厄洛替尼二线治疗晚期非小细胞肺癌36例

肺癌是最常见的恶性肿瘤之一,而非小细胞肺癌(non-small cell lung cancer,NSCLC)占肺癌的80%以上.NSCLC不容易早期发现,多数患者在确诊时已属晚期,失去了手术机会,其中位生存期为8～10个月;患者接受以铂类为基础的联合化疗失败后,再次治疗后的中位生存期为5～7个月.     

厄洛替尼治疗晚期非小细胞肺癌的临床观察

目的 观察厄洛替尼单药治疗晚期非小细胞肺癌(NSCLC)的疗效和不良反应.方法 104例晚期NSCLC患者给予厄洛替尼150 mg口服治疗,每日1次,服用至疾病进展或出现不可耐受的不良反应.采用实体瘤的疗效评价标准评价疗效.采用美国国家癌症研究所毒性评价标准评价不良反应.结果 104例患者均可评价疗效,客观有效率为27.9%(29/104),疾病控制率为76.0%(79/104),中位无进展生存时间为5.1个月,中位生存时间为13.1个月,1年总生存率为61.5%.多因素生存分析显示,PS评分为0～1分、腺癌和治疗后出现皮疹的患者具有显著的生存优势(均P<0.05);而吸烟和肝转移则显著增加了死亡风险(均P<0.05).厄洛替尼治疗晚期NSCLC最常见的不良反应是皮疹和腹泻,发生率分别为73.1%和41.3%.不良反应多为1～2级,3～4级不良反应的发生率仅为6.7%.结论 厄洛替尼治疗晚期NSCLC的疗效确切,患者耐受性良好,可作为化疗失败、不适合或拒绝接受化疗的晚期NSCLC患者的治疗选择.     

皮疹与厄洛替尼治疗晚期非小细胞肺癌疗效相关性研究

背景与目的:厄洛替尼(erloti nib)是治疗非小细胞肺痛(non-smaIl cell lung cancer,NSCLC)的一种靶向性抗肿瘤约物,皮疹是使用厄洛替尼的主要不良反应,本研究旨住探讨不同程度皮疹与厄洛替尼治疗晚期NSCLC疗效是否存在相关性.方法:对接受过1个周期以上含铂化疗方案失败的晚期NSCLC患者,每日口服150 mg厄洛替尼直至疾病进展,将出现0、1～2、3度皮疹患者分为3组,观察出现不同程度皮疹的患者接受厄洛替尼治疗后的疗效和生存时间.采用Kaplan-Meier法分析比较各组间的生存率差异.结果:0度皮疹组共自3例,有效率为0(0/3),1～2度皮疹组有36例,有效率为22.2%(8/36),3度皮疹组有9例,有效率为88.8%(8/9),各皮疹组之间有效率差异具有统计学意义(P<0.001).1～2度皮疹出现中位时间为7 d,3度皮疹出现中何时间为21 d.0、1～2和3度皮疹组的中位无进展时间分别为2、4和10个月,各组之间差异无统计学意义(P=0.067).中位生存时间分别为5、6和23个月,各组之间差异亦无统计学意义(P=0.146).0～2度和3度皮疹组中位无进展生存时间分别为3和10个月,2组之间差异有统计学意义(P=0.036);中位生存时间分别为6和23个月,2组之间差异无统计学意义(P=0.073).结论:对工不同程度皮疹与厄洛替尼治疗晚期NSCLC有效率之间存在一定相关性,皮疹较重患者有效率较高,3度皮疹患者无进展生存时间长于其他患者.     

厄洛替尼治疗化疗后进展的晚期非小细胞肺癌的近期疗效观察

目的 观察厄洛粹尼治疗化疗后进展的晚期非小细胞肺癌(NSCLC)的疗效和不良反应.方法 化疗后进展的12例晚期NSCLC患者,口服厄洛替尼150 mg/d,1个月后进行疗效评价.疾病无进展者继续服用,之后每月对接受治疗者进行疗效评价,并密切观察不良反应.结果 12例患者均可评价疗效,其中完全缓解1例,部分缓解2例,疾病无变化4例,疾病进展5例;有效率为25.0%(3/12),疾病控制率为58.3%(7/12),临床受益率为41.7%(5/12).厄洛替尼治疗的主要不良反应为皮疹和腹泻,全组无一例患者因不能耐受不良反应而终止治疗.结论 厄洛替尼对化疗后进展的晚期NSCLC具有一定的疗效,且不良反应轻,患者能够耐受.     

