吉非替尼治疗晚期非小细胞肺癌脑转移的疗效

目的探讨吉非替尼治疗非小细胞肺癌(NSCLC)脑转移的疗效及其对预后的影响。方法44例NSCLC脑转移患者中,接受过全脑放疗者30例,接受过化疗者42例,均在入组前1个月结束治疗。入组者口服吉非替尼250 mg,每日1次,服药至疾病进展或死亡。服药后定期复查。结果吉非替尼治疗的有效率为31.8%,稳定率为47.7%,临床获益率为79.5%。中位无进展生存时间为9个月,中位总生存时间为13个月。吉非替尼对颅内转移灶的控制率达81.9%。既往接受全脑放疗患者与未接受全脑放疗者相比,其转移灶控制率差异无统计学意义(P=0.566)。结论吉非替尼治疗NSCLC脑转移的疗效显著,不良反应轻微,能明显改善患者预后,是晚期NSCLC患者的治疗方法之一。     

厄洛替尼联合全脑放疗治疗NSCLC脑转移的疗效及患者生存分析

目的研究厄洛替尼联合全脑放疗治疗非小细胞肺癌脑转移的疗效以及患者生存效果。方法随机选取非小细胞肺癌患者98例,根据治疗途径分为对照组和实验组,每组49例患者。对照组患者接受全脑放疗;实验组患者接受厄洛替尼联合全脑放疗,即患者在放疗开始应用厄洛替尼片,应用到放疗完成后2个月为止。对全部入组患者定期进行住院或者门诊随访。结果 2组患者经治疗后,实验组患者完全缓解率为12.2%,部分缓解率为28.6%,病灶稳定率为42.9%,病灶进展率为16.3%,而对照组患者完全缓解仅有1例,差异具有统计学意义(χ~2=3.950,P<0.05)。2组对比,对照组患者的疾病控制率远远低于实验组,差异具有统计学意义(χ~2=1.376,P<0.05);此外,实验组患者的生存时间明显长于对照组,差异具有统计学意义(P<0.05)。实验组患者主要的不良反应为皮疹和恶心呕吐。结论厄洛替尼联合全脑放疗治疗非小细胞肺癌脑转移,疗效显著,能够有效地控制脑转移病灶,提高患者客观有效率和生存率。     

SRT联合拉帕替尼治疗HER2阳性乳腺癌脑转移疗效及预后分析

目的 探讨立体定向放射治疗(Stereotactic radiotherapy,SRT)联合拉帕替尼治疗HER2阳性乳腺癌脑转移的疗效及预后。方法 回顾性分析91例HER2阳性乳腺癌脑转移患者接受拉帕替尼靶向治疗的同时接受全脑放疗或SRT的情况,其中42例患者接受SRT的同时进行拉帕替尼联合卡培他滨治疗(SRT组),另外49例患者采用全脑放疗同时进行拉帕替尼联合卡培他滨治疗(全脑放疗组)。评价其疗效和毒性,定期随访,并行多因素Cox回归分析其预后相关因素。结果 放疗结束后1月SRT组脑部病灶客观缓解率为92.86%(39/42),全脑放疗组客观缓解率为77.55%(38/49),SRT组优于全脑放疗组(χ²=4.070,P=0.044)。SRT组和全脑组12个月受照射肿瘤病灶无进展生存率分别为95.20%及83.10%, SRT组优于全脑放疗组(χ²=10.851,P=0.001)。 SRT组无颅内转移生存率与全脑放疗组无统计学差异(P＞0.05)。SRT组和全脑放疗组1年生存率分别为85.70%和69.40%,2年生存率分别为66.70%和55.10%,两组中位生存期分别为31.56个月和25.00个月,SRT组优于全脑放疗组(P=0.002)。多因素Cox回归分析结果表明无颅外转移(HR=0.527,95% CI:0.290~0.957,P=0.035),颅内病灶≤3个(HR=2.457,95% CI:1.223~4.933,P=0.012),放疗方式SRT(HR=1.746,95% CI:1.055~2.888,P=0.030)是HER2阳性乳腺癌脑转移放疗预后的独立保护因素。结论 SRT联合拉帕替尼在局部控制率以及生存率上优于全脑放疗联合拉帕替尼。颅内病灶个数少、无颅外转移灶和放疗方式是HER2阳性乳腺癌脑转移治疗的良好预后因素。     

