Treatment of Philadelphia chromosome-positive chronic myelogenous leukemia with weekly polyethylene glycol formulation of interferon-alpha-2b and low-dose cytosine arabinoside

Guillermo Garcia-Manero, Moshe Talpaz, Francis J. Giles, Jorge Cortes, Stefan Faderl, Susan O'Brien, Deborah Thomas, Srdan Verstovsek, Mary Beth Rios, Jianquin Shan, Alessandra Ferrajoli, William Wierda, Hagop M. Kantarjian

Research output: Contribution to journalArticle

Abstract

BACKGROUND. To evaluate the activity and toxicity of weekly Schering 54301, a polyethylene glycol formulation of interferon-α-2b (PEG-IFN-α-2b), with cytosine arabinoside (ara-C) in patients with chronic myelogenous leukemia (CML). METHODS. Seventy-six patients with Philadelphia chromosome (Ph)-positive early chronic-phase CML were treated with the combination of PEG-IFN-α-2b and ara-C (10 mg daily subcutaneously [s.c.]). The starting dose of PEG-IFN-α-2b was 6 μg/kg s.c. weekly in the first 24 patients but was reduced to 4.5 μg/kg in the next 52 patients. RESULTS. Overall, 73% of patients had a complete hematologic response, 35% of patients had a major cytogenetic response (Ph < 35%), and 21% of patients had a complete cytogenetic response (Ph = 0%). With a median follow-up of 19 months, the estimated 2-year survival rate was 89%. Therapy was discontinued in 24% of patients due to Grade III-IV toxicity. Frequent severe side effects that required dose reductions included neutropenia (49%), fatigue (43%), and neurologic toxicity (17%). The median PEG-IFN-α-2b and ara-C doses delivered were 3 μg/kg weekly and 7.5 mg daily, respectively, at 12 months of therapy. The activity and toxicity profiles of this combination was similar to those observed in historical patients treated with IFN-α and cytarabine. CONCLUSIONS. The combination of PEG-IFN-α-2b and ara-C is active but has significant toxicity in patients with chronic-phase CML at the dose schedule used. The recommended dose of PEG-IFN-α-2b in future combination studies is 3 μg/kg or less.

Original languageEnglish (US)
Pages (from-to)3010-3016
Number of pages7
JournalCancer
Volume97
Issue number12
DOIs
StatePublished - Jun 15 2003
Externally publishedYes

Fingerprint

Philadelphia Chromosome
Cytarabine
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Interferons
Leukemia, Myeloid, Chronic Phase
Therapeutics
Cytogenetics
peginterferon alfa-2b
Neutropenia
Nervous System
Fatigue
Appointments and Schedules
Survival Rate

Keywords

  • Chronic myelogenous leukemia
  • Cytogenetic response
  • Cytosine arabinoside
  • Polyethylene glycol interferon

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Treatment of Philadelphia chromosome-positive chronic myelogenous leukemia with weekly polyethylene glycol formulation of interferon-alpha-2b and low-dose cytosine arabinoside. / Garcia-Manero, Guillermo; Talpaz, Moshe; Giles, Francis J.; Cortes, Jorge; Faderl, Stefan; O'Brien, Susan; Thomas, Deborah; Verstovsek, Srdan; Rios, Mary Beth; Shan, Jianquin; Ferrajoli, Alessandra; Wierda, William; Kantarjian, Hagop M.

In: Cancer, Vol. 97, No. 12, 15.06.2003, p. 3010-3016.