厄洛替尼治疗晚期非小细胞肺癌的临床观察

目的观察厄洛替尼治疗晚期非小细胞肺癌的疗效及不良反应。方法32例经放、化疗治疗失败的非小细胞肺癌患者,其中6例肿瘤局限于胸腔内,26例已有远处转移,厄洛替尼剂量为每天150mg,口服,每天1次,直到肿瘤进展或因不良反应不能耐受而中止治疗。结果32例患者中,完全缓解1例,部分缓解9例,稳定13例,进展9例,全组有效率为31.3%,疾病控制率为71.9%,中位生存期7.8月,1年生存率为45.3%。主要不良反应是皮疹和腹泻,不需要特殊处理。结论厄洛替尼对放、化疗失败的晚期非小细胞肺癌有较好的治疗效果,且不良反应轻。     

厄洛替尼治疗晚期非小细胞肺癌的临床观察

目的 探讨厄洛替尼治疗晚期非小细胞肺癌(NSCLC)的疗效及毒副反应.方法 对26例晚期不能耐受化疗及不愿接受化疗的晚期NSCLC用厄洛替尼治疗,直到病变进展或出现不可耐受的毒副反应而终止,观察其疗效和毒副反应.结果 26 例晚期NSCLC中,CR 0 例,PR 5 例,SD 11例,PD 10例,有效率为19.23%,疾病控制率为61.54%.中位肿瘤进展时间为5.7个月,中位生存时间为11.5个月.主要的毒副反应为皮疹、皮肤瘙痒、腹泻和恶心呕吐,多为Ⅰ～Ⅱ度,对症处理后可缓解.结论 厄洛替尼治疗晚期NSCLC疗效明确,毒副反应轻.     

血清CEA水平与厄洛替尼治疗晚期非小细胞肺癌疗效的相关性分析

目的:探讨血清CEA水平与EGFR-TKI药物厄洛替尼治疗晚期非小细胞肺癌疗效的相关性。方法:对60例晚期非小细胞肺癌患者二线采用厄洛替尼进行治疗,并在接受治疗前进行血清CEA水平的检测,同时对患者的预后与患者的性别、年龄、分期、病理类型以及CEA水平等进行分析。以50μg/L为分界线,将患者分为高CEA水平组以及低CEA水平组。结果:对2组患者治疗疗效比较,高CEA水平组患者其有效率为50.0%、稳定为33.3%、进展为16.7%;而低CEA水平组患者分别为14.6%、43.8%以及41.7%,2组患者治疗疗效差异有统计学意义(P＜0．05)。对患者进行生存分析结果提示,高CEA水平患者其经过厄洛替尼治疗后有更长的无疾病进展时间以及生存时间(P＜0．05)。结论:血清CEA水平可作为评估厄洛替尼治疗晚期非小细胞肺癌的疗效以及预后的生化指标。     

厄洛替尼一线治疗晚期非小细胞肺癌的研究进展

世界范围内,肺癌是导致癌症患者死亡的第1位病因,其中非小细胞肺癌（NSLCLC）占新诊断肺癌的80％以上。大多数患者在诊断时即为不可切除,根治性治疗后复发的患者也很常见。目前标准的两药含铂化疗方案治疗晚期非小细胞肺癌的疗效不尽人意,随机临床试验显示中位生存期不到10个月,很少有患者能活过2年。尽管许多临床研究试图将不同的化疗方案联合运用到治疗中,     

厄洛替尼治疗老年晚期非小细胞肺癌的临床观察

目的 研究厄洛替尼治疗老年晚期非小细胞肺癌的临床疗效.方法 选取90例老年晚期非小细胞肺癌患者为研究对象,给予所有患者口服厄洛替尼150 mg/d,直至患者病情发生进展或出现不良反应,分析临床疗效及毒副作用.结果 近期临床总有效率(OR)为33.33％,疾病控制率(DCR)为84.44％.患者无进展生存期(PFS)平均为6.1个月,总生存期(OS)平均为12.2个月.女性患者的近期有效率高于男性患者,年龄≤65岁的患者近期有效率高于年龄＞ 65岁的患者,吸烟或有吸烟史患者的近期有效率低于不吸烟患者,腺癌患者的近期有效率高于非腺癌患者,但差异均无统计学意义(P＞0.05);有皮疹患者的近期有效率明显高于无皮疹症状患者.患者临床常见的不良反应多为轻度或中度的呕吐、腹泻及皮疹等症状.结论 厄洛替尼治疗老年晚期非小细胞肺癌的临床效果明显,药物毒副作用小,患者易耐受,值得临床推广应用.     

