Phase II prospective study of the efficacy of gefitinib for the treatment of stage III/IV non-small cell lung cancer with EGFR mutations, irrespective of previous chemotherapy
Phase II prospective study of the efficacy of gefitinib for the treatment of stage III/IV non-small cell lung cancer with EGFR mutations, irrespective of previous chemotherapy
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DOI：
10.1016/j.lungcan.2007.01.025
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发表时间：
2007-06-01
期刊：
影响因子：
5.3
通讯作者：
Mori, Masatomo
中科院分区：
文献类型：
--
作者：
Sunaga, Noriaki;Tomizawa, Yoshio;Mori, Masatomo
目的：表皮生长因子受体（EGFR）基因突变与非小细胞肺癌敏感性增加相关。细胞肺癌（NSCLC）的吉非替尼，EGFR酪氨酸激酶抑制剂。本研究的目的是前瞻性地评估吉非替尼在III/IV期NSCLC患者的疗效，其肿瘤携带EGFR突变，无论以前chemotherapy.Experimental design：基因组DNA提取肿瘤标本和EGFR突变外显子19和21直接测序分析。肿瘤有EGFR突变的III/IV期NSCLC患者接受吉非替尼（250 mg/天口服）。结果：从2004年11月至2006年5月，21例EGFR突变患者接受吉非替尼（中位年龄：59岁; 17名女性; 19名非吸烟者;所有腺癌）。2例患者停用吉非替尼，并在吉非替尼治疗开始后3周退出研究（间质性肺炎，1例患者;面部痤疮，1例患者）。19例患者中，3例完全缓解，13例部分缓解，3例病情稳定。缓解率和疾病控制率分别为76%（95%置信区间[CI] 53-92）和90%（95% CI 70-99）。最常见的不良事件是皮肤毒性（67%）;然而，没有观察到4级皮肤毒性。10例患者复发，3例死亡，中位随访期为12.6个月（范围5.6-23.8个月），中位无进展生存期为12.9个月。结论：分析肿瘤EGFR突变的NSCLC患者，可用于确定适合与吉非替尼治疗的患者，以获得最佳的反应和疾病控制率。(c)2007爱思唯尔爱尔兰有限公司保留所有权利。
Purpose: Mutations in the epidermal growth factor receptor (EGFR) gene are associated with increased sensitivity of non-small. cell Lung cancer (NSCLC) to gefitinib, an EGFR tyrosine kinase inhibitor. The objective of this study was to prospectively evaluate the efficacy of gefitinib in patients with stage III/IV NSCLC whose tumors carried EGFR mutations, irrespective of previous chemotherapy.Experimental design: Genomic DNA was extracted from tumor specimens and EGFR mutations in exons 19 and 21 analyzed by direct sequencing. Patients with stage III/IV NSCLC whose tumors had the EGFR mutations received gefitinib (250 mg/day orally). Response, toxicity and survival data were assessed.Result: From November 2004-May 2006, 21 patients with EGFR mutations received gefitinib (median age: 59 years; 17 females; 19 non-smokers; all had adenocarcinomas). Two patients discontinued gefitinib and withdrew from the study 3 weeks after gefitinib initiation (interstitial pneumonitis, 1 patient; facial acne, 1 patient). Of 19 patients, 3 achieved complete response, 13 exhibited partial response and 3 had stable disease. Response and disease control rates were 76% (95% confidence interval [CI] 53-92) and 90% (95% Cl 70-99), respectively. The most common adverse event was skin toxicity (67%); however, no grade 4 skin toxicities were seen. Ten patients relapsed and three died at a median follow-up period of 12.6 months (range 5.6-23.8 months); median progression-free survival was 12.9 months.Conclusion: Analysis of tumor EGFR mutations in patients with NSCLC could be used to identify patients suitable for treatment with gefitinib to obtain optimum response and disease control rates. (c) 2007 Elsevier Ireland Ltd. All rights reserved.