Pharmacokinetic and Pharmacodynamic Properties of Calaspargase Pegol Escherichia coli L-Asparaginase in the Treatment of Patients With Acute Lymphoblastic Leukemia: Results From Children's Oncology Group Study AALL07P4

被引：94

作者：

Angiolillo, Anne L. ^{[1
]}

Schore, Reuven J. ^{[1
]}

Devidas, Meenakshi ^{[2
]}

Borowitz, Michael J. ^{[4
]}

Carroll, Andrew J. ^{[6
]}

Gastier-Foster, Julie M. ^{[7
,8
,9
]}

Heerema, Nyla A. ^{[7
]}

Keilani, Taha ^{[5
]}

Lane, Ashley R. ^{[1
]}

Loh, Mignon L. ^{[10
]}

Reaman, Gregory H. ^{[1
]}

Adamson, Peter C. ^{[11
]}

Wood, Brent ^{[12
]}

Wood, Charlotte ^{[3
]}

Zheng, Hao W. ^{[3
]}

Raetz, Elizabeth A. ^{[13
]}

Winick, Naomi J. ^{[14
]}

Carroll, William L. ^{[13
]}

Hunger, Stephen P. ^{[15
,16
]}

机构：

[1] Childrens Natl Med Ctr, Washington, DC 20010 USA

[2] Univ Florida, Coll Med, Coll Publ Hlth & Hlth Profess, Gainesville, FL 32611 USA

[3] Childrens Oncol Grp, Gainesville, FL USA

[4] Johns Hopkins Med Inst, Baltimore, MD 21205 USA

[5] Sigma Tau Pharmaceut, Gaithersburg, MD USA

[6] Univ Alabama Birmingham, Birmingham, AL USA

[7] Ohio State Univ, Wexner Med Ctr, Columbus, OH 43210 USA

[8] Ohio State Univ, Coll Med, Columbus, OH 43210 USA

[9] Nationwide Childrens Hosp, Columbus, OH USA

[10] Univ Calif San Francisco, San Francisco, CA 94143 USA

[11] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA

[12] Univ Washington, Seattle, WA 98195 USA

[13] NYU, Langone Med Ctr, Inst Canc, New York, NY USA

[14] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA

[15] Childrens Hosp Colorado, Aurora, CO USA

[16] Univ Colorado, Sch Med, Aurora, CO USA

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2014年 / 32卷 / 34期

关键词：

MINIMAL RESIDUAL DISEASE; GUINEA PIG SERUM; ERWINIA ASPARAGINASE; THERAPY;

D O I：

10.1200/JCO.2014.55.5763

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Purpose Asparaginase is a critical agent used to treat acute lymphoblastic leukemia (ALL). Pegaspargase (SS-PEG), a pegylated form of Escherichia coli L-asparaginase with a succinimidyl succinate (SS) linker, is the first-line asparaginase product used in Children's Oncology Group (COG) ALL trials. Calaspargase pegol (SC-PEG) replaces the SS linker in SS-PEG with a succinimidyl carbamate linker, creating a more stable molecule. COG AALL07P4 was designed to determine the pharmacokinetic and pharmacodynamic comparability of SC-PEG to SS-PEG in patients with newly diagnosed high-risk (HR) B-cell ALL. Patients and Methods A total of 165 evaluable patients were randomly assigned at a 2:1 ratio to receive SC-PEG at 2,100 (SC-PEG2100; n = 69) or 2,500 IU/m(2) (SC-PEG2500; n = 42) versus SS-PEG 2,500 IU/m(2) (SS-PEG2500; n = 54) as part of an otherwise identical chemotherapy regimen. The groups were similar demographically, except more female patients received SC-PEG2500. Results The mean half-life of plasma asparaginase activity for both SC-PEG doses was approximately 2.5 x longer than that of SS-PEG2500. The total systemic exposure, as defined by induction area under the curve from time 0 to 25 days, was greater with SC-PEG2500 than with SS-PEG2500 or SC-PEG2100. The proportion of patients with plasma asparaginase activity >= 100 mIU/mL and >= 400 mIU/mL was higher in patients who received SC-PEG as compared with SS-PEG2500. After one dose of pegylated asparaginase on induction day 4, plasma asparagine was undetectable for 11 days for SS-PEG2500 and 18 days for both SC-PEG groups. Conclusion SC-PEG2500 achieves a significantly longer period of asparaginase activity above defined thresholds and asparagine depletion compared with SS-PEG2500 and has a comparable toxicity profile in children with HR B-cell ALL. (C) 2014 by American Society of Clinical Oncology

引用

页码：3874 / U276

页数：10

共 20 条

[1] Dose reduction of asparaginase under pharmacokinetic and pharmacodynamic control during induction therapy in children with acute lymphoblastic leukaemia [J].