厄洛替尼二次治疗晚期非小细胞肺癌患者的临床分析

背景与目的:厄洛替尼治疗表皮生长因子受体突变的晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)患者疗效显著,但几乎所有患者最终都会出现耐药而导致病情进展。本研究旨在评估二次使用厄洛替尼治疗晚期NSCLC患者的疗效及安全性。方法:回顾性分析了福建省肿瘤医院46例既往厄洛替尼治疗有临床获益的晚期NSCLC患者,经其它药物治疗失败后二次给予厄洛替尼150 mg口服,每日1次,持续用药直至肿瘤进展或出现不可耐受的不良反应,对其临床特点、治疗效果及生存情况进行分析。结果:厄洛替尼二次治疗的客观有效率为28.3%,疾病控制率为60.9%,症状改善率为45.7%,中位无进展生存期为3.6个月,中位总生存期为7.3个月,1年生存率为8.7%。厄洛替尼停用≥6个月的患者中位无进展生存期显著长于停用<6个月的患者(P=0.002)。ECOG评分0~2分患者中位总生存期显著长于ECOG评分>2分的患者(P=0.038)。最常见的不良反应为皮疹和腹泻。结论:初次使用厄洛替尼有临床获益的晚期NSCLC患者,二次使用厄洛替尼仍有可能延长患者的生存时间。     

Phosphorylated EGFR expression may predicts outcome of EGFR-TKIs therapy for the advanced NSCLC patients with wild-type EGFR

ABSTRACT: BACKGROUND: EGFR mutation is a strong predictive factor of EGFR-TKIs therapy. However, at least 10% of patients with EGFR wild-type are responsive to TKIs, suggesting that other determinants of outcome besides EGFR mutation might exist. We hypothesized that activation of phosphorylated EGFR could be a potential predictive biomarker to EGFR-TKIs treatment among patients in wild-type EGFR. METHOD: Total of 205 stage IIIb and IV NSCLC patients, tissue samples of whom were available for molecular analysis, were enrolled in this study. The phosphorylation of EGFR at tyrosine 1068 (pTyr1068) and 1173 (pTyr1173) were assessed by immunohistochemistry, and EGFR mutations were detected by denaturing high performance liquid chromatograph (DHPLC). RESULTS: Among 205 patients assessable for EGFR mutation and phosphorylation analysis, 92 (44.9%) were EGFR mutant and 165 patients (57.6%) had pTyr1173 expression. Superior progression-free survival (PFS) was seen after EGFR-TKIs therapy in patients with pTyr1068 expression compared to pTyr1068 negative ones (median PFS 7.0 months vs. 1.2 months, P<0.001). Inversely, patients with pTyr1173 had a shorter PFS (4.8 months VS. 7.7 months, P=0.016). In subgroup of patients with wild-type EGFR, pTyr1068 expression positive ones had a significantly prolonged PFS (4.2 months vs.1.2 months P<0.001) compared with those without pTyr1068 expression.Sixteen patients with both wild-type EGFR and pTyr1068 who responded to EGFR-TKIs had median PFS of 15.6 months (95%CI: 7.28-23.9). CONCLUSION: pTyr1068 may be a predictive biomarker for screening the population for clinical response to EGFR-TKIs treatment; especially for patients with wild-type EGFR.     

