Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
J Clin Oncol. 2010 Mar 20;28(9):1554-9. doi: 10.1200/JCO.2009.26.5785. Epub 2010 Feb 22.
Imatinib plasma trough levels (C(min)) have been reported to correlate with treatment outcomes in patients with gastrointestinal stromal tumors (GISTs). We therefore have evaluated the correlation between imatinib C(min) and the clinical characteristics of patients with GIST.
Steady-state imatinib C(min) in 107 patients with GIST who were taking imatinib 300 to 800 mg/d was measured.
In patients treated with imatinib 400 (n = 92), 300 (n = 7), 600 (n = 2), or 800 (n = 11) mg/d, imatinib C(min) was 1,305 +/- 633 ng/mL, 1,452 +/- 830 ng/mL, 1,698 +/- 725 ng/mL, and 3,330 +/- 1,592 ng/mL, respectively. Of the 92 patients treated with 400 mg/d imatinib, 59 patients (63%) were men; the median age was 55 years (range, 28 to 76 years), and the median duration of imatinib use before sampling was 8.8 months (range, 0.5 to 67.6 months). The mean inter- and intrapatient variability rates were 44.7% and 26.5%, respectively. In univariate analyses, high C(min) was correlated with advanced age (P = .02), low creatinine clearance (P = .001), low hemoglobin (P = .03), and low albumin (P < .001) concentrations. Imatinib C(min) was also significantly lower in patients with (n = 18; 942 +/- 330 ng/mL) than without (n = 74; 1,393 +/- 659 ng/mL) major (ie, total or subtotal) gastrectomy (P = .002). In multivariate analysis, albumin (P = .001) concentrations, creatinine clearance (P = .002), and major gastrectomy (P = .003) were significantly correlated with C(min).
In patients with GIST, imatinib C(min) at steady state was significantly associated with albumin concentration, creatinine clearance, and previous major gastrectomy. Although its clinical impact is unclear at present time, monitoring of imatinib C(min) might be particularly important for optimal treatment with imatinib in patients who have undergone major gastrectomy.
已有报道称，胃肠道间质肿瘤（GIST）患者的伊马替尼血药谷浓度（C（min））与治疗结果相关。因此，我们评估了 GIST 患者的伊马替尼 C（min）与临床特征之间的相关性。
对 107 例服用 300 至 800mg/d 伊马替尼的 GIST 患者的稳态伊马替尼 C（min）进行了测量。
在接受 400mg/d 伊马替尼治疗的 92 例患者（n=92）、300mg/d 伊马替尼治疗的 7 例患者（n=7）、600mg/d 伊马替尼治疗的 2 例患者（n=2）和 800mg/d 伊马替尼治疗的 11 例患者中，伊马替尼 C（min）分别为 1305±633ng/ml、1452±830ng/ml、1698±725ng/ml 和 3330±1592ng/ml。在接受 400mg/d 伊马替尼治疗的 92 例患者中，59 例（63%）为男性；中位年龄为 55 岁（范围 28 至 76 岁），采样前伊马替尼使用的中位时间为 8.8 个月（范围 0.5 至 67.6 个月）。个体内和个体间的变异率分别为 44.7%和 26.5%。单因素分析显示，高 C（min）与高龄（P=0.02）、低肌酐清除率（P=0.001）、低血红蛋白（P=0.03）和低白蛋白（P<0.001）浓度相关。与未行（n=74）相比，行（n=18）主要（即全胃或大部分胃）胃切除术的患者的伊马替尼 C（min）显著更低（P=0.002）。多因素分析显示，白蛋白（P=0.001）浓度、肌酐清除率（P=0.002）和主要胃切除术（P=0.003）与 C（min）显著相关。
在 GIST 患者中，伊马替尼 C（min）在稳态时与白蛋白浓度、肌酐清除率和既往行主要胃切除术显著相关。尽管目前其临床影响尚不清楚，但对于接受主要胃切除术的患者，监测伊马替尼 C（min）可能对伊马替尼的最佳治疗特别重要。
