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Efficacy of imatinib dose escalation in patients with chronic myeloid leukemia in chronic phase
Authors:Hagop M. Kantarjian MD  Richard A. Larson MD  Francois Guilhot MD  Stephen G. O'Brien MD  PhD  Manisha Mone  Marc Rudoltz MD  Tillmann Krahnke PhD  Jorge Cortes MD  Brian J. Druker MD
Affiliation:1. Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas;2. Fax: (713) 792‐2031;3. Department of Medicine Hematology/Oncology, University of Chicago, Chicago, Illinois;4. Department of Oncology, Hematology and Cell Therapy, La Milétri University Hospital Center, Poitiers, France;5. Department of Hematology, University of Newcastle, Newcastle, United Kingdom;6. Novartis Pharmaceuticals Corporation, East Hanover, New Jersey;7. Novartis Pharma AG, Basel, Switzerland;8. Department of Hematologic Malignancies, Oregon Health and Science University Cancer Institute, Portland, Oregon
Abstract:

BACKGROUND:

Imatinib mesylate given orally at a daily dose of 400 mg is the standard of care as initial therapy for patients with chronic myeloid leukemia (CML) in chronic phase (CML‐CP). Treatment guidelines propose dose escalation based on clinical assessments of disease response.

METHODS:

Response and survival were analyzed in a cohort of patients (n = 106) with newly diagnosed CML‐CP who were enrolled on the International Randomized Study of Interferon and STI571 (IRIS) trial, who began treatment with imatinib at a dose of 400 mg daily, and who subsequently underwent dose escalation to either 600 mg or 800 mg daily. Reasons for dose escalation were evaluated retrospectively based on 2 sets of criteria: the IRIS protocol‐defined criteria (n = 39 patients) and the European LeukemiaNet (ELN) recommendations (n = 48 patients).

RESULTS:

Among all 106 patients who underwent dose escalation, the rates of freedom from progression to accelerated phase or blast phase and overall survival were 89% and 84% at 3 years after dose increase, respectively. A cytogenetic response was obtained in 42% of patients who had their dose escalated based on protocol criteria and in 38% of patients who had their dose escalated according to the ELN recommendations.

CONCLUSIONS:

The results from this retrospective analysis supported imatinib dose escalation as an appropriate initial option for patients with CML‐CP who were experiencing suboptimal cytogenetic response or resistance. Cancer 2009. © 2008 American Cancer Society.
Keywords:chronic myeloid leukemia in chronic phase  imatinib  dose escalation  suboptimal response
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