Research output: Contribution to journalArticle

Garcia-Manero, G, Talpaz, M, Giles, FJ, Cortes, J, Faderl, S, O'Brien, S, Thomas, D, Verstovsek, S, Rios, MB, Shan, J, Ferrajoli, A, Wierda, W & Kantarjian, HM 2003, 'Treatment of Philadelphia chromosome-positive chronic myelogenous leukemia with weekly polyethylene glycol formulation of interferon-alpha-2b and low-dose cytosine arabinoside', Cancer, vol. 97, no. 12, pp. 3010-3016. https://doi.org/10.1002/cncr.11424
Garcia-Manero, Guillermo ; Talpaz, Moshe ; Giles, Francis J. ; Cortes, Jorge ; Faderl, Stefan ; O'Brien, Susan ; Thomas, Deborah ; Verstovsek, Srdan ; Rios, Mary Beth ; Shan, Jianquin ; Ferrajoli, Alessandra ; Wierda, William ; Kantarjian, Hagop M. / Treatment of Philadelphia chromosome-positive chronic myelogenous leukemia with weekly polyethylene glycol formulation of interferon-alpha-2b and low-dose cytosine arabinoside. In: Cancer. 2003 ; Vol. 97, No. 12. pp. 3010-3016.
@article{84d620a46aef4ffe82c6f3967841fab3,
title = "Treatment of Philadelphia chromosome-positive chronic myelogenous leukemia with weekly polyethylene glycol formulation of interferon-alpha-2b and low-dose cytosine arabinoside",
abstract = "BACKGROUND. To evaluate the activity and toxicity of weekly Schering 54301, a polyethylene glycol formulation of interferon-α-2b (PEG-IFN-α-2b), with cytosine arabinoside (ara-C) in patients with chronic myelogenous leukemia (CML). METHODS. Seventy-six patients with Philadelphia chromosome (Ph)-positive early chronic-phase CML were treated with the combination of PEG-IFN-α-2b and ara-C (10 mg daily subcutaneously [s.c.]). The starting dose of PEG-IFN-α-2b was 6 μg/kg s.c. weekly in the first 24 patients but was reduced to 4.5 μg/kg in the next 52 patients. RESULTS. Overall, 73{\%} of patients had a complete hematologic response, 35{\%} of patients had a major cytogenetic response (Ph < 35{\%}), and 21{\%} of patients had a complete cytogenetic response (Ph = 0{\%}). With a median follow-up of 19 months, the estimated 2-year survival rate was 89{\%}. Therapy was discontinued in 24{\%} of patients due to Grade III-IV toxicity. Frequent severe side effects that required dose reductions included neutropenia (49{\%}), fatigue (43{\%}), and neurologic toxicity (17{\%}). The median PEG-IFN-α-2b and ara-C doses delivered were 3 μg/kg weekly and 7.5 mg daily, respectively, at 12 months of therapy. The activity and toxicity profiles of this combination was similar to those observed in historical patients treated with IFN-α and cytarabine. CONCLUSIONS. The combination of PEG-IFN-α-2b and ara-C is active but has significant toxicity in patients with chronic-phase CML at the dose schedule used. The recommended dose of PEG-IFN-α-2b in future combination studies is 3 μg/kg or less.",
keywords = "Chronic myelogenous leukemia, Cytogenetic response, Cytosine arabinoside, Polyethylene glycol interferon",
author = "Guillermo Garcia-Manero and Moshe Talpaz and Giles, {Francis J.} and Jorge Cortes and Stefan Faderl and Susan O'Brien and Deborah Thomas and Srdan Verstovsek and Rios, {Mary Beth} and Jianquin Shan and Alessandra Ferrajoli and William Wierda and Kantarjian, {Hagop M.}",
year = "2003",
month = "6",
day = "15",
doi = "10.1002/cncr.11424",
language = "English (US)",
volume = "97",
pages = "3010--3016",
journal = "Cancer",
issn = "0008-543X",
publisher = "John Wiley and Sons Inc.",
number = "12",

}

TY - JOUR

T1 - Treatment of Philadelphia chromosome-positive chronic myelogenous leukemia with weekly polyethylene glycol formulation of interferon-alpha-2b and low-dose cytosine arabinoside

AU - Garcia-Manero, Guillermo

AU - Talpaz, Moshe

AU - Giles, Francis J.

AU - Cortes, Jorge

AU - Faderl, Stefan

AU - O'Brien, Susan

AU - Thomas, Deborah

AU - Verstovsek, Srdan

AU - Rios, Mary Beth

AU - Shan, Jianquin

AU - Ferrajoli, Alessandra

AU - Wierda, William

AU - Kantarjian, Hagop M.

