Dasatinib in imatinib-resistant or imatinib-intolerant chronic myeloid leukemia in blast phase after 2 years of follow-up in a phase 3 study: Efficacy and tolerability of 140 milligrams once daily and 70 milligrams twice daily

Giuseppe Saglio, Andreas Hochhaus, Yeow Tee Goh, Tamas Masszi, Ricardo Pasquini, Frederic Maloisel, Philipp Erben, Jorge Cortes, Ronald Paquette, M. Brigid Bradley-Garelik, Chao Zhu, Herve Dombret

Research output: Contribution to journalArticle

Abstract

BACKGROUND: In a phase 3 study, the authors assessed the effects of dasatinib at doses of 140 mg once daily and 70 mg twice daily in patients who had either chronic myeloid leukemia (CML) in advanced phases or Philadelphia chromosome-positive acute lymphoblastic leukemia and were resistant or intolerant to imatinib. In the current report, the results for patients with CML in blast phase after 2 years of follow-up are reported. METHODS: Patients were stratified according to whether they had CML in myeloid blast phase (MBP-CML) or in lymphoid blast phase (LBP-CML) and were randomized (1:1) within each stratum to receive either oral dasatinib 140 mg once daily or 70 mg twice daily. RESULTS: In patients with MBP-CML, the major hematologic response rate was 28% for both regimens; and, in patients with LBP-CML, the major hematologic response rate was 42% for once-daily dasatinib and 32% for twice-daily dasatinib. The major cytogenetic response rates were 25% for once-daily dasatinib and 28% for twice-daily dasatinib in patients with MBP-CML, and the respective rates in patients with LBP-CML were 50% and 40%. The overall survival rate at 24 months was 24% for once-daily dasatinib and 28% for twice-daily dasatinib in patients with MBP-CML, and the respective values in patients with LBP-CML were 21% and 16%. Adverse events indicated a trend toward improved tolerability for the once-daily regimen. CONCLUSIONS: The current results suggested that dasatinib 140 mg once daily had similar efficacy and improved tolerability relative to the 70-mg twice-daily regimen in patients with imatinib-resistant, blast phase CML.

Original languageEnglish (US)
Pages (from-to)3852-3861
Number of pages10
JournalCancer
Volume116
Issue number16
DOIs
StatePublished - Aug 15 2010
Externally publishedYes

Fingerprint

Blast Crisis
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Imatinib Mesylate
Dasatinib
Philadelphia Chromosome
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Cytogenetics

Keywords

  • Blast crisis
  • Chronic myeloid leukemia
  • Dasatinib
  • Drug resistance
  • Imatinib

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Dasatinib in imatinib-resistant or imatinib-intolerant chronic myeloid leukemia in blast phase after 2 years of follow-up in a phase 3 study : Efficacy and tolerability of 140 milligrams once daily and 70 milligrams twice daily. / Saglio, Giuseppe; Hochhaus, Andreas; Goh, Yeow Tee; Masszi, Tamas; Pasquini, Ricardo; Maloisel, Frederic; Erben, Philipp; Cortes, Jorge; Paquette, Ronald; Bradley-Garelik, M. Brigid; Zhu, Chao; Dombret, Herve.

In: Cancer, Vol. 116, No. 16, 15.08.2010, p. 3852-3861.

Research output: Contribution to journalArticle

Saglio, Giuseppe ; Hochhaus, Andreas ; Goh, Yeow Tee ; Masszi, Tamas ; Pasquini, Ricardo ; Maloisel, Frederic ; Erben, Philipp ; Cortes, Jorge ; Paquette, Ronald ; Bradley-Garelik, M. Brigid ; Zhu, Chao ; Dombret, Herve. / Dasatinib in imatinib-resistant or imatinib-intolerant chronic myeloid leukemia in blast phase after 2 years of follow-up in a phase 3 study : Efficacy and tolerability of 140 milligrams once daily and 70 milligrams twice daily. In: Cancer. 2010 ; Vol. 116, No. 16. pp. 3852-3861.
@article{ea0c1d10c8f54f4cb42673e05d33a49d,
title = "Dasatinib in imatinib-resistant or imatinib-intolerant chronic myeloid leukemia in blast phase after 2 years of follow-up in a phase 3 study: Efficacy and tolerability of 140 milligrams once daily and 70 milligrams twice daily",
abstract = "BACKGROUND: In a phase 3 study, the authors assessed the effects of dasatinib at doses of 140 mg once daily and 70 mg twice daily in patients who had either chronic myeloid leukemia (CML) in advanced phases or Philadelphia chromosome-positive acute lymphoblastic leukemia and were resistant or intolerant to imatinib. In the current report, the results for patients with CML in blast phase after 2 years of follow-up are reported. METHODS: Patients were stratified according to whether they had CML in myeloid blast phase (MBP-CML) or in lymphoid blast phase (LBP-CML) and were randomized (1:1) within each stratum to receive either oral dasatinib 140 mg once daily or 70 mg twice daily. RESULTS: In patients with MBP-CML, the major hematologic response rate was 28{\%} for both regimens; and, in patients with LBP-CML, the major hematologic response rate was 42{\%} for once-daily dasatinib and 32{\%} for twice-daily dasatinib. The major cytogenetic response rates were 25{\%} for once-daily dasatinib and 28{\%} for twice-daily dasatinib in patients with MBP-CML, and the respective rates in patients with LBP-CML were 50{\%} and 40{\%}. The overall survival rate at 24 months was 24{\%} for once-daily dasatinib and 28{\%} for twice-daily dasatinib in patients with MBP-CML, and the respective values in patients with LBP-CML were 21{\%} and 16{\%}. Adverse events indicated a trend toward improved tolerability for the once-daily regimen. CONCLUSIONS: The current results suggested that dasatinib 140 mg once daily had similar efficacy and improved tolerability relative to the 70-mg twice-daily regimen in patients with imatinib-resistant, blast phase CML.",
keywords = "Blast crisis, Chronic myeloid leukemia, Dasatinib, Drug resistance, Imatinib",
author = "Giuseppe Saglio and Andreas Hochhaus and Goh, {Yeow Tee} and Tamas Masszi and Ricardo Pasquini and Frederic Maloisel and Philipp Erben and Jorge Cortes and Ronald Paquette and Bradley-Garelik, {M. Brigid} and Chao Zhu and Herve Dombret",
year = "2010",
month = "8",
day = "15",
doi = "10.1002/cncr.25123",
language = "English (US)",
volume = "116",
pages = "3852--3861",
journal = "Cancer",
issn = "0008-543X",
publisher = "John Wiley and Sons Inc.",
number = "16",