克唑替尼联合脑转移灶切除、全脑放疗治疗ROS1阳性伴有症状脑转移的肺腺癌1例及文献复习

背景与目的伴有脑转移的肺癌预后差。克唑替尼可有效治疗ROS1（C-ros oncogene 1 receptor tyrosine kinase）融合基因阳性的肺癌,但由于血脑屏障通透率较低,对脑转移灶的治疗效果不佳。本文总结1例综合运用手术、全脑放疗+残留灶补量放疗及克唑替尼等手段治疗ROS1融合基因阳性伴有症状脑转移的肺腺癌患者,并对其有效性及安全性进行讨论和分析。方法采用手术切除占位效应明显、引起头疼症状的颅内病灶,获得病理;因ROS1融合基因阳性,给予克唑替尼治疗,250 mg,2次/d;术后进行全脑放疗+残留灶补量放疗。按照实体瘤疗效评价标准1.1版（Response Evaluation Criteriation in Solid Tumours, RECIST v1.1）评价客观疗效。按照不良反应通用术语标准4.0版（ Common Terminology Criteria for Adverse Events v4.0, CTC AE v4.0）评估用药期间发生的不良事件。结果该患者服用克唑替尼3个月后,肺部病变接近完全缓解（complete remission, CR）,颅内病变部分缓解（partial response, PR）,腹腔病变CR,视物模糊症状减轻。结论综合运用手术、全脑放疗+残留灶补量放疗、克唑替尼治疗ROS1融合基因阳性伴有症状脑转移的肺腺癌患者,可有效控制颅内颅外病灶,耐受性好。     

克唑替尼治疗ALK阳性非小细胞肺癌脑转移的疗效观察

背景与目的：克唑替尼对间变性淋巴瘤激酶(anaplastic lymphoma kinase,ALK)阳性非小细胞肺癌(non-small cell lung cancer,NSCLC)具有显著疗效,但在治疗中往往出现脑转移,本研究旨在探讨克唑替尼在ALK阳性NSCLC脑转移患者中的治疗疗效和治疗模式。方法：对2011年1月—2014年8月在解放军八一医院接受克唑替尼治疗的6例ALK阳性NSCLC脑转移患者的临床资料进行回顾性分析。结果：3例克唑替尼治疗前基线有脑转移患者,颅内疗效部分缓解(partial response,PR)1例、疾病稳定(stable disease,SD)2例;第1次服用克唑替尼治疗至第1次出现疾病进展(progressive disease,PD)的中位时间为5.7个月,且第1次疾病进展的部位均为脑。6例患者脑病灶进展接受放疗后继续服用克唑替尼治疗,中位无进展生存期(progression free survival,PFS)为4.0个月,其中1例患者继续接受克唑替尼治疗的PFS达23.3个月,颅内病灶疗效完全缓解(complete response,CR)。结论：克唑替尼治疗ALK阳性NSCLC脑转移患者有效,且对于单纯颅内病灶进展放疗后,继续接受克唑替尼治疗仍然有效,是临床上可以选择的治疗方式。     