PY - 2003/6/15

Y1 - 2003/6/15

N2 - BACKGROUND. To evaluate the activity and toxicity of weekly Schering 54301, a polyethylene glycol formulation of interferon-α-2b (PEG-IFN-α-2b), with cytosine arabinoside (ara-C) in patients with chronic myelogenous leukemia (CML). METHODS. Seventy-six patients with Philadelphia chromosome (Ph)-positive early chronic-phase CML were treated with the combination of PEG-IFN-α-2b and ara-C (10 mg daily subcutaneously [s.c.]). The starting dose of PEG-IFN-α-2b was 6 μg/kg s.c. weekly in the first 24 patients but was reduced to 4.5 μg/kg in the next 52 patients. RESULTS. Overall, 73% of patients had a complete hematologic response, 35% of patients had a major cytogenetic response (Ph < 35%), and 21% of patients had a complete cytogenetic response (Ph = 0%). With a median follow-up of 19 months, the estimated 2-year survival rate was 89%. Therapy was discontinued in 24% of patients due to Grade III-IV toxicity. Frequent severe side effects that required dose reductions included neutropenia (49%), fatigue (43%), and neurologic toxicity (17%). The median PEG-IFN-α-2b and ara-C doses delivered were 3 μg/kg weekly and 7.5 mg daily, respectively, at 12 months of therapy. The activity and toxicity profiles of this combination was similar to those observed in historical patients treated with IFN-α and cytarabine. CONCLUSIONS. The combination of PEG-IFN-α-2b and ara-C is active but has significant toxicity in patients with chronic-phase CML at the dose schedule used. The recommended dose of PEG-IFN-α-2b in future combination studies is 3 μg/kg or less.

AB - BACKGROUND. To evaluate the activity and toxicity of weekly Schering 54301, a polyethylene glycol formulation of interferon-α-2b (PEG-IFN-α-2b), with cytosine arabinoside (ara-C) in patients with chronic myelogenous leukemia (CML). METHODS. Seventy-six patients with Philadelphia chromosome (Ph)-positive early chronic-phase CML were treated with the combination of PEG-IFN-α-2b and ara-C (10 mg daily subcutaneously [s.c.]). The starting dose of PEG-IFN-α-2b was 6 μg/kg s.c. weekly in the first 24 patients but was reduced to 4.5 μg/kg in the next 52 patients. RESULTS. Overall, 73% of patients had a complete hematologic response, 35% of patients had a major cytogenetic response (Ph < 35%), and 21% of patients had a complete cytogenetic response (Ph = 0%). With a median follow-up of 19 months, the estimated 2-year survival rate was 89%. Therapy was discontinued in 24% of patients due to Grade III-IV toxicity. Frequent severe side effects that required dose reductions included neutropenia (49%), fatigue (43%), and neurologic toxicity (17%). The median PEG-IFN-α-2b and ara-C doses delivered were 3 μg/kg weekly and 7.5 mg daily, respectively, at 12 months of therapy. The activity and toxicity profiles of this combination was similar to those observed in historical patients treated with IFN-α and cytarabine. CONCLUSIONS. The combination of PEG-IFN-α-2b and ara-C is active but has significant toxicity in patients with chronic-phase CML at the dose schedule used. The recommended dose of PEG-IFN-α-2b in future combination studies is 3 μg/kg or less.

KW - Chronic myelogenous leukemia

KW - Cytogenetic response

KW - Cytosine arabinoside

KW - Polyethylene glycol interferon

UR - http://www.scopus.com/inward/record.url?scp=0037672700&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037672700&partnerID=8YFLogxK

U2 - 10.1002/cncr.11424

DO - 10.1002/cncr.11424

M3 - Article

C2 - 12784336

AN - SCOPUS:0037672700

VL - 97

SP - 3010

EP - 3016

JO - Cancer

JF - Cancer

SN - 0008-543X

IS - 12

ER -