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63例肺癌患者埃克替尼新辅助治疗的回顾性分析。

Retrospective analysis of icotinib neoadjuvant therapy of 63 lung cancer patients.

作者信息

Wang T, Liu Y, Zhou B, Hao S, Wang Z, Liang N, Liu J, Wang S

机构信息

Department of Thoracic Surgery, PLA General Hospital, Beijing 100853, China.

出版信息

Indian J Cancer. 2017 Jan-Mar;54(1):215-222. doi: 10.4103/0019-509X.219585.

Abstract

OBJECTIVE

This study aims to explore the feasibility of icotinib neoadjuvant therapy for nonsmall cell lung cancer (NSCLC).

MATERIALS AND METHODS

This was a retrospective analysis of the clinical data for 63 NSCLC patients (61 cases of adenocarcinoma and two cases of squamous cell carcinoma) receiving surgical resection of lung lesions after oral intake of icotinib from December 2011 to November 2013 in the PLA General Hospital. Preoperative oral intake of the patients was icotinib 125 mg tid, drug side effects were evaluated according to the American National Cancer Institute Common Toxicity Criteria Version 4.0; computed tomography scan was done on the day taking medicine and 2 weeks later to determine tumor changes. After oral intake of Icotinib for 2 to 22 weeks (5 cases for 2 weeks,13 cases for 3 to 22 weeks), all patients receive surgical resection of lung cancer lesions, and testing of removed tumor to evaluate the epidermal growth factor receptor (EGFR) gene mutation status was performed by fluorescence polymerase chain reaction. The patients with sensitive EGFR mutations receive Icotinib as postoperative adjuvant therapy.

RESULTS

Side effects of medication within 2 weeks included rash (44.4%, 28/63), dry skin (34.9%, 22/63), diarrhea (14.3%, 9/63), and oral ulcer (1.6%, 1/63); there were no icotinib-associated thoracic surgery complications during the perioperational period. 71.4% patients (45/63) achieve an average reduction of 23.5% ±10.7%(10%-53.5%) after 2 weeks medication of Icotinib(regressive tumor[RT]) .28.6% patients(18/63) achieve stable tumor(ST),enlargement of 8.7% to reduction of 8.7% of the maximum diameter of lung cancer after 2 weeks medication of Icotinib. Of the RT group, 68.9% (31/45) of the tumors were detected with EGFR-sensitive mutation (exon 19 or 21 mutation), 24.4% (11/45) with wild-type EGFR, and three cases of exon 20 mutation. Of the ST group, 77.8% (14/18) were detected with wild-type EGFR, three cases of exon 20 mutation, and one case of exon 19 deletion mutation (tumor reduction by 7.9%). 45 cases in RT group and 1 case with EGFR 19 exon metation in ST group receive Icotinib as adjuvant therapy. Among 45 cases in RT group and 18 cases in ST group, there was no difference in gender, age, smoking history, tumor diameter, tumor differentiation degree, and incidence of side effects (P = 0.076). There was significant difference (P < 0.0001) in terms of symptom remission rate after medication and EGFR gene-sensitive mutation rate in RT and ST groups.

CONCLUSION

Icotinib neoadjuvant therapy for NSCLC is safe and feasible, and the reactivity of lung cancer patients to icotinib can be determined within 2 weeks of medication. People sensitive to preoperative selection of drugs can more accurately determine the sensitivity of tumors to drugs, thus providing evidence for postoperative adjuvant therapy.

摘要

目的

本研究旨在探讨埃克替尼新辅助治疗非小细胞肺癌(NSCLC)的可行性。

材料与方法

对2011年12月至2013年11月在中国人民解放军总医院口服埃克替尼后接受肺部病变手术切除的63例NSCLC患者(61例腺癌和2例鳞癌)的临床资料进行回顾性分析。患者术前口服埃克替尼125mg,每日3次,根据美国国立癌症研究所通用毒性标准第4.0版评估药物不良反应;服药当日及2周后行计算机断层扫描以确定肿瘤变化。口服埃克替尼2至22周(2周的5例,3至22周的13例)后,所有患者接受肺癌病变手术切除,并通过荧光聚合酶链反应检测切除肿瘤的表皮生长因子受体(EGFR)基因突变状态。EGFR敏感突变患者术后接受埃克替尼辅助治疗。

结果

2周内药物不良反应包括皮疹(44.4%,28/63)、皮肤干燥(34.9%,22/63)、腹泻(14.3%,9/63)和口腔溃疡(1.6%,1/63);围手术期无埃克替尼相关的胸外科手术并发症。71.4%的患者(45/63)在口服埃克替尼2周后平均缩小23.5%±10.7%(10% - 53.5%)(肿瘤退缩[RT])。28.6%的患者(18/63)肿瘤稳定(ST),口服埃克替尼2周后肺癌最大直径增大8.7%至缩小8.7%。在RT组中,68.9%(31/45)的肿瘤检测到EGFR敏感突变(外显子19或21突变),24.4%(11/45)为野生型EGFR,3例为外显子20突变。在ST组中,77.8%(14/18)检测为野生型EGFR,3例为外显子20突变,1例为外显子19缺失突变(肿瘤缩小7.9%)。RT组45例和ST组1例EGFR 19外显子突变患者接受埃克替尼辅助治疗。RT组45例和ST组18例患者在性别、年龄、吸烟史、肿瘤直径、肿瘤分化程度及不良反应发生率方面无差异(P = 0.076)。RT组和ST组服药后症状缓解率及EGFR基因敏感突变率差异有统计学意义(P < 0.0001)。

结论

埃克替尼新辅助治疗NSCLC安全可行,肺癌患者在服药2周内可确定对埃克替尼有无反应。术前筛选出的敏感人群能更准确地判断肿瘤对药物的敏感性,为术后辅助治疗提供依据。

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