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Blood, 1 April 2007, Vol. 109, No. 7, pp. 2744-2750. Prepublished online as a Blood First Edition Paper on November 28, 2006; DOI 10.1182/blood-2006-07-035006. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-07-035006v1 109/7/2744    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Douer, D. Articles by Avramis, V. I. Search for Related Content PubMed PubMed Citation Articles by Douer, D. Articles by Avramis, V. I. Related Collections Neoplasia Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL TRIALS AND OBSERVATIONS Pharmacodynamics and safety of intravenous pegaspargase during remission induction in adults aged 55 years or younger with newly diagnosed acute lymphoblastic leukemia Dan Douer1, Henry Yampolsky1, Lewis J. Cohen1, Kristy Watkins1, Alexandra M. Levine1, Antonia P. Periclou2, and Vassilios I. Avramis1 1 Division of Hematology, Department of Medicine, and 2 Department of Pediatrics, Division of Hematology/Oncology, Childrens Hospital Los Angeles, University of Southern California Keck Medical School and Norris Comprehensive Cancer Center, Los Angeles In contrast to that in children, pharmacokinetic, pharmacodynamic, and safety information on pegaspargase in adults is very limited. We administered a single intravenous dose of pegaspargase (2000 IU/m2) as part of a standard frontline induction regimen to 25 adults with newly diagnosed acute lymphoblastic leukemia (ALL), and obtained serum samples on several time points. The population mean peak serum concentration of asparaginase enzymatic activity was 1 IU/mL, the elimination half-life was 7 days, and the volume of distribution was 2.43 L/m2. After the single dose, asparagine deamination was complete in all patients after 2 hours, and in 100%, 81%, and 44% on days 14, 21, and 28, respectively. A pharmocodynamic correlation model showed minimal enzymatic activity of 0.2 IU/mL for optimal asparagine depletion. The kinetic posthoc analyses demonstrated enzymatic activity for 3 weeks or more. One patient developed neutralizing antiasparaginase antibodies on day 22 after administration. Pegaspargase was well tolerated, with few grade 3/4 side effects. No allergic reactions or pancreatitis were observed. In adults aged 55 years or younger, pegaspargase produces a long duration of asparagine depletion and can be given intravenously, with a safety profile that is similar to equivalent multiple doses of intramuscular Escherichia coli asparaginase. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. H. Goldstone, S. M. Richards, H. M. Lazarus, M. S. Tallman, G. Buck, A. K. Fielding, A. K. Burnett, R. Chopra, P. H. Wiernik, L. Foroni, et al. In adults with standard-risk acute lymphoblastic leukemia, the greatest benefit is achieved from a matched sibling allogeneic transplantation in first complete remission, and an autologous transplantation is less effective than conventional consolidation/maintenance chemotherapy in all patients: final results of the International ALL Trial (MRC UKALL XII/ECOG E2993) Blood, February 15, 2008; 111(4): 1827 - 1833. [Abstract] [Full Text] [PDF] J. M. Rowe and A. H. Goldstone How I treat acute lymphocytic leukemia in adults Blood, October 1, 2007; 110(7): 2268 - 2275. [Abstract] [Full Text] [PDF]

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