Abstract | PURPOSE:
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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.
|
Authors | Dan Douer, Ibrahim Aldoss, Matthew A Lunning, Patrick W Burke, Laleh Ramezani, Lisa Mark, Janice Vrona, Jae H Park, Martin S Tallman, Vassilios I Avramis, Vinod Pullarkat, Ann M Mohrbacher |
Journal | Journal of clinical oncology : official journal of the American Society of Clinical Oncology
(J Clin Oncol)
Vol. 32
Issue 9
Pg. 905-11
(Mar 20 2014)
ISSN: 1527-7755 [Electronic] United States |
PMID | 24516026
(Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Polyethylene Glycols
- pegaspargase
- Asparaginase
|
Topics |
- Adult
- Antineoplastic Combined Chemotherapy Protocols
(therapeutic use)
- Asparaginase
(administration & dosage, adverse effects, blood, pharmacokinetics)
- Chemical and Drug Induced Liver Injury
(etiology)
- Disease-Free Survival
- Drug Administration Schedule
- Feasibility Studies
- Female
- Humans
- Hyperbilirubinemia
(chemically induced)
- Induction Chemotherapy
- Infusions, Intravenous
- Male
- Middle Aged
- Neutropenia
(chemically induced, complications)
- Polyethylene Glycols
(administration & dosage, adverse effects, pharmacokinetics)
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
(blood, diagnosis, drug therapy)
- Sepsis
(etiology)
- Treatment Outcome
|