吉非替尼治疗晚期非小细胞肺癌的研究进展

吉非替尼（gefitinib）是一种靶向抗癌药物,是表皮生长因子受体（EGFR）酪氨酸激酶（PTK）抑制剂。具有减慢肿瘤细胞增值,有效延缓病情进展,改善患者生存质量,延长患者生存期限的作用。适用于既往接受过化疗的晚期局部或转移性非小细胞肺癌（NSCLC）二线或三线的治疗。     

吉非替尼治疗晚期非小细胞肺癌36例临床观察

目的:观察吉非替尼(Gefitinib)治疗晚期非小细胞肺癌(NSCLC)的疗效及毒副作用。方法:对不能耐受化疗或化疗失败的晚期NSCLC患者36例,其中属于二线或二线以上治疗者24例(66.7%),给予吉非替尼250mg,1次/d,口服,服药时间至少30天,定期进行疗效及毒副作用的评价,一旦出现不可耐受的毒副作用或疾病进展即停药。结果:36例中完全缓解(CR)1例,部分缓解(PR)13例,稳定(SD)12例,进展(PD)10例,有效(CR PR)14例(38.9%),疾病控制(CR PR SD)26例(72.2%),中位肿瘤进展时间为3.5个月,1年生存14例(38.9%)。常见毒副作用为Ⅰ、Ⅱ度皮疹和腹泻,Ⅲ度不良反应2例(5.6%),无因毒副作用严重而停药者。结论:吉非替尼治疗晚期NSCLC疗效明显,临床获益率高,体力状况评分较好者客观缓解率及生存期更好。     

吉非替尼治疗62例中晚期非小细胞肺癌疗效分析

目的观察应用吉非替尼治疗对化疗耐药的中晚期非小细胞肺癌的疗效和不良反应,以及对生活质量的影响。方法62例既往化疗失败的Ⅲb～Ⅳ期非小细胞肺癌患者,口服吉非替尼250mg/d,服药至病情进展或出现不能耐受的不良反应,观察吉非替尼的疗效和不良反应,以及患者的生活质量。结果62例患者均可评价疗效,其中CR2例,PR16例,SD38例,PD6例,总有效率（RR）为29.0%（18/62）,临床受益率90.3%（56/62）,ECOG评分稳定及改善为71.0%（44/62）。最常见的不良反应为皮疹（27.4%）,多伴发皮肤干燥和瘙痒。结论吉非替尼对化疗耐药的中晚期非小细胞肺癌疗效确切,改善生活质量且不良反应轻,耐受性好。     

吉非替尼治疗晚期非小细胞肺癌临床观察

目的 总结表皮生长因子受体酪氨酸激酶抑制剂吉非替尼治疗晚期非小细胞肺癌的临床经验及体会。方法 从2005年5月至2007年1月有30例晚期非小细胞肺癌患者进入研究,所有患者均为Ⅲ至Ⅳ期,吉非替尼剂量为250mg/次,口服,每天1次。结果 30例患者均可评价,获得PR7例（23.3%）,SD12例（40.0%）,PD11例（36.7%）,总的疾病控制率63.3%。未出现3至4级的毒性反应。结论 吉非替尼是一种比较有效的新型分子靶向治疗药物,不良反应轻微,可用于晚期非小细胞肺癌的治疗。     

吉非替尼治疗对化疗耐药的中晚期非小细胞肺癌62例疗效分析

目的观察应用吉非替尼治疗对化疗耐药的中晚期非小细胞肺癌的疗效和不良反应,以及对生活质量的影响。方法62例既往化疗失败的Ⅲb～Ⅳ期非小细胞肺癌患者,口服吉非替尼250 mg/d,服药至病情进展或出现不能耐受的不良反应,观察吉非替尼的疗效和不良反应,以及患者的生活质量。结果62例患者均可评价疗效,其中CR 2例,PR 16例,SD 38例,PD 6例,总有效率（RR）为29.0%（18/62）,临床受益率90.3%（56/62）,ECOG评分稳定及改善为71.0%（44/62）。最常见的不良反应为皮疹（27.4%）,多伴发皮肤干燥和瘙痒。结论吉非替尼对化疗耐药的中晚期非小细胞肺癌疗效确切,改善生活质量且不良反应轻,耐受性好。     

