An open‐label, multicenter study of polyethylene glycol‐L‐asparaginase for the treatment of acute lymphoblastic leukemia

Lawrence J. Ettinger, Joanne Kurtzberg, P. A. Voǔte, Herbert Jürgens, Steven L. Halpern

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

Background. L‐asparaginase has been a mainstay of therapy along with vincristine and prednisone in the treatment of acute lymphoblastic leukemia (ALL) in children for almost 30 years. Because L‐asparaginase is a foreign protein, the potential exists for severe, dose‐limiting hypersensitivity reactions. To reduce this toxicity, L‐asparaginase has been linked with polyethylene glycol (PEG). Methods. Patients with ALL in relapse were entered in a Phase II, open‐label clinical trial (ASP‐201A) to evaluate the toxicity and efficacy of PEG‐L‐asparaginase. PEG‐L‐asparaginase has demonstrated potential low immunogenicity and a prolonged plasma half‐life relative to native enzyme. PEG‐L‐asparaginase (2000 IU/m2 every 2 weeks) was used as single‐agent induction therapy during an initial 14‐day investigational window. Thereafter, the regimen consisted of PEG‐L‐asparaginase, vincristine, and prednisone. Patients also were allowed to receive doxorubicin and intrathecal chemotherapy beginning on day 14. All patients had been treated previously with one or more courses of native L‐asparaginase; one of these patients was hypersensitive to L‐asparaginase at enrollment. Results. During the 14‐day investigational window with PEG‐L‐asparaginase monotherapy, 22% of patients examined achieved a complete or partial remission. By completion, of the 35‐day induction period, 78% (or 14 of 18) of evaluated patients achieved complete or partial remission. Anaphylaxis did not occur during treatment. Mild urticaria and mild local allergic reactions occurred in five patients but did not cause discontinuation of treatment. The incidence of hyperglycemia and pancreatitis was less than expected from historic data published for previous studies with native L‐asparaginase. Conclusions. As administered in this study, PEG‐L‐asparaginase can be given safely with a spectrum of toxicity similar to that of native L‐asparaginase. Single‐agent activity was documented in patients with ALL in bone marrow relapse. Cancer 1995;75:1176–81.

Original languageEnglish (US)
Pages (from-to)1176-1181
Number of pages6
JournalCancer
Volume75
Issue number5
DOIs
StatePublished - Mar 1 1995
Externally publishedYes

Fingerprint

Polyethylene
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Multicenter Studies
Vincristine
Therapeutics
Prednisone
Hypersensitivity
Recurrence
Phase II Clinical Trials
Urticaria
Anaphylaxis
Hyperglycemia
Pancreatitis
Doxorubicin
Half-Life
Bone Marrow
Drug Therapy
Incidence
Enzymes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Ettinger, Lawrence J. ; Kurtzberg, Joanne ; Voǔte, P. A. ; Jürgens, Herbert ; Halpern, Steven L. / An open‐label, multicenter study of polyethylene glycol‐L‐asparaginase for the treatment of acute lymphoblastic leukemia. In: Cancer. 1995 ; Vol. 75, No. 5. pp. 1176-1181.
@article{a0965ab604364805b649ba17ba7060bb,
title = "An open‐label, multicenter study of polyethylene glycol‐L‐asparaginase for the treatment of acute lymphoblastic leukemia",
abstract = "Background. L‐asparaginase has been a mainstay of therapy along with vincristine and prednisone in the treatment of acute lymphoblastic leukemia (ALL) in children for almost 30 years. Because L‐asparaginase is a foreign protein, the potential exists for severe, dose‐limiting hypersensitivity reactions. To reduce this toxicity, L‐asparaginase has been linked with polyethylene glycol (PEG). Methods. Patients with ALL in relapse were entered in a Phase II, open‐label clinical trial (ASP‐201A) to evaluate the toxicity and efficacy of PEG‐L‐asparaginase. PEG‐L‐asparaginase has demonstrated potential low immunogenicity and a prolonged plasma half‐life relative to native enzyme. PEG‐L‐asparaginase (2000 IU/m2 every 2 weeks) was used as single‐agent induction therapy during an initial 14‐day investigational window. Thereafter, the regimen consisted of PEG‐L‐asparaginase, vincristine, and prednisone. Patients also were allowed to receive doxorubicin and intrathecal chemotherapy beginning on day 14. All patients had been treated previously with one or more courses of native L‐asparaginase; one of these patients was hypersensitive to L‐asparaginase at enrollment. Results. During the 14‐day investigational window with PEG‐L‐asparaginase monotherapy, 22{\%} of patients examined achieved a complete or partial remission. By completion, of the 35‐day induction period, 78{\%} (or 14 of 18) of evaluated patients achieved complete or partial remission. Anaphylaxis did not occur during treatment. Mild urticaria and mild local allergic reactions occurred in five patients but did not cause discontinuation of treatment. The incidence of hyperglycemia and pancreatitis was less than expected from historic data published for previous studies with native L‐asparaginase. Conclusions. As administered in this study, PEG‐L‐asparaginase can be given safely with a spectrum of toxicity similar to that of native L‐asparaginase. Single‐agent activity was documented in patients with ALL in bone marrow relapse. Cancer 1995;75:1176–81.",
author = "Ettinger, {Lawrence J.} and Joanne Kurtzberg and Voǔte, {P. A.} and Herbert J{\"u}rgens and Halpern, {Steven L.}",
year = "1995",
month = "3",
day = "1",
doi = "10.1002/1097-0142(19950301)75:5<1176::AID-CNCR2820750519>3.0.CO;2-Y",
language = "English (US)",
volume = "75",
pages = "1176--1181",
journal = "Cancer",
issn = "0008-543X",
publisher = "John Wiley and Sons Inc.",
number = "5",

}

An open‐label, multicenter study of polyethylene glycol‐L‐asparaginase for the treatment of acute lymphoblastic leukemia. / Ettinger, Lawrence J.; Kurtzberg, Joanne; Voǔte, P. A.; Jürgens, Herbert; Halpern, Steven L.

