Dasatinib or high-dose imatinib for chronic-phase chronic myeloid leukemia after failure of first-line imatinib: A randomized phase 2 trial

Hagop Kantarjian, Ricardo Pasquini, Nelson Hamerschlak, Philippe Rousselot, Jerzy Holowiecki, Saengsuree Jootar, Tadeusz Robak, Nina Khoroshko, Tamas Masszi, Aleksander Skotnicki, Andrzej Hellmann, Andrey Zaritsky, Anatoly Golenkov, Jerald Radich, Timothy Hughes, Athena Countouriotis, Neil Shah

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325 Citations (Scopus)


Therapeutic options for chronic myelogenous leukemia (CML) resistant to 400 to 600 mg imatinib are limited. Escalating imatinib doses may overcome resistance. Dasatinib, a significantly more potent inhibitor of BCR-ABL, is safe and effective in this population. Patients with imatinib-resistant chronic-phase (CP) CML were randomized 2:1 to 140 mg dasatinib (n = 101) or 800 mg imatinib (n = 49). With a median follow up of 15 months, complete hematologic responses were observed in 93% and 82% of patients receiving dasatinib and high-dose imatinib (P = .034), respectively. Dasatinib resulted in higher major cytogenetic response rates (52%) than high-dose imatinib (33%) (P = .023); this included complete cytogenetic response in 40% and 16% (P = .004). Major molecular responses were also more frequent with dasatinib (16% versus 4%; P = 0.038). Treatment failure (hazard ratio [HR], 0.16; P < .001) and progression-free survival (HR, 0.14;P <.001) both favored dasatinib. Superficial edema (42% versus 15%) and fluid retention (45% versus 30%) were more prevalent with imatinib; pleural effusion was more common with dasatinib (17% versus 0%). Grade 3 to 4 nonhematologic toxicity was minimal. Cytopenias were more frequent and severe with dasatinib. Dasatinib represents a safe and effective therapy for CP-CML resistant to conventional imatinib doses with improved cytogenetic and molecular response rates and progression-free survival relative to high-dose imatinib.

Original languageEnglish
Pages (from-to)5143-5150
Number of pages8
Issue number12
Publication statusPublished or Issued - 15 Jun 2007

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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