Trough imatinib plasma levels in patients treated for advanced gastrointestinal stromal tumors evidence of large interpatient variations under treatment with standard doses

Abstract

10564 Background: Large interpatient variations of trough imatinib level have been reported in patients with CML given imatinib 400- 600 mg/d; moreover, the 24h residual plasma level of imatinib was found correlated with imatinib efficacy. Methods: Trough plasma levels of imatinib were determined by high performance liquid chromatography-tandem mass spectrometry in patients with advanced GIST, seen at IB 24h (imatinib 400 mg/d) or 12h (imatinib 400 mg bid) after the last dose intake. Results: From March 2007 to October 2007, 31 dosages were performed in 24 patients. Imatinib dose was 400 mg/d (median duration 26 months), for 24 determinations, and 800 mg/d for 7 (dose increased for tumor progression in 6). There were 11 female and 13 male patients and the median age was 66 years (range: 45–90); treatment was for liver (6), peritoneal 7) metastasis or both (8); 3 patients had inoperable primaries. Mean and median trough plasma levels were 799 and 450ng/ml (range: 188–3,321) for a prescribed dose of 400 mg/d and 1,778 and 715 ng/ml (range 374–3,349) for 800 mg/d. Five patients are still responders for 5 years or more and 4/5 had imatinib levels >1000 ng/ml. The inter-patient variability was in contrast to low intra- patient variability, except in one patient whose compliance was corrected. Among 4 patients with very low levels (3 with <250 ng/ml at 400 mg/d, and 1 at 374 ng/ml at 800 mg/d), poor compliance to treatment could be suspected in 3 patients; 3 of those patients were imatinib responders. In this series, no relationship between imatinib trough plasma levels and drug interaction was found. Conclusions: In this preliminary study, large inter-patient variations of imatinib trough plasma levels were found. Very low levels suggest a bad compliance to treatment. High trough imatinib levels were found in long-term responders to imatinib. It remains to be determined whether a threshold that is correlated with optimal drug efficacy exists. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novartis Novartis