吉非替尼治疗对化疗耐药的晚期非小细胞肺癌32例临床观察

目的：观察应用吉非替尼治疗对化疗耐药的中晚期非小细胞肺癌的疗效和不良反应,以及对生活质量的影响。方法：对32例既往化疗失败的Ⅳ期非小细胞肺癌患者,口服吉非替尼250mg／d,服药至病情进展或出现不能耐受的不良反应,观察吉非替尼的疗效和不良反应,以及对患者生活质量的影响。结果：30例可评价疗效患者中,CR2例,PR12例,SD5例,PD11例。总有效率为46．7％（14／30）,临床获益率为63.3％（19／30）。ECOG评分稳定及改善率为78．1％（25／32）。最常见的不良反应为皮疹（11／32）。结论：吉非替尼对化疗耐医科的中完期非小细胞肺癌疗效确切,改善生活质量,而且不良反应轻,耐受性好,值得在临床推广应用。     

吉非替尼治疗34例晚期非小细胞肺癌的临床观察

目的：探讨晚期非小细胞肺癌（NSCLC）患者应用吉非替尼治疗的效果及毒副作用。方法：34例经放化疗失败的非小细胞肺癌晚期患者,均发生远处转移。口服吉非替尼250mg/次,每天1次,服药中位时间为4个月。结果：34例晚期NSCLC患者,无一例完全缓解（CR）,19例部分缓解（PR）,10例稳定（SD）,5例进展（PD）,全组有效率（CR＋PR）为55.9%,临床获益率（CR＋PR＋SD）为85.3%。中位生存期5.6个月,1年生存率为47.1%（16/34）。结论：吉非替尼治疗晚期NSCLC的疗效较好,毒副作用较轻,可以耐受。     

吉非替尼治疗非小细胞肺癌的疗效及对血清中表皮生长因子受体的影响

目的探讨吉非替尼佐治非小细胞肺癌的临床疗效,并观察治疗后血清中表皮生长因子受体（EGFR）的表达,以期为临床工作提供支持。方法收集我院确诊的112例非小细胞肺癌患者,依患者的人院顺序分为观察组与对照组,观察组共56例,应用吉非替尼治疗;对照组共56例,应用常规化疗,观察治疗的效果及治疗后血清中~EGFR的差别。结果观察组的疗效明显优于对照组,治疗后观察组患者血清中EGFR的表达明显低于对照组。结论吉非替尼治疗非小细胞肺癌效果较好,并能有效下调血清中EGFR的表达,临床中可以积极应用。     

非小细胞肺癌EGFR基因突变与吉非替尼疗效的相关性研究

目的探索铜陵地区非小细胞肺癌EGFR基因突变率,观察EGFR基因的突变与吉非替尼的疗效的关系。方法2009年1月至2010年12月安徽省铜陵市人民医院诊治的符合入组条件的晚期NSCLC 34例,对其病理标本使用ARMS法进行EG-FR基因突变18～21外显子的检测。所有病例均给予口服吉非替尼250 mg/d,1次/d,持续服用直到疾病进展或出现不可耐受的毒副反应。观察症状的控制、临床疗效、无疾病进展生存时间(PFS)、总生存时间(OS)和不良反应。结果铜陵地区34例NSCLC患者EGFR基因突变的检出阳性率59.09%。34例吉非替尼治疗NSCLC疗效总有效率(16/34)47.06%,经Fisher精确检验显示无吸烟史、EGFR突变、肺内有播散有效率高,与有吸烟史、无EGFR突变、无肺内有播散者相比,差异有统计学意义(P0.05)。Logistic多因素回归分析显示仅EGFR突变、肺内有播散为独立影响因素。Cox模型回归分析显示EGFR基因突变使肿瘤进展的风险降低了70%。结论铜陵地区NSCLC EGFR基因突变率较高,EGFR突变可以较好地预测吉非替尼治疗晚期NSCLC的疗效,降低了肿瘤进展的风险,且安全性好。     

吉非替尼治疗晚期非小细胞肺癌疗效观察

目的:评价采用吉非替尼治疗化疗失败的局部晚期或转移性非小细胞肺癌(NSCLC)的疗效及不良反应。方法:42例化疗失败的局部晚期或转移性NSCLC患者予吉非替尼250mg每日1次口服直至病情进展或出现不可耐受的不良反应,评价近期疗效、生存期、生活质量及毒副反应。结果:CR1例、PR11例、SD18例、PD12例,有效率为28.57、临床受益率为71.43、中位无疾病进展时间为4个月、中位生存期为10个月、1年生存率为45.23;生活质量明显改善者占61.90;药物不良反应多为Ⅰ～Ⅱ度皮疹及腹泻。结论:吉非替尼应用于化疗失败的局部晚期或转移性NSCLC的二线或三线治疗疗效确切,不良反应轻微,而且可以明显改善患者的生活质量。     

Erlotinib as a salvage treatment for patients with advanced non-small cell lung cancer after failure of gefitinib treatment

Background  Several clinical trials showed that erlotinib was effective after the failure of gefitinib in advanced non-small cell lung cancer (NSCLC). The aim of this study was to evaluate the feasibility of erlotinib treatment after the failure of gefitinib based on the data from our hospital.