吉非替尼、厄洛替尼与埃克替尼治疗EGFR基因敏感突变晚期NSCLC患者的疗效观察

目的:观察吉非替尼、厄洛替尼与埃克替尼在EGFR基因敏感突变晚期非小细胞肺癌(NSCLC)患者一线治疗中的疗效差异。方法:收集2013年5月—2014年12月间在我院接受治疗的76例EGFR基因突变的晚期NSCLC患者,随机分为三组,A组接受吉非替尼治疗,250 mg,1次/d,空腹口服;B组接受厄洛替尼治疗,150 mg,1次/d,餐前1 h口服;C组接受埃克替尼治疗,125 mg,3次/d,评价疗效及安全性。结果:吉非替尼组、厄洛替尼组和埃克替尼组的客观有效率（ORR）分别为26.9%、34.6%和45.8%;疾病控制率（DCR）分别为61.5%、73.0%和79.2%。三组之间的有效率和疾病控制率差异无统计学意义(P＞0.05）。三组的无进展生存时间（PFS）分别为9.5个月、10个月和9.5个月;19号外显子缺失突变型患者中,三组的PFS分别为8.5个月、12个月和9个月;21号外显子L858R错义突变型患者中,PFS分别为9.5个月、8.5个月和7个月,三组之间无统计学差异(P＞0.05）。结论:吉非替尼、厄洛替尼与埃克替尼治疗EGFR基因突变的晚期NSCLC疗效相似,但在19号外显子缺失突变型患者中,厄洛替尼略显优势。     

阿帕替尼治疗EGFR野生型晚期非小细胞肺癌的疗效及安全性

目的:探索阿帕替尼治疗表皮生长因子受体(epidermal growthfactor receptor,EGFR)野生型晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)的疗效及安全性.方法:回顾性纳入62例本中心符合纳入标准的、接受阿帕替尼单药治疗晚期NSCLC患者,分析其疗效及不良...     

Erlotinib 'dosing-to-rash': a phase II intrapatient dose escalation and pharmacologic study of erlotinib in previously treated advanced non-small cell lung cancer

Background:

To evaluate the anticancer activity of erlotinib in patients with previously treated, advanced non-small cell lung cancer (NSCLC) whose dose is increased to that associated with a maximal level of tolerable skin toxicity (i.e., target rash (TR)); to characterise the pharmacokinetics (PK) and pharmacodynamics (PD) of higher doses of erlotinib.

Methods:

Patients initially received erlotinib 150 mg per day. The dose was successively increased in each patient to that associated with a TR. Anticancer activity was evaluated. Plasma, skin, and hair were sampled for PK and PD studies.

Results:

Erlotinib dose escalation to 200–475 mg per day was feasible in 38 (90%) of 42 patients. Twenty-four (57%) patients developed a TR, but 19 (79%) did so at 150 mg per day. Five (12%) patients, all of whom developed a TR, had a partial response. Median progression-free survival (PFS) was 2.3 months (95% CI: 1.61, 4.14); median PFS was 3.5 months and 1.9 months, respectively, for patients who did and did not experience a TR (hazard ratio, 0.51; P=0.051). Neither rash severity nor response correlated with erlotinib exposure.

Conclusion:

Intrapatient dose escalation of erlotinib does not appreciably increase the propensity to experience a maximal level of tolerable skin toxicity, or appear to increase the anticancer activity of erlotinib in NSCLC.     

Intercalated chemotherapy and erlotinib for advanced NSCLC: high proportion of complete remissions and prolonged progression-free survival among patients with EGFR activating mutations

Background

Pharmaco-dynamic separation of cytotoxic and targeted drugs might avoid their mutual antagonistic effect in the treatment of advanced non-small cell lung cancer (NSCLC).

Patients and methods.

Eligible patients were treatment-naive with stage IIIB or IV NSCLC. In addition, inclusion was limited to never-smokers or light smokers or, after 2010, to patients with activating epidermal growth-factor receptor (EGFR) mutations. Treatment started with 3-weekly cycles of gemcitabine and cisplatin on days 1, 2 and 4 and erlotinib on days 5 to 15. After 4 to 6 cycles, patients continued with erlotinib maintenance.

Results

Fifty-three patients were recruited into the trial: 24 prior to 2010 (of whom 9 were later found to be positive for EGFR mutations), and 29 EGFR mutation-positive patients recruited later. Unfavourable prognostic factors included stage IV disease (51 patients - 96%), performance status 2–3 (11 patients - 21%) and brain metastases (15 patients -28%). Grade 4 toxicity included 2 cases of neutropenia and 4 thrombo-embolic events. The 15 EGFR negative patients had 33% objective response rate, median progression-free survival (PFS) 6.0 months and median survival 7.6 months. Among 38 EGFR positive patients, complete response (CR) or partial response (PR) were seen in 16 (42.1%) and 17 (44.7%) cases, respectively. PET-CT scanning was performed in 30 patients and confirmed CR and PR in 16 (53.3%) and 9 (30.0%) cases, respectively. Median PFS for EGFR mutated patients was 21.2 months and median survival was 32.5 months.

