Cytotoxic chemotherapy may overcome the development of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) therapy
Cytotoxic chemotherapy may overcome the development of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) therapy
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DOI：
10.1016/j.lungcan.2015.06.016
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发表时间：
2015-09-01
期刊：
影响因子：
5.3
通讯作者：
Ohe, Yuichiro
中科院分区：
文献类型：
--
作者：
Kanda, Shintaro;Horinouchi, Hidehito;Ohe, Yuichiro
目的：在携带EGFR突变的非小细胞肺癌（NSCLC）的一线治疗中，表皮生长因子受体（EGFR）-酪氨酸激酶抑制剂（TKI）已被证明比铂双联化疗产生更长的无进展生存期（PFS）;然而，在初始缓解后，大多数患者对EGFR-TKI产生耐药性。我们假设，插入铂双联化疗后，对EGFR-TKIs的初步反应可能会防止出现获得性耐药EGFR-TKIs和延长survival.Methods：我们进行了一项II期研究，以下一线治疗晚期NSCLC携带EGFR突变的患者。第1-56天给予吉非替尼（250 mg）。然后，在两周的停药期后，在第71、92和113天给予三个周期的顺铂（80 mg/m2）和多西他赛（60 mg/m2）。此后，在第134天重新开始吉非替尼治疗，并持续至疾病进展。主要终点是两年无进展生存率。结果：共入组34例患者。在33例合格患者中，12例患者实现了2年PFS。因此，该治疗策略符合有效性标准。1、2、3和5年PFS率分别为67.0%、40.2%、36.9%和22.0%，中位PFS为19.5个月。1、2、3、5年生存率分别为90.6%、71.9%、64.8%、36.5%，中位生存期为48.0个月。结论：铂类双药联合化疗可预防EGFR突变的晚期NSCLC患者对EGFR TKI的获得性耐药。(C)2015爱思唯尔爱尔兰有限公司版权所有。
Objectives: In the first-line treatment of non-small cell lung cancer (NSCLC) harboring EGFR mutations, epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) has been shown to yield a longer progression-free survival (PFS) rate than platinum-doublet chemotherapy; however, after the initial response, most patients develop resistance to the EGFR-TKIs. We hypothesized that the insertion of platinum-doublet chemotherapy after the initial response to EGFR-TKIs might prevent the emergence of acquired resistance to EGFR-TKIs and prolong survival.Methods: We carried out a phase II study of the following first-line treatment for patients with advanced NSCLC harboring EGFR mutations. Gefitinib (250 mg) was administered on days 1-56. Then, after a two-week drug-free period, three cycles of cisplatin (80 mg/m(2)) and docetaxel (60 mg/m(2)) were administered on days 71, 92, and 113. Thereafter, gefitinib was re-started on day 134 and continued until disease progression. The primary endpoint was the two-year PFS rate.Results: A total of 34 patients were enrolled. Of the 33 eligible patients and 12 achieved a two-year PFS. Thus, this therapeutic strategy met the criterion for usefulness. The 1-, 2-, 3-, and 5-year PFS rates were 67.0%, 40.2%, 36.9%, and 22.0%, respectively, and the median PFS was 19.5 months. The 1-, 2-, 3- and 5-year survival rates were 90.6%, 71.9%, 64.8%, and 36.5% respectively, and the median survival time was 48.0 months.Conclusion: These results indicate that the insertion of platinum-doublet chemotherapy might prevent the development of acquired resistance to EGFR-TKIs in patients with advanced NSCLC harboring EGFR mutations. (C) 2015 Elsevier Ireland Ltd. All rights reserved.