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 (Cmin) among patients. The imatinib Cmin distribution at different doses and the correlation of adverse reactions with...

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Bibliographic Details
Published in:Cancer 2020-05, Vol.126 (S9), p.2054-2061
Main Authors: Xia, Yanzhe, Chen, Sile, Luo, Meijuan, Wu, Jingjing, Cai, Shirong, He, Yulong, Chen, Xiao, Zhang, Xinhua
Format: Article
Language:English
Subjects:
adverse reactions
Anemia
Antineoplastic Agents - therapeutic use
Blood
China - epidemiology
Correlation
Cramps
Diarrhea
Dosage
Edema
Exanthema
Exanthema - chemically induced
Exanthema - drug therapy
Gastrointestinal cancer
gastrointestinal stromal tumors
Gastrointestinal Stromal Tumors - drug therapy
Gastrointestinal Stromal Tumors - pathology
Hemorrhage
Humans
Imatinib
Imatinib Mesylate - adverse effects
Leukopenia
Liquid chromatography
Mass spectrometry
Mass spectroscopy
Muscles
Nausea
Oncology
pharmacokinetics
Side effects
Tumors
Vomiting
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Summary:Background Imatinib is the standard treatment for patients with gastrointestinal stromal tumors (GISTs), but there is significant variation in imatinib plasma trough concentrations (Cmin) among patients. The imatinib Cmin distribution at different doses and the correlation of adverse reactions with Cmin 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 Cmin 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 Cmin was significantly correlated with periorbital and limb edema (P 
ISSN:0008-543X
1097-0142
DOI:10.1002/cncr.32751