Methods  The clinical data of 20 patients with advanced NSCLC who were admitted to Shanghai Chest Hospital from August 2007 to December 2008 were retrospectively analyzed. All of the patients were given erlotinib treatment after the failure of gefitinib. Survival analysis was made by Kaplan-Meier method. The Cox regression model was performed to analyze the relationship between the influential factors and the erlotinib progression-free survival (PFS).

Results  Five patients had a partial response (PR), nine patients had stable disease (SD) and six patients had progressive disease (PD) with gefitinib treatment. The median PFS was 277 days (95% CI 0–566). No patient had a PR, seven had SD and fourteen PD with the erlotinib therapy. The median PFS was 31 days (95% CI 9.1–52.9). The response rate (RR) was 0, and the disease control rate (DCR) was 35% (7/20). Cox regression analysis demonstrated that sex (P=0.96), age (P=0.89), smoking history (P=0.78), performance status (PS) (P=0.98), gefitinib efficacy (P=0.90) and whether chemotherapy was applied between using the two drugs (P=0.45) had no significant correlation with erlotinib PFS. Fifteen patients had epidermal growth factor receptor (EGFR) mutation status determined. There were five cases got SD with the erlotinib treatment in ten mutation negative (wild-type) patients. No SD was recorded in the five mutation positive patients.

Conclusions  The efficacy of erlotinib treatment after gefitinib failure was limited. However, the patients who are EGFR mutation negative can probably benefit from erlotinib treatment after gefitinib failure.

     

Recurrence patterns of advanced non-small cell lung cancer treated with gefitinib

Background Gefitinib is widely used in the treatment of advanced non-small cell lung cancer (NSCLC).However,only a small number of reports have described initial failure sites in patients treated with ...     

吉非替尼治疗晚期非小细胞肺癌的临床研究

[目的]观察吉非替尼(Gefitinib)治疗含铂类化疗失败的晚期非小细胞肺癌的疗效及毒副作用.[方法]对76例含铂类化疗失败的晚期非小细胞肺癌患者给予吉非替尼250 mg/d口服治疗,持续服用直到疾病进展或出现不可耐受的毒副作用.[结果]76例患者中完全缓解(CR)3例(3.9%),部分缓解(PR)19例(25.0%),稳定(SD)30例(39.4%).总有效率(RR)为28.9%.临床获益率为68.3%(52/76).有效患者的中位缓解时间为8.3个月,中位肿瘤进展时间(TTP)为5.8个月,中位总生存期(OS)为12个月,1年生存率为47.6%.女性患者的有效率显著高于男性患者(P＜0.001).与药物相关的毒副作用依次为:皮疹29例(38.0%),腹泻16例(21.0%),皮肤干燥11例(14.43%),搔痒12例(15.7%).其他亦可出现恶心、ALT轻度升高等.[结论]吉非替尼可有效治疗含铂类化疗失败的晚期非小细胞肺癌.吉非替尼的毒副作用可耐受.     

Efficacy and safety of gefitinib as monotherapy for Chinese patients with advanced non-small cell lung cancer

PLATINUM-BASED CHEMOTHERAPY CAN IMPROVE THE SURVIVAL AND QUALITY OF LIFE OF PATIENTS WITH LOCALLY ADVANCED AND METASTATIC LUNG CANCER. SECOND-LINE DOCETAXEL MONOTHERAPY CAN IMPROVE OVERALL SURVIVAL FOLLOWING THE FAILURE OF FIRST LINE CHEMOTHERAPY. HOWEVER, MANY LIMITING FACTORS SUCH AS POOR PERFORMANCE STATUS, ADVANCED AGE, ADVERSE EFFECTS OF CHEMOTHERAPY AND RELUCTANCE …     

Comparison of three methods for detecting epidermal growth factor receptor mutations in plasma DNA samples of Chinese patients with advanced non-small cell lung cancer

Background  Epidermal growth factor receptor (EGFR) mutations can predict tumor response to tyrosine kinase inhibitors (TKIs). Detecting EGFR mutations in plasma DNA samples in patients with advanced non-small cell lung cancer is challenging and promising. We compared three methods for detecting plasma EGFR mutations, including direct DNA sequencing, denaturing high-performance liquid chromatography (DHPLC) and Scorpions Amplification Refractory Mutation System (Scorpions ARMS).

