Dose escalation of imatinib mesylate can overcome resistance to standard-dose therapy in patients with chronic myelogenous leukemia

Hagop M. Kantarjian, Moshe Talpaz, Susan O'Brien, Francis Giles, Guillermo Garcia-Manero, Stefan Faded, Deborah Thomas, Jianqin Shan, Mary Beth Rios, Jorge Cortes

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261 Scopus citations

Abstract

We investigated whether increasing the dose of imatinib mesylate might overcome drug resistance in patients with Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML) whose disease manifests relapse or refractoriness to therapy. Fifty-four patients with Ph+ CML in chronic phase and with hematologic or cytogenetic resistance or relapse on imatinib mesylate therapy at 400 mg orally daily were treated with a higher dose of 400 mg orally twice daily (800 mg daily, 47 patients; or 600 mg daily increased from 300 mg daily, 7 patients). Among 20 patients treated for hematologic resistance or relapse, 13 (65%) achieved a complete (n = 9) or partial (n = 4) hematologic response, but only 1 had a cytogenetic partial response (Ph reduction from 100% to 10%) and 1 had a minor response (Ph reduction from 100% to 50%). Among 34 patients treated for cytogenetic resistance or relapse, 19 (56%) achieved a complete (n = 6) or partial (n = 7) cytogenetic response. We conclude that higher doses of imatinib mesylate may overcome disease-poor response to conventional doses and that this approach deserves further evaluation as frontline therapy for newly diagnosed CML.

Original languageEnglish (US)
Pages (from-to)473-475
Number of pages3
JournalBlood
Volume101
Issue number2
DOIs
StatePublished - Jan 15 2003
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Kantarjian, H. M., Talpaz, M., O'Brien, S., Giles, F., Garcia-Manero, G., Faded, S., Thomas, D., Shan, J., Rios, M. B., & Cortes, J. (2003). Dose escalation of imatinib mesylate can overcome resistance to standard-dose therapy in patients with chronic myelogenous leukemia. Blood, 101(2), 473-475. https://doi.org/10.1182/blood-2002-05-1451