厄洛替尼治疗非小细胞肺癌脑转移初步分析

背景与目的 非小细胞肺癌(Non-small-cell lung cancer,NSCLC)脑转移较常见,预后不佳.厄洛替尼是一种表皮生长因子受体酪氨酸激酶抑制剂,多应用于治疗晚期NSCLC.本研究拟了解厄洛替尼治疗NSCLC脑转移的疗效、预后及其相关因素.方法 回顾性分析30例NSCLC脑转移患者的临床资料,所有患者均口服厄洛替尼150mg/d.直到疾病进展、死亡或发生不可耐受的副反应.结果 厄洛替尼对颅内病灶的疗效为部分缓解2例(6.7%).疾病稳定17例(56.7%).疾病控制率为63.4%,对全身病变的总体疗效为部分缓解2例(6.7%),疾病稳定5例(16.7%),疾病控制率为23.4%.年龄、性别、吸烟状况、病理类型、PS评分、脑转移数目、脑转移时间、化疗及脑部放疗与否、副反应等各亚组之间的疗效对比均未见有统计学差异.中位疾病进展时间2.4个月,中位生存期7.7个月,1年、2年生存率分别为38.4%和15.2%.单因素分析显示生存期与患者的PS评分、吸烟状况、是否进行过脑部放疗及化疔具有相关性,多因素分析则显示生存期仅与患者是否进行过脑部放疗具有相关性,与患者的吸烟状况接近有统计学意义.结论 厄洛替尼对NSCLC脑转移具有一定的疗效,接受过脑部放疗的患者具有较好的生存获益,非吸烟者的生存时间有好于吸烟者的趋势.厄洛替尼可以作为NSCLC脑转移的一种治疗选择.     

厄洛替尼辅助全脑放疗治疗肺癌脑转移的临床疗效

目的探讨厄洛替尼辅助全脑放疗治疗肺癌脑转移的临床效果。方法选取2011年1月至2014年10月间接受治疗的72例肺癌脑转移患者,其中小细胞肺癌32例,腺癌24例,鳞癌16例。所有患者均给予常规支持治疗,如减轻颅内水肿等。在此基础上进行全脑放疗治疗以及厄洛替尼辅助治疗,分析2个月后患者的临床治疗效果。结果 72例患者部分缓解52例,疾病稳定20例,临床获益率为100.0%,临床有效率为72.2%。其中,小细胞肺癌的临床有效率为68.8%,腺癌临床有效率为75.0%,鳞癌临床有效率为75.0%。36例患者治疗后出现皮疹30例(41.7%),腹泻30例(41.7%),乏力64例(88.9%),脱发16例(22.2%),粒细胞降低6例(8.3%)。结论厄洛替尼辅助全脑放疗治疗肺癌脑转移疗效较为显著,可有效改善患者临床症状、延长患者生存期,且安全性较好,在临床上值得推广。     

吉非替尼对EGFR敏感突变肺腺癌脑转移患者的预后影响

摘 要：［目的］ 了解吉非替尼在EGFR敏感突变肺腺癌脑转移患者中的生存情况,进一步分析临床、影像及药物动力学等因素对预后有无影响。［方法］ 37例初治EGFR 敏感突变肺腺癌脑转移患者口服吉非替尼250mg/d,服用吉非替尼一月后检测血药及脑脊液药物浓度,病情进展后联合化疗或全脑放疗。［结果］ 8例患者病情稳定,29例肿瘤进展;无进展生存期为2.1~16月,中位无进展生存期6.2月;总生存期为2.1~21.9月,中位生存期8.7月。吉非替尼血药浓度、脑脊液浓度及脑脊液通透率与无进展生存期、总生存期均有正相关性,其中脑脊液浓度的相关性最大。在多种预后因素中,颅内病灶能否控制对无进展生存期及总生存期的影响具有统计学意义。［结论］ 吉非替尼明显改善了EGFR敏感突变肺腺癌脑转移患者的无进展生存期及总生存期,颅内病灶有效控制是改善患者预后的重要因素。     

