Drug Monitoring of PEG-Asparaginase Treatment in Childhood Acute Lymphoblastic Leukemia and Non-Hodgkin's Lymphoma

• Published in: Leukemia & lymphoma 2002-10, Vol.43 (10), p.1911-1920
• Main Authors: Pinheiro, J.P. Vieira, Lanvers, C., Würthwein, G., Beier, R., Casimiro da Palma, J., von Stackelberg, A., Boos, J.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; All; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Asparaginase; Asparaginase - administration & dosage; Asparaginase - blood; Asparaginase - pharmacokinetics; Child; Child, Preschool; Children; Dose-Response Relationship, Drug; Drug Hypersensitivity; Drug Monitoring; Female; Humans; Infant; Lymphoma, Non-Hodgkin - drug therapy; Male; Pharmacokinetics; Polyethylene Glycols - administration & dosage; Polyethylene Glycols - pharmacokinetics; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy; Reproducibility of Results; Retrospective Studies
• ISSN: 1042-8194; 1029-2403
• DOI: 10.1080/1042819021000015853

This is an updated review of the pharmacokinetic profile of PEG-asparaginase (PEG-ASNase) in childhood acute lymphoblastic leukemia (ALL) or non-Hodgkin's lymphoma (NHL). In a total of 271 children undergoing ALL/NHL or relapsed ALL treatment according to the Berlin-Frankfurt-Münster (BFM) protocols, drug monitoring of ASNase serum activity was performed after PEG-ASNase infusions. From December 1996 to July 2000, 1667 samples after 362 intravenous administrations of either 500, 750, 1000 or 2500 IU/m 2 PEG-ASNase were analyzed. Three weeks after infusion when relating the ASNase activity to the four-dose levels significant differences were not observed. Large interpatient variability was seen at each dose level resulting in a relevant number of patients not achieving adequate treatment intensity. Neither the extent of ASNase pre-treatment nor a prior event of a hypersensitivity reaction against unmodified ASNase had any impact on PEG-ASNase pharmacokinetics. It is concluded that escalation of the dose of PEG-ASNase did not result in a significant prolongation of time with activity values considered therapeutic. Depending on the desired endpoint, a second administration of PEG-ASNase seems to be more favorable than increasing the dose. For a safer recommendation, further investigations assessing the pharmacodynamic profile are required. Drug monitoring is advisable for early detection of patients with rapid elimination in order to ensure maximum treatment intensity.