Adherence to the standard dose of imatinib, rather than dose adjustment based on its plasma concentration, is critical to achieve a deep molecular response in patients with chronic myeloid leukemia

Int J Hematol. 2011 May;93(5):618-623. doi: 10.1007/s12185-011-0838-3. Epub 2011 Apr 22.

Abstract

The correlation between imatinib (IM) trough plasma concentration (Cmin) and clinical response was assessed in patients with chronic-phase chronic myeloid leukemia. The Cmin correlated with neither the achievement of complete cytogenetic response (977 vs. 993 ng/ml, P = 0.48) nor a major molecular response (1,044 vs. 818 ng/ml, P = 0.17). Although this was significantly higher in patients with complete molecular response (CMR) than in those without (1,430 vs. 859 ng/ml, P = 0.04), the difference was not significant in the sub-population treated with a standard dose of IM (400 mg/day). Finally, multivariate analysis showed that the IM standard dose, but not Cmin, was predictive of the achievement of CMR. We thus suggest that, in practical clinics at least, adherence to the standard dose is the most important factor for the achievement of CMR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Benzamides
  • Cross-Sectional Studies
  • Cytogenetic Analysis
  • Dose-Response Relationship, Drug
  • Drug Dosage Calculations
  • Female
  • Fusion Proteins, bcr-abl / antagonists & inhibitors*
  • Fusion Proteins, bcr-abl / blood
  • Fusion Proteins, bcr-abl / genetics
  • Humans
  • Imatinib Mesylate
  • In Situ Hybridization, Fluorescence
  • Japan
  • Leukemia, Myeloid, Chronic-Phase / blood*
  • Leukemia, Myeloid, Chronic-Phase / drug therapy*
  • Leukemia, Myeloid, Chronic-Phase / pathology
  • Male
  • Middle Aged
  • Piperazines / administration & dosage
  • Piperazines / pharmacokinetics*
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / pharmacokinetics*
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Protein-Tyrosine Kinases / blood
  • Protein-Tyrosine Kinases / genetics
  • Pyrimidines / administration & dosage
  • Pyrimidines / pharmacokinetics*
  • Remission Induction / methods
  • Retrospective Studies
  • Treatment Outcome

Substances

  • Benzamides
  • Piperazines
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Imatinib Mesylate
  • Protein-Tyrosine Kinases
  • Fusion Proteins, bcr-abl