}

TY - JOUR

T1 - Dasatinib in imatinib-resistant or imatinib-intolerant chronic myeloid leukemia in blast phase after 2 years of follow-up in a phase 3 study

T2 - Efficacy and tolerability of 140 milligrams once daily and 70 milligrams twice daily

AU - Saglio, Giuseppe

AU - Hochhaus, Andreas

AU - Goh, Yeow Tee

AU - Masszi, Tamas

AU - Pasquini, Ricardo

AU - Maloisel, Frederic

AU - Erben, Philipp

AU - Cortes, Jorge

AU - Paquette, Ronald

AU - Bradley-Garelik, M. Brigid

AU - Zhu, Chao

AU - Dombret, Herve

PY - 2010/8/15

Y1 - 2010/8/15

N2 - BACKGROUND: In a phase 3 study, the authors assessed the effects of dasatinib at doses of 140 mg once daily and 70 mg twice daily in patients who had either chronic myeloid leukemia (CML) in advanced phases or Philadelphia chromosome-positive acute lymphoblastic leukemia and were resistant or intolerant to imatinib. In the current report, the results for patients with CML in blast phase after 2 years of follow-up are reported. METHODS: Patients were stratified according to whether they had CML in myeloid blast phase (MBP-CML) or in lymphoid blast phase (LBP-CML) and were randomized (1:1) within each stratum to receive either oral dasatinib 140 mg once daily or 70 mg twice daily. RESULTS: In patients with MBP-CML, the major hematologic response rate was 28% for both regimens; and, in patients with LBP-CML, the major hematologic response rate was 42% for once-daily dasatinib and 32% for twice-daily dasatinib. The major cytogenetic response rates were 25% for once-daily dasatinib and 28% for twice-daily dasatinib in patients with MBP-CML, and the respective rates in patients with LBP-CML were 50% and 40%. The overall survival rate at 24 months was 24% for once-daily dasatinib and 28% for twice-daily dasatinib in patients with MBP-CML, and the respective values in patients with LBP-CML were 21% and 16%. Adverse events indicated a trend toward improved tolerability for the once-daily regimen. CONCLUSIONS: The current results suggested that dasatinib 140 mg once daily had similar efficacy and improved tolerability relative to the 70-mg twice-daily regimen in patients with imatinib-resistant, blast phase CML.

AB - BACKGROUND: In a phase 3 study, the authors assessed the effects of dasatinib at doses of 140 mg once daily and 70 mg twice daily in patients who had either chronic myeloid leukemia (CML) in advanced phases or Philadelphia chromosome-positive acute lymphoblastic leukemia and were resistant or intolerant to imatinib. In the current report, the results for patients with CML in blast phase after 2 years of follow-up are reported. METHODS: Patients were stratified according to whether they had CML in myeloid blast phase (MBP-CML) or in lymphoid blast phase (LBP-CML) and were randomized (1:1) within each stratum to receive either oral dasatinib 140 mg once daily or 70 mg twice daily. RESULTS: In patients with MBP-CML, the major hematologic response rate was 28% for both regimens; and, in patients with LBP-CML, the major hematologic response rate was 42% for once-daily dasatinib and 32% for twice-daily dasatinib. The major cytogenetic response rates were 25% for once-daily dasatinib and 28% for twice-daily dasatinib in patients with MBP-CML, and the respective rates in patients with LBP-CML were 50% and 40%. The overall survival rate at 24 months was 24% for once-daily dasatinib and 28% for twice-daily dasatinib in patients with MBP-CML, and the respective values in patients with LBP-CML were 21% and 16%. Adverse events indicated a trend toward improved tolerability for the once-daily regimen. CONCLUSIONS: The current results suggested that dasatinib 140 mg once daily had similar efficacy and improved tolerability relative to the 70-mg twice-daily regimen in patients with imatinib-resistant, blast phase CML.

KW - Blast crisis

KW - Chronic myeloid leukemia

KW - Dasatinib

KW - Drug resistance

KW - Imatinib

UR - http://www.scopus.com/inward/record.url?scp=77956823937&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77956823937&partnerID=8YFLogxK

U2 - 10.1002/cncr.25123

DO - 10.1002/cncr.25123

M3 - Article

C2 - 20564086

AN - SCOPUS:77956823937

VL - 116

SP - 3852

EP - 3861

JO - Cancer

JF - Cancer

SN - 0008-543X

IS - 16

ER -