吉非替尼同步γ射线立体定向外科加全脑放疗治疗非小细胞肺癌脑转移瘤的临床研究

评价吉非替尼同步伽马射线立体定向外科加全脑放疗治疗非小细胞肺癌（NSCLC）脑转移瘤的作用和获益影响因素。方法：回顾性分析23例NSCLC脑转移瘤患者接受吉非替尼同步γ射线立体定向外科治疗加全脑放疗后的疗效、疾病进展时间、总生存时间、预后影响因素及不良反应。结果：颅内病灶的疗效为：CR 2例,PR 16例,SD 3例,PD 2例,有效率78.3%（18/23）,疾病控制率91.3%（21/23）。全身病变的总体疗效为：CR 0例,PR 5例,SD 12例,PD 6例,有效率21.7%（5/23）,疾病控制率73.9%（17/23）。中位疾病进展时间为8.3个月,中位生存时间为12.8个月。单因素分析显示：KPS评分、肿瘤累及体积、病理类型、RPA分级为疾病进展时间预测因素（P均<0.05）;而KPS评分、肿瘤累及体积、RPA分级则是生存时间预测因素（P均<0.05）。吉非替尼不良反应主要为Ⅰ~Ⅱ度皮疹和腹泻,患者均可耐受。结论：吉非替尼同步γ射线立体定向外科治疗加全脑放疗后的治疗NSCLC脑转移瘤,有效率和疾病控制率高,具有较长的中位疾病进展时间和生存时间,不良反应轻微,是一种很有价值的治疗方法。其中,KPS评分、肿瘤体积、病理类型（腺癌）、RPA分级是影响获益和生存的重要因素。     

全脑放疗序贯吉非替尼治疗老年非小细胞肺癌伴脑转移的临床观察

目的 讨全脑放疗后序贯吉非替尼治疗老年非小细胞肺癌（NSCLC）伴脑转移患者的疗效及安全性。方法 30例老年NSCLC伴多发脑转移患者全脑放疗后口服吉非替尼250mg／d（治疗组）,直至病情进展或出现不可耐受的毒副反应;选择同期30例老年NSCLC伴多发脑转移患者全脑放疗后给予吉西他滨（1250mg／m2 静滴,d1、d8）治疗（对照组）,21天为1周期,共4个周期。比较两组患者的近期疗效、中位无进展生存期、中位总生存期及毒副反应。结果 治疗组颅内病灶有效率、疾病控制率和全身病变有效率、疾病控制率分别为43.3%、80.0％、40.0％和66.7％,对照组分别为13.3%、46.7％、13.3％和30.0％,两组差异均有统计学意义（P＜0.05）。治疗组的中位无进展生存期和中位生存期分别为7.4个月和12.8个月,对照组分别为4.2个月和8.2个月,两组差异均有统计学意义（P＜0.05）。对照组恶心呕吐、骨髓抑制的发生率分别为53.3％、66.7％,治疗组分别为3.3％、13.3％,两组差异均有统计学意义（P＜0.05）。两组腹泻、疲乏、肝功能异常等毒副反应的差异均无统计学意义（P＞0.05）。结论 全脑放疗后序贯吉非替尼治疗老年NSCLC伴脑转移的疗效确切,患者预后改善,且毒副反应可耐受。     

Gefitinib as palliative therapy for lung adenocarcinoma metastatic to the brain

BACKGROUND: Lung cancer is the leading cause of cancer deaths in most countries. In patients with metastases, such as the brain, the 1-year survival is 10% and most of these patients die in 1-3 months. Data from large phase II trials of non-small cell lung cancer (NSCLC) suggested that the histologic subtype of adenocarcinoma may be a prognostic factor for patients treated with gefitinib. To evaluate the efficacy of gefitinib in palliative therapy for advanced patients with adenocarcinoma and brain metastases, we conducted a phase II study. PATIENTS AND METHODS: Eligible patients had histologically confirmed adenocarcinoma and brain metastases confirmed with radiological studies. All eligible patients had undergone chemotherapy previously. From December 2003 to December 2004, 40 patients received 250mg doses of gefitinib daily. The symptomatic response, survival, and toxicity were recorded. RESULTS: The overall objective response rate was 32% with a disease control rate of 77%. Altogether, 45% of the patients experienced symptom improvement. The median progression-free survival and overall survival were 9.0 months and 15.0 months, respectively. Gefitinib was well-tolerated, with cutaneous reactions as the most frequent toxicity. CONCLUSIONS: Our data suggest that gefitinib has promising activity in palliative therapy for patients with advanced lung adenocarcinoma and brain metastasis.     

