IMATINIB SERUM LEVELS IN GIST PATIENTS

J Clin Oncol. 2009 May 18. [Epub ahead of print]

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Imatinib Plasma Levels Are Correlated With Clinical Benefit in Patients With Unresectable/Metastatic Gastrointestinal Stromal Tumors.

Demetri GD, Wang Y, Wehrle E, Racine A, Nikolova Z, Blanke CD, Joensuu H, von Mehren M.

Ludwig Center, Dana-Farber/Harvard Cancer Center, and Harvard Medical School, Boston, MA; Oncology Business Unit, Novartis Pharmaceuticals Corp, Florham Park, NJ; Oncology Business Unit and Biostatistics, Novartis Pharmaceuticals AG, Basel, Switzerland; British Columbia Cancer Agency, University of British Columbia, Vancouver, British Columbia, Canada; Department of Oncology, Helsinki University Central Hospital, Helsinki, Finland; and Fox Chase Cancer Center, Philadelphia, PA.

PURPOSE: To study the pharmacokinetics (PK) of imatinib (IM) in patients with advanced GI stromal tumors (GISTs) treated in a randomized phase II study and to explore the potential relationship between IM plasma levels and long-term clinical outcomes. PATIENTS AND METHODS: Patients were randomly assigned to receive IM at 400 mg versus 600 mg daily. IM plasma levels were analyzed in a subset of patients (n = 73) for whom PK data on day 1 and at steady-state (SS, day 29) were available. IM PK was evaluated using a population PK approach. The relationship between IM plasma exposure and clinical outcome was explored by grouping patients into quartiles according to IM trough concentration (Cmin). The clinical outcome parameters evaluated include overall objective benefit rate (OOBR; complete response plus partial response plus stable disease) time to progression (TTP), and KIT genotyping. RESULTS: IM PK exposure showed a high inter-patient variability, and clinical outcomes were correlated with IM trough levels at SS. The median TTP was 11.3 months for patients in the lowest Cmin quartile (Q1, < p =" .0029)." n =" 39)," p =" .001).">