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Medline ® Abstract for Reference 203

of '肝病患者的化疗肝毒性和剂量调整'

203
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Pharmacokinetics-based integration of multiple doses of intravenous pegaspargase in a pediatric regimen for adults with newly diagnosed acute lymphoblastic leukemia.
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Douer D, Aldoss I, Lunning MA, Burke PW, Ramezani L, Mark L, Vrona J, Park JH, Tallman MS, Avramis VI, Pullarkat V, Mohrbacher AM
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J Clin Oncol. 2014 Mar;32(9):905-11. Epub 2014 Feb 10.
 
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 otherchemotherapy 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.
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Dan Douer, Matthew A. Lunning, Patrick W. Burke, Jae H. Park, and Martin S. Tallman, Memorial Sloan-Kettering Cancer Center, Weill Cornell Medical College, New York, NY; Ibrahim Aldoss, Laleh Ramezani, Lisa Mark, Janice Vrona, Vinod Pullarkat, and Ann M. Mohrbacher, Keck School of Medicine, University of Southern California; and Vassilios I. Avramis, Children's Hospital of Los Angeles, University of Southern California, Los Angeles, CA.
PMID