State Key Laboratory of Oncology in South China and Department of Medical Oncology, Cancer Centre, Sun Yat-Sen University, 651 Dong Feng Road East, Guangzhou, 510060, People's Republic of China.
Med Oncol. 2011 Sep;28(3):697-702. doi: 10.1007/s12032-010-9541-0. Epub 2010 May 11.
The objective of this study was to explore the relationship between gefitinib exposure and clinical outcome in gefitinib-treated patients with advanced non-small cell lung cancer. Thirty patients participated in this pharmacokinetic study and received 250-mg oral doses of gefitinib once daily. Blood samples were collected before dosing and on days 7, 14, 21, and 28. The plasma concentrations of gefitinib were evaluated using a validated high-performance liquid chromatographic method with tandem mass spectrometric detection. Univariate and multivariate analyses were performed to determine predictive factors for response and survival of patients. EGFR mutations were analyzed retrospectively. Median survival time (MST) was 9.97 months (95%CI 2.79-17.14 months). The geometric mean trough gefitinib plasma concentration (Cminss was 266 ng/ml (range 94-538 ng/ml). In the multivariate analysis, only skin rash was associated with gefitinib-induced disease control (P=0.017); Adenocarcinoma, skin rash, and 'high' Cminss (Cminss≥200 ng/ml) were independently associated with overall survival (P=0.004, 0.028,0.007, respectively). MST of EGFR wild-type patients with 'high' Cminsswas longer than that with 'low' Cminss (P=0.002). Our study results show that pharmacokinetic variability may also account for the different outcomes following treatment with gefitinib for patients with wild-type EGFR. Further studies are needed to confirm these results.
本研究旨在探讨吉非替尼暴露与接受吉非替尼治疗的晚期非小细胞肺癌患者临床结局的关系。30 名患者参与了这项药代动力学研究，每日接受 250mg 吉非替尼口服剂量。在给药前和第 7、14、21 和 28 天采集血样。使用经过验证的高效液相色谱-串联质谱检测法评估吉非替尼的血浆浓度。进行单变量和多变量分析，以确定患者反应和生存的预测因素。回顾性分析 EGFR 突变。中位生存时间（MST）为 9.97 个月（95%CI 2.79-17.14 个月）。吉非替尼的几何平均谷浓度（Cminss）为 266ng/ml（范围 94-538ng/ml）。多变量分析中，仅皮疹与吉非替尼诱导的疾病控制相关（P=0.017）；腺癌、皮疹和“高”Cminss（Cminss≥200ng/ml）与总生存期独立相关（P=0.004、0.028、0.007）。EGFR 野生型患者中“高”Cminss 的 MST 长于“低”Cminss（P=0.002）。我们的研究结果表明，药代动力学的变异性也可能解释了 EGFR 野生型患者接受吉非替尼治疗后的不同结局。需要进一步的研究来证实这些结果。
