Correlations between imatinib plasma trough concentration and adverse reactions in Chinese patients with gastrointestinal stromal tumors.

Background: Imatinib is the standard treatment for patients with gastrointestinal stromal tumors (GISTs), but there is significant variation in imatinib plasma trough concentrations (C ) among patients. The imatinib C distribution at different doses and the correlation of adverse reactions with C in Chinese patients with GIST from a high-volume center were evaluated.

Methods: From July 1, 2017 to December 31, 2018, patients who were receiving imatinib treatment for GIST were prospectively enrolled. Steady-state blood samples were obtained from patients who had received same-dose imatinib treatment for ≥1 month with good compliance. Adverse reactions were recorded during regular follow-up, and blood samples were collected 24 ± 2 hours after dosing. Liquid chromatography-tandem mass spectrometry was used to measure drug concentrations.

Results: In total, 307 patients who received 367 dose levels were investigated. The imatinib C was 1315 ± 716 ng/mL, 2117 ± 597 ng/mL, and 3844 ± 987 ng/mL in patients who were receiving imatinib 400 mg, 600 mg, and 800 mg daily, respectively. The C was significantly correlated with periorbital and limb edema (P < .001), anemia (P < .001), and rash (P = .037). Nausea and vomiting, diarrhea, and conjunctival hemorrhage also were correlated, but not significantly. A much higher C was observed with severe adverse reactions. There was no correlation between the imatinib C and leukopenia, muscle cramps, or hepatobiliary dysfunction.

Conclusions: In Chinese patients with GIST, the imatinib C was higher than that reported for Western populations, especially at higher doses. The C was correlated with periorbital and limb edema, anemia, and rash, suggesting that monitoring the imatinib C should be considered when patients develop severe adverse reactions caused by excessive imatinib plasma concentrations.