Correlation of imatinib plasma trough concentrations with adverse reaction in Chinese gastrointestinal stromal tumors patients.

11034 Background: Imatinib is the standard treatment for patients of Gastrointestinal Stromal Tumors (GISTs), but the intra- and inter-variability of imatinib plasma trough concentration (Cmin) are significant. Few studies investigated the association between Cmin and adverse reaction in Chinese GIST patients. The distribution of imatinib Cmin in different doses and the correlation of imatinib Cmin with adverse reaction in Chinese GIST patients from a high-volume center were evaluated. Methods: From 1 Jul 2017 to 31 Dec 2018, a total of 400 patients who were under imatinib treatment were prospectively studied. All patients’ informed consents were obtained. Steady state plasma samples were obtained from patients at least administrating 1 month treatment who were taking imatinib 100 to 800 mg/d, with continuous similar timing of daily dosage for more than 14 days. The adverse reaction was recorded during regular follow-up at out-patient clinic, and blood sample was collected 22±2 hours to the next dosage of imatinib. Liquid chromatography tandem mass spectrometry was applied to determine the concentration. Adverse reaction grades were referred to CTCAE v4.0. Results: A total of 368 patients who followed the same dose of imatinib with good compliance, and having at least 2 times of tests were investigated. The imatinib Cmin was 384±53 ng/mL, 776±337 ng/mL, 986±327 ng/mL, 1078±498 ng/mL, 1309±712 ng/mL, 1620±469 ng/mL, 2117±597 ng/mL and 3844±987 ng/mL in patients who were administrated with 100 mg/d (n = 3), 200 mg/d (n = 15), 250 mg/d (n = 5), 300 mg/d (n = 80), 400 mg/d (n = 235), 500 mg/d (n = 3), 600 mg/d (n = 22) and 800 mg/d (n = 5), respectively. In correlation analysis, imatinib Cmin was significantly correlated with periorbital and limbs edema (p < 0.01), anemia (p < 0.01) and rush (p < 0.01), correlated with diarrhea and conjunctival hemorrhage but not significant. Much higher Cmin was observed in severe adverse reaction (≥ grade 3) of periorbital and limbs edema and rash. There was no correlation between Cmin with leukopenia, nausea, vomiting, muscle cramp or hepatobiliary disorders. Conclusions: In Chinese GIST patients, imatinib Cmin at steady state was seems higher than Western populations previous reported, especially in higher doses (≥600 mg/d). Imatinib Cmin was correlated with anemia, periorbital and limbs edema, diarrhea and conjunctival hemorrhage, suggesting that imatinib Cmin monitor might be considered when patients were subjected to severe adverse reactions which were caused by excessive imatinib plasma concentration.