Pharmacokinetics-based integration of multiple doses of intravenous pegaspargase in a pediatric regimen for adults with newly diagnosed acute lymphoblastic leukemia Journal Article


Authors: Douer, D.; Aldoss, I.; Lunning, M. A.; Burke, P. W.; Ramezani, L.; Mark, L.; Vrona, J.; Park, J. H.; Tallman, M. S.; Avramis, V. I.; Pullarkat, V.; Mohrbacher, A. M.
Article Title: Pharmacokinetics-based integration of multiple doses of intravenous pegaspargase in a pediatric regimen for adults with newly diagnosed acute lymphoblastic leukemia
Abstract: Asparaginase treatment is standard in all pediatric acute lymphoblastic leukemia (ALL) regimens, whereas in adults, it is either excluded or administered for a shorter duration. Several adult ALL protocols are adapting pediatric regimens, but the optimal implementation of asparaginase is not well studied, considering its potential higher toxicity. We studied a pegaspargase dosing strategy based on its pharmacokinetic characteristics in adults. Between 2004 and 2009, 51 adults age 18 to 57 years with newly diagnosed ALL were treated with a regimen adapted from a pediatric trial that included six doses of intravenous pegaspargase at 2,000 IU/m(2) per dose. Intervals between doses were longer than 4 weeks and rationally synchronized with other chemotherapy drugs to prevent overlapping toxicities. Pegaspargase was administered with steroids to reduce hypersensitivity. Asparaginase-related toxicities were monitored after 173 pegaspargase doses. The most common grade 3/4 asparaginase-related toxicities were lengthy hyperbilirubinemia and transaminitis, occasionally resulting in subsequent treatment delays. All toxicities resolved spontaneously. Forty-five percent of patients were able to receive all six doses of pegaspargase, and 61% received ≥ three doses. In only 20% of patients, the drug was discontinued after pegaspargase-related serious toxicity. Ninety-six percent achieved complete remission, almost all within 4 weeks, and a low induction death rate was seen. Seven-year disease-free and overall survival were 58% and 51%, respectively. Our dose and schedule of pegaspargase, based on its pharmacokinetics, and our detailed toxicity profile could be applied for safer adaptation of pediatric ALL protocols in adults.
Keywords: adult; treatment outcome; disease-free survival; middle aged; clinical trial; neutropenia; disease free survival; antineoplastic agent; antineoplastic combined chemotherapy protocols; drug administration schedule; acute lymphoblastic leukemia; blood; feasibility study; feasibility studies; chemically induced disorder; asparaginase; sepsis; precursor cell lymphoblastic leukemia-lymphoma; hyperbilirubinemia; drug administration; infusions, intravenous; polyethylene glycols; induction chemotherapy; intravenous drug administration; drug-induced liver injury; macrogol derivative; asparaginase macrogol; toxic hepatitis; humans; human; male; female; article
Journal Title: Journal of Clinical Oncology
Volume: 32
Issue: 9
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2014-03-20
Start Page: 905
End Page: 911
Language: English
DOI: 10.1200/jco.2013.50.2708
PROVIDER: scopus
PUBMED: 24516026
DOI/URL:
Notes: J. Clin. Oncol. -- Export Date: 2 June 2014 -- Source: Scopus
Altmetric Score
MSK Authors
  1. Matthew Alexander Lunning
    26 Lunning
  2. Martin Stuart Tallman
    408 Tallman
  3. Jae Hong Park
    132 Park
  4. Dan Douer
    80 Douer
  5. Patrick William Burke
    7 Burke