Zhang Menghua, Chen Zhiyao, Liu Xiaoxue, Zhou Xiaojun, Miao Liyan
Department of Pharmacy, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
Front Pharmacol. 2025 May 19;16:1604619. doi: 10.3389/fphar.2025.1604619. eCollection 2025.
The imatinib (IMA) steady-state trough concentration (C) plays a critical role in the treatment outcomes of patients with gastrointestinal stromal tumors (GISTs), yet the effective concentration range in the Chinese population remains unclear. Additionally, few studies have investigated the effects of N-desmethyl imatinib (NDI) and genetic polymorphisms in metabolic enzymes and transporters on GIST treatment efficacy. Therefore, the aim of this study was to determine the value of the IMA and total (IMA + NDI) C for the prediction of treatment outcomes in advanced GIST patients and to assess the influence of genetic polymorphisms on the IMA and total (IMA + NDI) C and treatment efficacy. Twenty-one IMA-treated patients with advanced GIST were enrolled. An IMA C ≥950 ng/mL and an IMA + NDI C ≥956 ng/mL were associated with a reduced PD risk, with area under the receiver operating characteristic curve (AUC) values of 0.944 and 0.967, respectively. Higher IMA and IMA + NDI C and higher risks of PD were observed in C allele carriers of rs2231137 and A allele carriers of rs2725252 in and in G allele carriers of rs2631372 in In conclusion, the IMA and IMA + NDI C can serve as effective indicators of advanced GIST treatment outcomes. Drug efficacy should be monitored in patients with an IMA C <950 ng/mL or a total (IMA + NDI) C <956 ng/mL. Furthermore, genetic polymorphism testing is recommended before dosing to appropriately adjust the IMA dose for carriers of the C allele in rs2231137, the A allele in rs2725252 in 2, and the G allele in rs2631372 in .
伊马替尼（IMA）稳态谷浓度（C）在胃肠道间质瘤（GIST）患者的治疗结果中起着关键作用，但中国人群中的有效浓度范围仍不清楚。此外，很少有研究调查N-去甲基伊马替尼（NDI）以及代谢酶和转运体的基因多态性对GIST治疗效果的影响。因此，本研究的目的是确定IMA和总（IMA + NDI）C值对晚期GIST患者治疗结果预测的价值，并评估基因多态性对IMA和总（IMA + NDI）C以及治疗效果的影响。纳入了21例接受IMA治疗的晚期GIST患者。IMA C≥950 ng/mL和IMA + NDI C≥956 ng/mL与降低的疾病进展（PD）风险相关，受试者工作特征曲线（AUC）值分别为0.944和0.967。在rs2231137的C等位基因携带者、rs2725252的A等位基因携带者以及rs2631372的G等位基因携带者中观察到较高的IMA和IMA + NDI C以及较高的PD风险。总之，IMA和IMA + NDI C可作为晚期GIST治疗结果的有效指标。对于IMA C <950 ng/mL或总（IMA + NDI）C <956 ng/mL的患者，应监测药物疗效。此外，建议在给药前进行基因多态性检测，以便为rs2231137的C等位基因携带者、rs2725252的A等位基因携带者以及rs2631372的G等位基因携带者适当调整IMA剂量。