吉非替尼对于化疗失败的晚期肺腺癌的疗效及生存观察

目的：观察吉非替尼在化疗失败的晚期肺腺癌中的疗效、生存时间及影响因素。方法：收集２１例初始化疗失败的转移性肺腺癌,应用吉非替尼２５０ｍｇ口服,每日１次,直至出现有客观证据的病情进展,或出现不可耐受的不良反应。用Ｋａｐｌａｎ-Ｍｅｉｅｒ法拟定生存曲线,采用Ｌｏｇｒａｎｋ检验分析生存因素。结果：２１例患者中ＣＲ３例（１４.３％）,ＰＲ例８（３８.１％）,ＳＤ３例（１４.３％）,ＰＤ７例（３３.３％）。客观缓解率为５２.４％,疾病控制率为６６.７％。中位无进展生存时间（ＰＦＳ）为６个月,中位生存时间（ＯＳ）为８个月。１年生存率为３３.３％（７／２１）,２年生存率为９５％（２／２１）。好的ＰＳ评分与生存期延长显著相关（Ｐ＜０.０１）。结论：吉非替尼对既往化疗失败的晚期肺腺癌疗效好,能有效改善生存时间,体力状态评分与吉非替尼治疗的生存时间相关。     

Efficacy of gefitinib for non-adenocarcinoma non-small-cell lung cancer patients harboring epidermal growth factor receptor mutations: a pooled analysis of published reports

The efficacy of gefitinib for patients with non-adenocarcinoma non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations is unclear, because only a small percentage of patients enrolled in the clinical trials to evaluate the efficacy of gefitinib for tumors harboring EGFR mutation were non-adenocarcinoma NSCLC. A pooled analysis was conducted to clarify the efficacy of gefitinib for non-adenocarcinoma NSCLC patients harboring EGFR mutations. A systematic search of the PUBMED databases was conducted to identify all clinical reports that contained advanced non-adenocarcinoma NSCLC patients harboring EGFR mutations and treated with gefitinib. The selected patients were advanced non-adenocarcinoma NSCLC patients harboring EGFR mutations who were treated with gefitinib and described in reports containing the data of the histology, status of EGFR mutations and response to gefitinib. This study selected 33 patients from 15 reports. Twenty-seven and three of the 33 patients were squamous cell carcinoma and adenosquamous cell carcinoma, respectively. One patient each had large-cell carcinoma, pleomorphic carcinoma and spindle cell carcinoma. Twenty-one patients (64%) had sensitive EGFR mutations. The response rate (RR), disease control rate (DCR) and median progression-free survival (mPFS) was 27%, 67-70% and 3.0 months, respectively. These factors were statistically significantly inferior in the non-adenocarcinoma NSCLC patients harboring EGFR mutations to adenocarcinoma patients harboring EGFR mutations selected from the same published reports (RR: 27%vs 66%, P = 0.000028; DCR: 67-70%vs 92-93%, P = 0.000014; mPFS: 3.0 vs 9.4 months, P = 0.0001, respectively). Gefitinib is less effective in non-adenocarcinoma NSCLC harboring EGFR mutations than adenocarcinoma harboring EGFR mutations.     

Gefitinib as a first-line therapy of advanced or metastatic adenocarcinoma of the lung in never-smokers.

