181 +/- 73 h previously reported in adult melanoma patients (P < or = 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, administered to 5/10 children, t1/2,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 different, and furthermore that repeated administration of mAb ch14.18 to children with neuroblastoma leads to accelerated antibody clearance.
Uttenreuther-Fischer
M M
MM
Charité Kinderklinik, Berlin, Germany.
Huang
C S
CS
Yu
A L
AL
D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000276:immunology / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000378:metabolism / Q000628:therapy; D002648:Child; D002675:Child, Preschool; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D005678:G(M2) Ganglioside / Q000276:immunology*; D006207:Half-Life; D006801:Humans; D007074:Immunoglobulin G / Q000235:genetics; D007145:Immunoglobulin kappa-Chains / Q000737:chemistry; D007167:Immunotherapy; D007223:Infant; D008297:Male; D051379:Mice; D009447:Neuroblastoma / Q000378:metabolism / Q000628:therapy*; D012516:Osteosarcoma / Q000378:metabolism / Q000628:therapy; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000493:pharmacokinetics* / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D007145:Immunoglobulin kappa-Chains; D011993:Recombinant Fusion Proteins; D005678:G(M2) Ganglioside