Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2009 Feb 1;115(3):551-60.
doi: 10.1002/cncr.24066.

Efficacy of imatinib dose escalation in patients with chronic myeloid leukemia in chronic phase

Hagop M Kantarjian  1 , Richard A Larson, Francois Guilhot, Stephen G O'Brien, Manisha Mone, Marc Rudoltz, Tillmann Krahnke, Jorge Cortes, Brian J Druker; International Randomized Study of Interferon and STI571 (IRIS) Investigators
Collaborators, Affiliations

Efficacy of imatinib dose escalation in patients with chronic myeloid leukemia in chronic phase

Hagop M Kantarjian et al. Cancer. .

Erratum in

  • Cancer. 2010 Aug 1;116(15):3750. Santini, Valeria [added]

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.

Trial registration: ClinicalTrials.gov NCT00006343.

PubMed Disclaimer

Figures

FIGURE 1
FIGURE 1
Progression-free survival (PFS) (accelerated phase, or blast phase, or death related to chronic myeloid leukemia) for pooled cohorts of dose-escalated patients according to the International Randomized Study of Interferon and STI571 (IRIS) protocol, the European LeukemiaNet (ELN) recommendations, and for the entire patient population. Three patients were not included in the PFS analysis because they had disease progression before dose escalation.
FIGURE 2
FIGURE 2
Overall survival for pooled cohorts of dose-escalated patients according to the International Randomized Study of Interferon and STI571 (IRIS) protocol, the European LeukemiaNet (ELN) recommendations, and for the entire patient population.
See this image and copyright information in PMC

References

    1. Druker BJ, Guilhot F, O’Brien SG, et al. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med. 2007;355:2408–2417. - PubMed
    1. Hochhaus A, Druker BJ, Larson RA, et al. IRIS 6-year follow-up: sustained survival and declining annual rate of transformation in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) treated with imatinib [abstract] Blood. 2007;110 Abstract 25.
    1. Kantarjian HM, Talpaz M, O’Brien S, et al. Dose escalation of imatinib mesylate can overcome resistance to standard-dose therapy in patients with chronic myelogenous leukemia. Blood. 2003;101:473–475. - PubMed
    1. O’Brien SG, Guilhot F, Larson RA, et al. Imatinib compared with interferon and low dose cytarabine for newly diagnosed chronic phase chronic myeloid leukemia. N Engl J Med. 2003;348:994–1004. - PubMed
    1. Baccarani M, Saglio G, Goldman J, et al. Evolving concepts in the management of chronic myeloid leukemia Recommendations from an expert panel on behalf of the European LeukemiaNet. Blood. 2006;6:1809–1820. - PubMed

Publication types

MeSH terms

Associated data