Pharmacokinetic and pharmacodynamic properties of calaspargase pegol Escherichia coli L-asparaginase in the treatment of patients with acute lymphoblastic leukemia: results from Children's Oncology Group Study AALL07P4.
J Clin Oncol
; 32(34): 3874-82, 2014 Dec 01.
Article
em En
| MEDLINE
| ID: mdl-25348002
ABSTRACT
PURPOSE:
Asparaginase is a critical agent used to treat acute lymphoblastic leukemia (ALL). Pegaspargase (SS-PEG), a pegylated form of Escherichia coli L-asparaginase with a succinimidyl succinate (SS) linker, is the first-line asparaginase product used in Children's Oncology Group (COG) ALL trials. Calaspargase pegol (SC-PEG) replaces the SS linker in SS-PEG with a succinimidyl carbamate linker, creating a more stable molecule. COG AALL07P4 was designed to determine the pharmacokinetic and pharmacodynamic comparability of SC-PEG to SS-PEG in patients with newly diagnosed high-risk (HR) B-cell ALL. PATIENTS ANDMETHODS:
A total of 165 evaluable patients were randomly assigned at a 21 ratio to receive SC-PEG at 2,100 (SC-PEG2100; n = 69) or 2,500 IU/m(2) (SC-PEG2500; n = 42) versus SS-PEG 2,500 IU/m(2) (SS-PEG2500; n = 54) as part of an otherwise identical chemotherapy regimen. The groups were similar demographically, except more female patients received SC-PEG2500.RESULTS:
The mean half-life of plasma asparaginase activity for both SC-PEG doses was approximately 2.5× longer than that of SS-PEG2500. The total systemic exposure, as defined by induction area under the curve from time 0 to 25 days, was greater with SC-PEG2500 than with SS-PEG2500 or SC-PEG2100. The proportion of patients with plasma asparaginase activity ≥ 100 mIU/mL and ≥ 400 mIU/mL was higher in patients who received SC-PEG as compared with SS-PEG2500. After one dose of pegylated asparaginase on induction day 4, plasma asparagine was undetectable for 11 days for SS-PEG2500 and 18 days for both SC-PEG groups.CONCLUSION:
SC-PEG2500 achieves a significantly longer period of asparaginase activity above defined thresholds and asparagine depletion compared with SS-PEG2500 and has a comparable toxicity profile in children with HR B-cell ALL.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Polietilenoglicóis
/
Asparaginase
/
Protocolos de Quimioterapia Combinada Antineoplásica
/
Leucemia-Linfoma Linfoblástico de Células Precursoras
/
Antineoplásicos
Tipo de estudo:
Clinical_trials
/
Diagnostic_studies
/
Prognostic_studies
Limite:
Adolescent
/
Adult
/
Child
/
Child, preschool
/
Female
/
Humans
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Infant
/
Male
País/Região como assunto:
America do norte
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article