Pharmacokinetics, pharmacodynamics, efficacy, and safety of a new recombinant asparaginase preparation in children with previously untreated acute lymphoblastic leukemia: a randomized phase 2 clinical trial
- 15 December 2008
- journal article
- research article
- Published by American Society of Hematology in Blood
- Vol. 112 (13), 4832-4838
- https://doi.org/10.1182/blood-2008-04-149443
Abstract
The pharmacokinetics, pharmacodynamics, efficacy, and safety of a new recom-binant Escherichia coli–asparaginase preparation was compared with Asparaginase medac. Thirty-two children with acute lymphoblastic leukemia were randomized to receive one of both agents at a dose of 5000 U/m2 every 3 days, for a total of 8 doses during induction treatment. The serum activity-time profile after the first dose of recombinant asparaginase was similar to that of Asparaginase medac. The trough serum activities were greater than the desired threshold of 100 U/L in both treatment groups. Asparagine was completely depleted in serum and in cerebrospinal fluid, whereas glutamine levels were only moderately influenced. No significant difference between the 2 treatments regarding the degree of asparagine depletion, duration of depletion, complete remission rate, and minimal residual disease status at the end of induction, overall frequency or intensity of adverse events was seen. Observed adverse reactions are known as possible and labeled side effects of asparaginase treatment and chemotherapy. We conclude that the new recombinant asparaginase and other native Asparaginase medac are bioequivalent and have the same pharmacodynamic effects and the same direct toxicity profile in children with acute lymphoblastic leukemia. This trial was registered at http://www.controlled-trials.com as no. ISRCTN 75734403.Keywords
This publication has 11 references indexed in Scilit:
- Results of the Dana-Farber Cancer Institute ALL Consortium Protocol 95-01 for children with acute lymphoblastic leukemiaBlood, 2006
- Minimal residual disease (MRD) measurement as a tool to compare the efficacy of chemotherapeutic drug regimens using Escherichia Coli‐asparaginase or Erwinia‐asparaginase in childhood acute lymphoblastic leukemia (ALL)Pediatric Blood & Cancer, 2005
- Pharmacokinetic/Pharmacodynamic Relationships of Asparaginase FormulationsClinical Pharmacokinetics, 2005
- The best way to use asparaginase in childhood acute lymphatic leukaemia – still to be defined?British Journal of Haematology, 2004
- Analytical validation of a microplate reader-based method for the therapeutic drug monitoring of l-asparaginase in human serumAnalytical Biochemistry, 2002
- Comparison of Escherichia coli-asparaginase with Erwinia-asparaginase in the treatment of childhood lymphoid malignancies: results of a randomized European Organisation for Research and Treatment of Cancer---Children's Leukemia Group phase 3 trialBlood, 2002
- Effect of Protracted High-Dose l-Asparaginase Given as a Second Exposure in a Berlin-Frankfurt-Münster–Based Treatment: Results of the Randomized 9102 Intermediate-Risk Childhood Acute Lymphoblastic Leukemia Study—A Report From the Associazione Italiana Ematologia Oncologia PediatricaJournal of Clinical Oncology, 2001
- Improved outcome for children with acute lymphoblastic leukemia: results of Dana-Farber Consortium Protocol 91-01Blood, 2001
- Monitoring of asparaginase activity and asparagine levels in children on different asparaginase preparationsEuropean Journal of Cancer, 1996
- Comparative pharmacokinetic studies of three asparaginase preparations.Journal of Clinical Oncology, 1993