Conclusions

While patients with EGFR negative tumors do not benefit from addition of erlotinib, the intercalated schedule appears most promising for those with EGFR activating mutations.     

氩氦刀联合放疗治疗晚期EGFR野生型非小细胞肺癌合并慢性阻塞性肺疾病患者的临床观察

目的:探讨氩氦刀联合放疗一线治疗晚期EGFR野生型非小细胞肺癌合并慢性阻塞性肺疾病(COPD)患者的近期疗效.方法:对26例EGFR野生型合并COPD的肺癌患者在一线化疗的基础上对胸部不同部位病灶合理利用放疗和氩氦刀联合治疗.对中央病灶或纵隔转移淋巴结实行姑息性三维适行放疗(3DCRT),而对周围肺部病灶行经皮穿刺氩氦刀冷冻消融治疗,观察其近期治疗效果和不良反应.结果:26例患者经过联合治疗后,一线有效率达到42.31％,疾病控制率(DCR)为80.77％,近期疗效并不弱于PS评分好的晚期肺癌患者.所有患者的不良反应均为Ⅰ到Ⅱ级,经处理后都能完成整个治疗过程.结论:对于晚期EGFR野生型非小细胞肺癌合并慢性阻塞性肺疾病患者,设计个体化方案,通过合理利用化疗、放疗、氩氦刀能取得较好的疗效.     

Bevacizumab plus erlotinib in Chinese patients with untreated,EGFR-mutated,advanced NSCLC (ARTEMIS-CTONG1509): A multicenter phase 3 study

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Comparison of gefitinib and erlotinib in advanced NSCLC and the effect of EGFR mutations

Introduction

Erlotinib and gefitinib are tyrosine kinase (TK) inhibitors of epidermal growth factor receptor (EGFR) that are effective in treating non-small cell lung cancer (NSCLC). This study aimed to compare their clinical uses and the influence of EGFR mutation.

Methods

The usages of erlotinib and gefitinib in advanced NSCLC were analyzed. Clinical data and EGFR mutational status of tumors were collected.

Results

Seven hundred and sixteen (716) patients received gefitinib (n = 440) or erlotinib (n = 276) for stage IIIb or IV NSCLC. Erlotinib was prescribed more frequently than gefitinib in males (58.2% vs. 41.8%, p < 0.001), smokers (60.5% vs. 39.5%, p < 0.001), and non-adenocarcinoma (70.6% vs. 29.4%, p < 0.001). Of the 716 study patients, 327 underwent testing for EGFR mutations (170 with mutant EGFR and 157 with wild-type EGFR). Adenocarcinoma in patients with mutant EGFR and non-smoker status in patients with wild-type EGFR were associated with better overall survival after TK inhibitor treatment. In both patient groups with mutant EGFR or wild-type EGFR, the effectiveness of gefitinib and erlotinib, including drug response or overall survival, were not different.

Conclusions

Our study revealed the obvious disparity in drug selection between erlotinib and gefitinib in clinical practice. Type of TK inhibitors did not influence treatment outcomes in patients with EGFR mutation or wild-type EGFR.     

局限性晚期非小细胞肺癌手术治疗的共识和争论

局限性广泛期NSCLC手术预后较差,近年相关研究颇多,在发展过程中必然存在共识、也会有争论。共识:手术能否全部切除、T3胸壁侵犯者预后较中央型T3为好。T3伴否肺门淋巴结转移预后显然不同,纵隔淋巴结转移N2和预后密切相关,其中淋巴结转移数、部位、侵及淋巴结外膜和年生存率密切相关。术前诱导治疗可改善Ⅲ期长期年生存率,尚需扩大病例数及多中心随机研究,T4N3Ⅲb期NSCLC预后差,切除率低。争论:临床分期方法不同影响结果,如N2影像分期不如纵隔镜,但前者为无创伤性检查。术后放疗能降低复发,未见有益于生存。肺上沟瘤术前放疗并发症高。30％患者有胸内淋巴结跳站转移,手术时应切开纵隔仔细搜寻送检各站淋巴结。pN2作全肺切除死亡率高,不见得有益。隆突切除不适用于伴N1、N2患者。胸膜癌性积液原则上属非手术疾病。