Methods  Plasma DNA samples from 73 patients with stage IIIB to IV adenocarcinoma were analyzed for EGFR mutations in exons 19 (deletion mutation) and 21 (L858R mutation) using direct DNA sequencing, DHPLC and Scorpions ARMS. Sensitivities of the three methods were compared and the relationship between EGFR mutations and patients’ survival was analyzed.

Results  In 73 patients, we detected EGFR mutations in 5 samples (6.9%) by direct DNA sequencing, in 22 samples (30.1%) by DHPLC, and in 28 samples (38.4%) by Scorpions ARMS. EGFR mutations were found in 13 samples in exon 19 and in 9 samples in exon 21 by DHPLC, while we found mutations in 15 samples in exon 19 and in 13 samples in exon 21 by Scorpions ARMS. Among the 73 patients, there was 90.4% concordance between DHPLC and Scorpions ARMS (66/73, κ=0.79, P=0.07). Of the 73 patients, 46 patients were treated with gefitinib, including 18 patients with mutations and 28 patients without mutations as determined by Scorpions ARMS. The 18 patients with mutations had a significantly longer progression-free survival (PFS) time (median PFS was 21.0 months) than the 28 patients without mutations (median PFS was 7.0 months) (P=0.022).

Conclusions  Among the three methods for detecting EGFR mutations in plasma DNA samples of patients with advanced lung adenocarcinoma, direct gene sequencing had the lowest sensitivity, while Scorpion ARMS showed the highest mutation detecting capability. DHPLC is slightly less sensitive than Scorpion ARMS. EGFR mutations in exons 19 (deletion mutation) and 21 (L858R mutation) predict a longer PFS.

     

非小细胞肺癌中表皮生长因子受体基因突变的筛查

目的检测非小细胞肺癌患者的表皮生长因子受体(EGFR)基因外显子的突变情况。方法收集24例肺腺癌和25例肺鳞癌手术标本,抽提组织DNA,对EGFR基因的1-28号外显子进行扩增并测序,筛查EGFR基因的突变。结果在8例肺腺癌患者中检出EGFR突变,在肺鳞癌患者中未检测到突变。检测到的突变位点位于19-21号外显子内,且均为非吸烟患者,占非吸烟肺腺癌患者的61.5%(8/13)。结论 EGFR基因突变在非吸烟的肺腺癌患者具有较高的发生率,突变主要集中发生于19-21号外显子。     

Manifestation of leukoencephalopathy in a patient with advanced non-small cell lung cancer following treatment with gefitinib

The present case is a patient with advanced non-small cell lung cancer (NSCLC) who developed leukoencephalopathy following radiotherapy and gefitinib treatments. There are rarely reports of such incidences because the median survival period of advanced NSCLC is only ten months. The features of leukoencephalopathy in this case were atypical for radiation leukoencephalopathy, so it was suspected that the leukoencephalopathy was associated with gefitinib.

     

Improvements in quality of life and disease-related symptoms in patients with advanced non-small cell lung cancer treated with gefitinib

Most patients with advanced non-small cell lung cancer （NSCLC） experienced mild to severe disease-related symptoms including fatigue, loss of appetite, chest pain, dyspnoea, cough and hemoptysis. These symptoms hamper the patients＇ ability to carry out daily activity and the deteriorating of disease-related symptoms is often associated with poor performance status, which may decrease the treatment options for patients. Furthermore,     

非小细胞肺癌生存分析

[目的] 分析非小细胞肺癌预后的相关因素,为非小细胞肺癌的预后判断提供科学依据。[方法] 对具有明确组织学类型和临床分期的306例非小细胞肺癌患者,进行查阅病历并随访,从患者个体信息、患病情况、治疗方法等3个方面收集信息。[结果] 随访的306例患者中失访32人,随访率89.54%。患者总中位生存期为16个月,1、3、5年生存率分别为66%、16%、9%。多因素分析显示CEA水平、症状出现与就诊时间差、PS功能状态评分(PS评分)为预后的独立影响因素,卡氏功能状态(KPS)评分、手术为预后的保护性因素。[结论] 癌胚抗原(CEA)水平、症状出现与就诊时间差、KPS评分、PS评分、手术可作为判断非小细胞肺癌预后的指标。