Phase I/II Trial of Cetuximab and Erlotinib in Patients with Lung Adenocarcinoma and Acquired Resistance to Erlotinib
Phase I/II Trial of Cetuximab and Erlotinib in Patients with Lung Adenocarcinoma and Acquired Resistance to Erlotinib
复制标题
DOI：
10.1158/1078-0432.ccr-10-2662
复制
发表时间：
2011-04-15
影响因子：
11.5
通讯作者：
Riely, Gregory J.
中科院分区：
文献类型：
--
作者：
Janjigian, Yelena Y.;Azzoli, Christopher G.;Riely, Gregory J.
目的：对于表皮生长因子受体 (EGFR) 突变型肺腺癌患者，厄洛替尼或吉非替尼治疗的放射学缓解率为 75%，无进展生存期约为 12 个月。厄洛替尼获得性耐药的最常见机制是 EGFR 发生二次突变，表明这些肿瘤继续依赖于 EGFR 信号传导。我们假设联合 EGFR 阻断将克服肺腺癌患者对厄洛替尼的获得性耐药。为了评估西妥昔单抗和厄洛替尼对厄洛替尼获得性耐药患者的毒性和疗效，我们进行了这项 I/II 期临床试验。 实验设计：肺腺癌和临床定义的厄洛替尼获得性耐药患者每天接受厄洛替尼 100 mg 治疗，同时每 2 周服用一次西妥昔单抗，分为三个剂量递增组（250 mg/m(2)、375毫克/米 (2) 和 500 毫克/米 (2)）。然后在两阶段试验中评估推荐的 II 期剂量，主要终点为客观缓解率。结果：共有 19 名患者入组。西妥昔单抗和厄洛替尼组合最常见的毒性是皮疹、疲劳和低镁血症。确定的推荐 II 期剂量为西妥昔单抗 500 mg/m 2 每两周一次，厄洛替尼每日 100 mg。在此剂量和时间表下，未观察到放射学反应（13 中的 0 例，0%，95% CI，0-25）。 结论：每 2 周使用西妥昔单抗 500 mg/m(2) 和每日 100 mg 厄洛替尼联合 EGFR 抑制，对厄洛替尼获得性耐药的患者没有显着活性。临床癌症研究； 17(8)； 2521-7。 (C) 2011 年 AACR。
Purpose: In patients with epidermal growth factor receptor (EGFR) mutant lung adenocarcinoma, treatment with erlotinib or gefitinib is associated with a 75% radiographic response rate and progression-free survival of approximately 12 months. The most common mechanism of acquired resistance to erlotinib is development of a secondary mutation in EGFR, suggesting that these tumors continue to depend on EGFR signaling. We hypothesized that combined EGFR blockade would overcome acquired resistance to erlotinib in patients with lung adenocarcinoma. To evaluate the toxicity and efficacy of cetuximab and erlotinib in patients with acquired resistance to erlotinib, we conducted this phase I/II clinical trial.Experimental Design: Patients with lung adenocarcinoma and clinically defined acquired resistance to erlotinib were treated with erlotinib 100 mg daily, along with cetuximab every 2 weeks in three escalating dose cohorts (250 mg/m(2), 375 mg/m(2), and 500 mg/m(2)). The recommended phase II dose was then evaluated in a two-stage trial, with a primary end point of objective response rate.Results: A total of 19 patients were enrolled. The most common toxicities for the combination of cetuximab and erlotinib were rash, fatigue, and hypomagnesemia. The recommended phase II dose identified was cetuximab 500 mg/ m 2 every 2 weeks and erlotinib 100 mg daily. At this dose and schedule, no radiographic responses were seen (0 of 13, 0%, 95% CI, 0-25).Conclusions: Combined EGFR inhibition, with cetuximab 500 mg/m(2) every 2 weeks and erlotinib 100 mg daily, had no significant activity in patients with acquired resistance to erlotinib. Clin Cancer Res; 17(8); 2521-7. (C) 2011 AACR.