title: Drug monitoring of PEG-asparaginase treatment in childhood acute lymphoblastic leukemia and non-Hodgkin's lymphoma.
abstract: 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/m2 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.
authors.affiliation: Department of Pediatric Hematology and Oncology, University Children's Hospital Muenster Albert-Schweitzer-Strasse 33, 48129 Münster, Germany.
authors.forename: J P
authors.initials: JP
authors.lastname: Vieira Pinheiro
authors.forename: C
authors.initials: C
authors.lastname: Lanversa
authors.forename: G
authors.initials: G
authors.lastname: Würthwein
authors.forename: R
authors.initials: R
authors.lastname: Beier
authors.forename: J
authors.initials: J
authors.lastname: Casimiro da Palma
authors.forename: A
authors.initials: A
authors.lastname: von Stackelberg
authors.forename: J
authors.initials: J
authors.lastname: Boos
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001215:Asparaginase / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004342:Drug Hypersensitivity; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D007223:Infant; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy*; D008297:Male; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000493:pharmacokinetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D015203:Reproducibility of Results; D012189:Retrospective Studies
chemical_list: D011092:Polyethylene Glycols; C042705:pegaspargase; D001215:Asparaginase