PURPOSE: A subset of patients with adenocarcinoma of the lung who had never smoked cigarettes showed excellent tumor responses to gefitinib therapy. To evaluate the efficacy of gefitinib as a first-line therapy in this subgroup of patients, we conducted a phase II study. EXPERIMENTAL DESIGN: Eligible patients had no smoking history, stage IIIB or IV adenocarcinoma, Eastern Cooperative Oncology Group performance status 0 to 2, and adequate organ functions. Treatment consisted of daily oral administration ofF 250 mg gefitinib for 28 days until disease progression. Responses were assessed after every two cycles of therapy. RESULTS: Of 37 patients enrolled, 36 were assessed for response. Twenty-five patients (69%) had partial response, 4 (11%) had stable disease, and 7 (19%) had progressive disease. Of 10 patients with evaluable brain metastases, 7 had objective responses in both intracranial and extracranial lesions, 1 had stable disease in the brain and dramatic response in the extracranial lesions, and 2 had progressive disease in both sites. After a median follow-up of 48 weeks (range, 4-70 weeks), 26 patients had disease progression, with median progression-free survival of 33 weeks, and 9 patients died, all due to disease progression. The median survival time has not been reached yet but the estimated 1-year survival rate was 73%. Common toxicities were skin rash and mild diarrhea but there was no significant hematologic toxicity. CONCLUSIONS: Gefitinib showed very dramatic antitumor activity, even in the brain, with unprecedented survival outcome in never-smoker adenocarcinoma patients. These data support the use of gefitinib as a first-line therapy in this particular subgroup.     

High frequency of epidermal growth factor receptor mutations with complex patterns in non-small cell lung cancers related to gefitinib responsiveness in Taiwan.

PURPOSE: Epidermal growth factor receptor (EGFR) mutations related to gefitinib responsiveness in non-small cell lung cancer have been found recently. Detection of EGFR mutations has become an important issue for therapeutic decision-making in non-small cell lung cancer. EXPERIMENTAL DESIGN: Mutational analysis of the kinase domain of EGFR coding sequence was done on 101 fresh frozen tumor tissues from patients without prior gefitinib treatment and 16 paraffin-embedded tumor tissues from patients treated with gefitinib. Detection of phosphorylated EGFR by immunoblot was also done on frozen tumor tissues. RESULTS: The 101 non-small cell lung cancer tumor specimens include 69 adenocarcinomas, 24 squamous cell carcinomas, and 8 other types of non-small cell lung cancers. Mutation(s) in the kinase domain (exon 18 to exon 21) of the EGFR gene were identified in 39 patients. All of the mutations occurred in adenocarcinoma, except one that was in an adenosquamous carcinoma. The mutation rate in adenocarcinoma was 55% (38 of 69). For the 16 patients treated with gefitinib, 7 of the 9 responders had EGFR mutations, and only 1 of the 7 nonresponders had mutations, which included a nonsense mutation. The mutations seem to be complex in that altogether 23 different mutations were observed, and 9 tumors carried 2 mutations. CONCLUSIONS: Data from our study would predict a higher gefitinib response rate in lung adenocarcinoma patients in Chinese and, possibly, other East Asian populations. The tight association with adenocarcinoma and the high frequency of mutations raise the possibility that EGFR mutations play an important role in the tumorigenesis of adenocarcinoma of lung, especially in East Asians.     

Gefitinib combined with γ-ray stereotactic body radiation therapy has better efficacy than gefitinib alone for senile lung adenocarcinoma patients with EGFR mutations as first-line regimen

