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Blood, 15 April 2008, Vol. 111, No. 8, pp. 4022-4028. Prepublished online as a Blood First Edition Paper on February 6, 2008; DOI 10.1182/blood-2007-10-116475. This Article Full Text Full Text (PDF) Supplemental Appendix All Versions of this Article: blood-2007-10-116475v1 111/8/4022    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Google Scholar Articles by Larson, R. A. Articles by Wang, Y. PubMed PubMed Citation Articles by Larson, R. A. Articles by Wang, Y. Related Collections Neoplasia Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL TRIALS AND OBSERVATIONS Imatinib pharmacokinetics and its correlation with response and safety in chronic-phase chronic myeloid leukemia: a subanalysis of the IRIS study Richard A. Larson1, Brian J. Druker2, Francois Guilhot3, Stephen G. O'Brien4, Gilles J. Riviere5, Tillmann Krahnke6, Insa Gathmann6, Yanfeng Wang7, for the IRIS (International Randomized Interferon vs STI571) Study Group 1 University of Chicago, IL; 2 Oregon Health and Science University Cancer Institute, Portland; 3 Clinical Investigational Center Inserm, Centre Hospitalier Universitaire (CHU), Poitiers, France; 4 University of Newcastle, Newcastle, United Kingdom; 5 Novartis Pharma, Rueil-Malmaison, France; 6 Novartis Pharma, Basel, Switzerland; and 7 Novartis Pharmaceuticals, East Hanover, NJ Imatinib at 400 mg daily is standard treatment for chronic myeloid leukemia in chronic phase. We here describe the correlation of imatinib trough plasma concentrations (Cmins) with clinical responses, event-free survival (EFS), and adverse events (AEs). Trough level plasma samples were obtained on day 29 (steady state, n = 351). Plasma concentrations of imatinib and its metabolite CGP74588 were determined by liquid chromatography/mass spectrometry. The overall mean (± SD, CV%) steady-state Cmin for imatinib and CGP74588 were 979 ng/mL (± 530 ng/mL, 54.1%) and 242 ng/mL (± 106 ng/mL, 43.6%), respectively. Cumulative estimated complete cytogenetic response (CCyR) and major molecular response (MMR) rates differed among the quartiles of imatinib trough levels (P = .01 for CCyR, P = .02 for MMR). Cmin of imatinib was significantly higher in patients who achieved CCyR (1009 ± 544 ng/mL vs 812 ± 409 ng/mL, P = .01). Patients with high imatinib exposure had better rates of CCyR and MMR and EFS. An exploratory analysis demonstrated that imatinib trough levels were predictive of higher CCyR independently of Sokal risk group. AE rates were similar among the imatinib quartile categories except fluid retention, rash, myalgia, and anemia, which were more common at higher imatinib concentrations. These results suggest that an adequate plasma concentration of imatinib is important for a good clinical response. This study is registered at http://clinicaltrials.gov as NCT00333840 [ClinicalTrials.gov] . CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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