In: Cancer, Vol. 75, No. 5, 01.03.1995, p. 1176-1181.

Research output: Contribution to journalArticle

TY - JOUR

T1 - An open‐label, multicenter study of polyethylene glycol‐L‐asparaginase for the treatment of acute lymphoblastic leukemia

AU - Ettinger, Lawrence J.

AU - Kurtzberg, Joanne

AU - Voǔte, P. A.

AU - Jürgens, Herbert

AU - Halpern, Steven L.

PY - 1995/3/1

Y1 - 1995/3/1

N2 - Background. L‐asparaginase has been a mainstay of therapy along with vincristine and prednisone in the treatment of acute lymphoblastic leukemia (ALL) in children for almost 30 years. Because L‐asparaginase is a foreign protein, the potential exists for severe, dose‐limiting hypersensitivity reactions. To reduce this toxicity, L‐asparaginase has been linked with polyethylene glycol (PEG). Methods. Patients with ALL in relapse were entered in a Phase II, open‐label clinical trial (ASP‐201A) to evaluate the toxicity and efficacy of PEG‐L‐asparaginase. PEG‐L‐asparaginase has demonstrated potential low immunogenicity and a prolonged plasma half‐life relative to native enzyme. PEG‐L‐asparaginase (2000 IU/m2 every 2 weeks) was used as single‐agent induction therapy during an initial 14‐day investigational window. Thereafter, the regimen consisted of PEG‐L‐asparaginase, vincristine, and prednisone. Patients also were allowed to receive doxorubicin and intrathecal chemotherapy beginning on day 14. All patients had been treated previously with one or more courses of native L‐asparaginase; one of these patients was hypersensitive to L‐asparaginase at enrollment. Results. During the 14‐day investigational window with PEG‐L‐asparaginase monotherapy, 22% of patients examined achieved a complete or partial remission. By completion, of the 35‐day induction period, 78% (or 14 of 18) of evaluated patients achieved complete or partial remission. Anaphylaxis did not occur during treatment. Mild urticaria and mild local allergic reactions occurred in five patients but did not cause discontinuation of treatment. The incidence of hyperglycemia and pancreatitis was less than expected from historic data published for previous studies with native L‐asparaginase. Conclusions. As administered in this study, PEG‐L‐asparaginase can be given safely with a spectrum of toxicity similar to that of native L‐asparaginase. Single‐agent activity was documented in patients with ALL in bone marrow relapse. Cancer 1995;75:1176–81.

AB - Background. L‐asparaginase has been a mainstay of therapy along with vincristine and prednisone in the treatment of acute lymphoblastic leukemia (ALL) in children for almost 30 years. Because L‐asparaginase is a foreign protein, the potential exists for severe, dose‐limiting hypersensitivity reactions. To reduce this toxicity, L‐asparaginase has been linked with polyethylene glycol (PEG). Methods. Patients with ALL in relapse were entered in a Phase II, open‐label clinical trial (ASP‐201A) to evaluate the toxicity and efficacy of PEG‐L‐asparaginase. PEG‐L‐asparaginase has demonstrated potential low immunogenicity and a prolonged plasma half‐life relative to native enzyme. PEG‐L‐asparaginase (2000 IU/m2 every 2 weeks) was used as single‐agent induction therapy during an initial 14‐day investigational window. Thereafter, the regimen consisted of PEG‐L‐asparaginase, vincristine, and prednisone. Patients also were allowed to receive doxorubicin and intrathecal chemotherapy beginning on day 14. All patients had been treated previously with one or more courses of native L‐asparaginase; one of these patients was hypersensitive to L‐asparaginase at enrollment. Results. During the 14‐day investigational window with PEG‐L‐asparaginase monotherapy, 22% of patients examined achieved a complete or partial remission. By completion, of the 35‐day induction period, 78% (or 14 of 18) of evaluated patients achieved complete or partial remission. Anaphylaxis did not occur during treatment. Mild urticaria and mild local allergic reactions occurred in five patients but did not cause discontinuation of treatment. The incidence of hyperglycemia and pancreatitis was less than expected from historic data published for previous studies with native L‐asparaginase. Conclusions. As administered in this study, PEG‐L‐asparaginase can be given safely with a spectrum of toxicity similar to that of native L‐asparaginase. Single‐agent activity was documented in patients with ALL in bone marrow relapse. Cancer 1995;75:1176–81.

UR - http://www.scopus.com/inward/record.url?scp=0028911354&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028911354&partnerID=8YFLogxK

U2 - 10.1002/1097-0142(19950301)75:5<1176::AID-CNCR2820750519>3.0.CO;2-Y

DO - 10.1002/1097-0142(19950301)75:5<1176::AID-CNCR2820750519>3.0.CO;2-Y

M3 - Article

C2 - 7850718

AN - SCOPUS:0028911354

VL - 75

SP - 1176

EP - 1181

JO - Cancer

JF - Cancer

SN - 0008-543X

IS - 5

ER -