Objective： The senile lung adenocarcinoma patients harboring an activating epidermal growth factor receptor （EGFR） mutation shows good and rapid response to EGFR tyrosine kinase inhibitors （TKIs）. Whether gefitinib combined with y-ray stereotactic body radiation therapy has better efficacy than gefitinib alone for senile lung adenocarcinoma patients with EGFR mutations as first-line regimen is still under investigation. Methods： The 42 senile lung adenocarcinoma patients with EGFR mutations were divided into 2 groups according to the therapy method. Group A was the 22 patients treated with gefitinib combined with y-ray stereotactic body radiation therapy （SBRT）. Group B was the 20 patients treated with gefitinib alone. All of the patients received gefitinib of 250 mg/d from the first day until disease progression or other reasons. The patients of Group A were treated with y-ray stereotactic body radiation therapy from the second day. Radiation fields included the primary lesions and the integration of lymph nodes. Dose curve of this group was 50%-80%. Encircled dose was 4.0-6.5 Gy per fraction and the range of total dose was 40-52 Gy. We treated the patients 8-12 times and treated five times every week. Results： All the patients were examined by enhanced double helix CT at the second month. The tumor response rate （RR） of group A was 81.8% （18/22）. Disease control rate （DCR） was 90.9% （20/22）. The median overall survival （OS） was 24.2 months （range 8-58 months ） and the progression-free survival （PFS） was 18.6 months. The overall 1-year survival rate was 72.3% （16/22） and 2-year survival rate was 54.5% （12/22）. The main side effects included skin rash and diarrhea. The RR of group B was 50.0 % （10/20）. DCR was 75.0% （15/20）. OS was 17.4 months （range 6-32 months ） and PFS was 12.1 months. The overall 1-year survival rate was 60.0% （12/20） and 2-year survival rate was 40.0% （8/20）. The main side effects included skin rash and diarrhea. The g     

晚期肺腺癌EMT和EGFR突变状态的关系及其对吉非替尼治疗疗效的影响

目的：探讨晚期肺腺癌上皮间质转化（EMT）与表皮生长因子（EGFR）突变的关系及其对吉非替尼治疗敏感性的关系。方法通过检测78例晚期肺腺癌EGFR突变情况和E-cadherin/β-catenin表达情况,对EGFR突变的晚期肺腺癌患者一线使用吉非替尼,EGFR未突变的晚期肺腺癌一线化疗失败后二线使用吉非替尼治疗,观察吉非替尼治疗的疗效和无进展生存时间（PFS）。结果晚期肺腺癌EGFR突变患者E-cadherin表达高于EGFR未突变患者。EGFR突变且E-cadherin/β-catenin阳性表达者疾病控制率（DCR）略高于异常表达者,虽差异无统计学意义,但EGFR突变同时E-cadherin/β-catenin阳性表达者显示了更长的PFS。EGFR未突变的晚期肺腺癌二线吉非替尼治疗患者临床获益率低。结论晚期肺腺癌患者EGFR突变者常伴随E-cadherin高表达,同时存在EG-FR突变和E-cadherin/β-catenin高表达者显示更长的PFS;不建议EGFR未突变的晚期肺腺癌病例二线使用吉非替尼。     

Gefitinib as first-line treatment in elderly epidermal growth factor receptor-mutated patients with advanced lung adenocarcinoma: results of a Nagano Lung Cancer Research Group study

Introduction

Feasibility of gefitinib therapy in elderly patients with non–small-cell lung cancer is uncertain. This phase II study aimed to investigate the efficacy and usefulness of gefitinib therapy as a first-line treatment for elderly patients who have advanced lung adenocarcinoma with epidermal growth factor receptor (EGFR) mutations.

Patients and Methods

We enrolled chemotherapy-naïve advanced lung adenocarcinoma patients aged 75 years or older. Patients were administered gefitinib (250 mg) once daily until progression or unacceptable toxicity. The primary endpoint was response rate (RR), and secondary endpoints were disease control rate (DCR; defined as complete response [CR] plus partial response [PR] plus stable disease [SD]), progression-free survival (PFS), overall survival (OS), and toxicity profile.

Results

Between April 2008 and November 2009, 17 lung adenocarcinoma patients were enrolled. Overall RR was 59% (95% confidence interval [CI]: 33% to 81%), with 2 patients achieving CR and 8 PR. SD was noted in 5 patients, and DCR was 88% (95% CI: 62% to 98%). Median PFS was 12.9 months (95% CI: 2.2 to 23.6 months), and median OS had not yet been reached. Major grade 3 toxicities were skin rash (12%) and increased levels of aspartate aminotransferase or alanine aminotransferase (18%).

