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Prepublished online as a Blood First Edition Paper on September 12, 2002; DOI 10.1182/blood-2002-05-1451.
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Blood, 15 January 2003, Vol. 101, No. 2, pp. 473-475
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Brief report
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 Faderl,
Deborah Thomas,
Jianqin Shan,
Mary Beth Rios, and
Jorge Cortes
From the Departments of Leukemia and Bioimmunotherapy,
University of Texas M. D. Anderson Cancer Center, Houston, TX.
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.
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Transient benefit only from increasing the imatinib dose in CML patients who do not achieve complete cytogenetic remissions on conventional doses
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Blood 2003 102: 2702-2703.
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