Asparaginase pharmacokinetics after intensive polyethylene glycol-conjugated L-asparaginase therapy for children with relapsed acute lymphoblastic leukemia.
Clin Cancer Res
; 10(16): 5335-41, 2004 Aug 15.
Article
em En
| MEDLINE
| ID: mdl-15328169
ABSTRACT
PURPOSE:
Asparaginase therapy is an important component in the treatment of children with acute lymphoblastic leukemia. Polyethylene glycol-conjugated asparaginase (PEG-ASNase) has significant pharmacological advantages over native Escherichia coli asparaginase. We investigated the pharmacokinetics of PEG-ASNase, presence of antibodies to PEG-ASNase, and concentrations of asparagine in serum and cerebrospinal fluid (CSF) in combination chemotherapy for relapsed pediatric acute lymphoblastic leukemia. EXPERIMENTALDESIGN:
Twenty-eight pediatric patients with relapsed medullary (n = 16) and extramedullary (n = 11) acute lymphoblastic leukemia were enrolled at three pediatric institutions and had at least two serum and CSF samples obtained for analysis. Patients received induction therapy (including PEG-ASNase 2500 IU/m2 intramuscularly weekly on days 2, 9, 16, and 23) and intensification therapy (including PEG-ASNase 2500 IU/m2 intramuscularly once on day 7). Serum samples were obtained weekly during induction and intensification. CSF samples were obtained during therapeutic lumbar punctures during induction and intensification.RESULTS:
Weekly PEG-ASNase therapy resulted in PEG-ASNase activity of >0.1 IU/ml in 91-100% of patients throughout induction. During intensification, PEG-ASNase on day 7 resulted in PEG-ASNase activity >0.1 IU/ml in 94% and 80% of patients on days 14 and 21, respectively. Serum and CSF asparagine depletion was observed and maintained during induction and intensification in the majority of samples. PEG-ASNase antibody was observed in only 3 patients.CONCLUSIONS:
Intensive PEG-ASNase therapy in the treatment of relapsed acute lymphoblastic leukemia reliably results in high-level serum PEG-ASNase activity, and asparagine depletion in serum and CSF is usually achieved. Incorporation of intensive PEG-ASNase in future trials for recurrent acute lymphoblastic leukemia is warranted.
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Base de dados:
MEDLINE
Assunto principal:
Polietilenoglicóis
/
Asparaginase
/
Protocolos de Quimioterapia Combinada Antineoplásica
/
Leucemia-Linfoma Linfoblástico de Células Precursoras
Tipo de estudo:
Clinical_trials
Limite:
Adolescent
/
Child
/
Child, preschool
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Clin Cancer Res
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2004
Tipo de documento:
Article
País de afiliação:
Estados Unidos