Conclusion

First-line treatment with gefitinib was effective and well-tolerated in elderly patients with EGFR mutations.     

Gefitinib in patients with brain metastases from non-small-cell lung cancer: a prospective trial.

BACKGROUND: Brain metastases are a common occurrence in patients with non-small-cell lung cancer (NSCLC). Whole-brain radiotherapy (WBRT) is the standard therapy; more aggressive approaches such as surgery or radiosurgery are indicated in a subset of patients only. The role of systemic treatments remains controversial. Gefitinib is an oral, highly tolerable, specific inhibitor of epidermal growth factor receptor-associated tyrosine kinase, which has shown activity in chemotherapy pre-treated NSCLC. The aim of this study was to evaluate the activity and safety of gefitinib in NSCLC patients with brain metastases. PATIENTS AND METHODS: From January 2001 to May 2003, 41 consecutive NSCLC patients with measurable brain metastases were treated with gefitinib, given orally at daily dose of 250 mg. Thirty-seven patients had received previous chemotherapy and 18 patients had been treated previously with WBRT, completed at least 3 months before entering the trial. RESULTS: A partial response (PR) was observed in four patients (10%), with stable disease (SD) in seven cases, for an overall disease control (DC) rate (DC=PR+SD) of 27% (95% confidence interval 13% to 40%). Median duration of PR was 13.5 months. Median progression-free survival (PFS) of the whole population was 3 months. DC rate was higher in patients pre-treated with WBRT (P=0.05) and with adenocarcinoma histological type (P=0.08); adenocarcinoma patients had also a longer PFS (P=0.04). Toxicity was mild and consisted of grade 1/2 skin toxicity and diarrhoea, occurring in 24% and 10% of patients, respectively. CONCLUSIONS: Gefitinib can be active on brain disease in NSCLC patients. Since the results of standard therapy for brain metastases in this clinical setting are particularly disappointing, gefitinib appears to be a possible new treatment option.     

Efficacy of EGFR tyrosine kinase inhibitors for non-adenocarcinoma NSCLC patients with EGFR mutation

Purpose

The epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) gefitinib and erlotinib have shown dramatic response rate (RR) and significant prolongation of progression-free survival (PFS) in non-small-cell lung cancer (NSCLC) patients with EGFR mutation. Since only a few patients with non-adenocarcinoma histology have been enrolled in clinical trials, the efficacy of EGFR TKIs in non-adenocarcinoma NSCLC patients with EGFR mutation has not yet been fully determined.

Methods

We retrospectively analyzed clinical outcomes, including RR, PFS, and OS, in patients who were treated with the EGFR TKIs gefitinib or erlotinib and compared the results with those of adenocarcinoma patients with EGFR mutation and non-adenocarcinoma patients with wild-type EGFR.

Results

Among 250 patients with non-adenocarcinoma of the lung who underwent EGFR mutation genotyping, 21 were found to have an EGFR mutation (8.4?%). Twelve of the 21 patients were treated with the EGFR TKIs gefitinib (n?=?6) or erlotinib (n?=?6). The most common mutation was exon 19 deletion (n?=?7). The RR and disease control rate for 12 patients receiving EGFR TKIs were 50 and 75?%, respectively. The median PFS was 3.67?months (95?% CI: 1.34?C5.99), which was significantly lower than that of 269 adenocarcinoma patients with EGFR mutation (13.53?months) but better than that of 32 non-adenocarcinoma patients with wild-type EGFR (1.83?months) who were treated with EGFR TKIs.

Conclusions

The results of this study show that the EGFR mutation rate in Korean patients with non-adenocarcinoma of the lung is relatively high and that the clinical outcomes of EGFR TKIs are modest.