Xia Yanzhe, Chen Sile, Luo Meijuan, Wu Jingjing, Cai Shirong, He Yulong, Chen Xiao, Zhang Xinhua
Department of Pharmacy, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Department of Gastrointestinal Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Cancer. 2020 May 1;126 Suppl 9:2054-2061. doi: 10.1002/cncr.32751.
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.
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.
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.
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.
伊马替尼是胃肠道间质瘤（GIST）患者的标准治疗药物，但患者间伊马替尼血浆谷浓度（C）存在显著差异。本研究评估了中国一家大型中心的GIST患者在不同剂量下伊马替尼C的分布情况以及不良反应与C的相关性。
2017年7月1日至2018年12月31日，前瞻性纳入接受伊马替尼治疗GIST的患者。从接受相同剂量伊马替尼治疗≥1个月且依从性良好的患者中采集稳态血样。在定期随访期间记录不良反应，并在给药后24±2小时采集血样。采用液相色谱 - 串联质谱法测定药物浓度。
共纳入307例接受367个剂量水平治疗的患者。接受伊马替尼每日400mg、600mg和800mg治疗的患者，其伊马替尼C分别为1315±716ng/mL、2117±597ng/mL和3844±987ng/mL。C与眶周及肢体水肿（P <.001）、贫血（P <.001）和皮疹（P =.037）显著相关。恶心呕吐、腹泻和结膜出血也存在相关性，但不显著。严重不良反应患者的C值更高。伊马替尼C与白细胞减少、肌肉痉挛或肝胆功能障碍之间无相关性。
在中国GIST患者中，伊马替尼C高于西方人群报道的水平，尤其是在较高剂量时。C与眶周及肢体水肿、贫血和皮疹相关，提示当患者因伊马替尼血浆浓度过高出现严重不良反应时，应考虑监测伊马替尼C。
