Dose reduction of asparaginase under pharmacokinetic and pharmacodynamic control during induction therapy in children with acute lymphoblastic leukaemia

The enzyme asparaginase is an important element in the therapy of acute lymphoblastic leukaemia (ALL). The usual asparaginase dose as prescribed in the ALL‐BFM‐86/90 treatment protocol for the therapy of ALL is 10 000 IU/m2 at 3 d intervals and had been developed on the basis of the E. coli asparagi...

Full description

Saved in:
Bibliographic Details
Published in:British journal of haematology 1997-03, Vol.96 (4), p.675-681
Main Authors: AHLKE, ELVIRA, NOWAK‐GO¨TTL, ULRIKE, SCHULZE‐WESTHOFF, PETRA, WERBER, GISELA, BO¨RSTE, HEDWIG, WU¨RTHWEIN, GUDRUN, JU¨RGENS, HERBERT, BOOS, JOACHIM
Format: Article
Language:English
Subjects:
Adolescent
Amino Acids - metabolism
Antineoplastic agents
Antineoplastic Agents - administration & dosage
Antineoplastic Agents - pharmacokinetics
asparaginase
Asparaginase - administration & dosage
Asparaginase - pharmacokinetics
Biological and medical sciences
Blood Coagulation
Chemotherapy
Child
Child, Preschool
childhood leukaemia
Clinical Protocols
coagulation parameters
dose reduction
Dose-Response Relationship, Drug
Humans
Infant
Medical sciences
pharmacokinetics
Pharmacology. Drug treatments
Precursor Cell Lymphoblastic Leukemia-Lymphoma - blood
Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy
Precursor Cell Lymphoblastic Leukemia-Lymphoma - metabolism
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The enzyme asparaginase is an important element in the therapy of acute lymphoblastic leukaemia (ALL). The usual asparaginase dose as prescribed in the ALL‐BFM‐86/90 treatment protocol for the therapy of ALL is 10 000 IU/m2 at 3 d intervals and had been developed on the basis of the E. coli asparaginase preparation CrasnitinTM from the Bayer company. Using the described schedule the E. coli asparaginase preparation from the Medac company shows significantly higher biological activity than the Bayer preparation. These findings prompted an attempt to reduce the dose of the Asparaginase medacTM under careful pharmacokinetic and pharmacodynamic monitoring. At the first step of dose reduction in ALL treatment protocol I, 11 children received 5000 IU/m2 of Asparaginase medacTM. Another 15 children were given 2500 IU/m2 of the enzyme at the second step of dose reduction. Prior to each asparaginase dose, blood samples were taken to determine amino acids and trough enzyme activity. Concurrent with the asparaginase monitoring, the coagulation parameters were measured. 96% of samples from the first step of dose reduction (5000 IU/m2 every third day) showed complete L‐asparagine depletion (
ISSN:0007-1048
1365-2141
DOI:10.1046/j.1365-2141.1997.d01-2089.x