吉非替尼与厄洛替尼二线治疗晚期非小细胞肺癌的对比研究

目的:比较表皮生长因子受体酪氨酸激酶抑制剂吉非替尼与厄洛替尼治疗一线化疗失败的晚期非小细胞肺癌(NSCLC)的疗效性及安全性.方法:83例一线治疗失败的NSCLC患者,接受厄洛替尼治疗的患者42例,接受吉非替尼治疗的患者41例,两组患者基本情况大致平衡,并评价两组患者的疗效、无进展生存时间(PFS)、中位生存时间(MST)和毒副反应.结果:比较两组患者中位PFS,中位OS等指标,差异均无统计学意义(P＞0.05).厄洛替尼组较吉非替尼组患者药物毒副反应的发生率较高.两组患者肿瘤病理类型比较有统计学意义(P＜0.05),厄洛替尼组中肺鳞癌患者的生存期较吉非替尼组明显延长.结论:在标准一线化疗失败的晚期NSCLC患者中,吉非替尼与厄洛替尼的总体疗效相似,对于肺鳞癌患者厄洛替尼能明显延长患者的生存期,但副反应的发生率高于吉非替尼组患者.     

厄洛替尼联合DC\CIK治疗晚期非小细胞肺癌28例临床护理

目的:探讨肿瘤靶向治疗药物厄洛替尼联合树突状细胞(DC)\细胞因子诱导的杀伤细胞(CIK)治疗晚期非小细胞肺癌(NSCLC)的临床效果及护理方法。方法:将56例晚期非小细胞肺癌患者随机分为观察组和对照组各28例,两组给予相同的护理方法,对照组给予厄洛替尼治疗,观察组给予厄洛替尼联合DC\CIK治疗;比较两组治疗效果。结果:两组均有不同程度的不良反应,均顺利完成治疗;两组无进展生存期(PFS)比较差异有统计学意义(P0.05)。结论:对晚期NSCLC患者给予厄洛替尼联合DC\CIK维持治疗及有效护理,可明显减轻患者不良反应,从而提高治疗效果。     

厄洛替尼治疗晚期非小细胞肺癌致间质性肺病的护理

厄洛替尼是一种选择性表皮生长因子酪氨酸激酶抑制剂,其主要用于既往至少一种化疗方案失败的局部晚期或转移性非小细胞肺癌(NSCLC)病人的治疗,其作为二线或三线治疗方案,已被证实能显著延长各种非小细胞肺癌病人的生存期,从而广泛应用于临床。     

靶向药物厄洛替尼的研究进展

厄洛替尼是一种新型且高效的小分子1型人表皮生长因子受体/表皮生长因子受体（HER1/EG-FR）酪氨酸激酶抑制剂,有EGFR过度表达的非小细胞肺癌,厄洛替尼已作为其二线、三线用药.近几年来关于厄洛替尼在其他肿瘤方面研究越来越多,且其治疗作用的研究也取得了一定的成效,因此厄洛替尼有可能成为多种肿瘤的靶向药物.本文就厄洛替尼的药理学特性、作用机制、不良反应、临床研究及应用等方面研究进展综述如下.     

厄洛替尼致重度皮疹1例的护理体会

<正>厄洛替尼(Erlotinib hydrochloride tablets)(商品名特罗凯)是一种口服表皮生长因子受体酪氨酸激酶抑制剂,在美国国立综合癌症网络(NCCN)肺癌指南中被列为治疗晚期非小细胞肺癌表皮生长因子受体(EGFR)突变患者的推荐治疗选择[1]。临床中最常见的不良反应为皮疹、腹泻,发生率分别为76%和55%,严重的皮疹(≥3度)发生率13%[2]。虽国内外已有口服厄洛替尼致皮     

酪氨酸激酶抑制剂治疗非小细胞肺癌的护理体会

目的探讨酪氨酸激酶抑制剂(厄洛替尼和吉非替尼)治疗非小细胞肺癌的疗效并对其护理体会进行总结。方法对46例晚期非小细胞肺癌患者应用厄洛替尼150mg/d或吉非替尼250mg/d口服,观察病情进展或出现不可耐受的不良反应。对患者用药期间出现的不良反应加强护理,提高患者治疗的依从性。结果在46例患者中完全缓解(CR)3例,部分缓解(PR)22例,疾病稳定(SD)11例,总有效率为78.3%。其中,发生皮疹39例(84.8%),胃肠道反应12例(26.1%),口腔溃疡1例(2.2%),肝功能异常2例(4.3%)。结论厄洛替尼和吉非替尼治疗非小细胞肺癌给药方法简便易行,患者耐受性良好且疗效确切,及时进行相应的护理干预和对症处理可以预防和减轻不良反应,有效改善患者的生活质量。     

厄洛替尼联合全脑放疗治疗非小细胞肺癌脑转移

探讨厄洛替尼联合全脑放疗治疗非小细胞肺癌脑转移的疗效。70例患者均为本院2014年4月~2016年5月期间收治的非小细胞肺癌脑转移患者,按照双色球分组法将其分为两组。单纯接受全脑放疗的35例患者归入对照组,观察组35例在对照组基础上联合使用厄洛替尼治疗。治疗结束后,观察两组患者的病灶控制情况,并统计两组患者治疗过程中不良反应发生情况。观察组患者病灶控制率62.86%,显著高于对照组48.57%,差异有统计学意义(P0.05)。治疗过程中,观察组总计发生5例不良反应,对照组总计发生6例不良反应,两组比较无明显差异(P0.05)。针对非小细胞肺癌脑转移的患者,可在全脑放疗基础上联合使用表皮生长因子受体酪氨酸激酶抑制剂厄洛替尼治疗,不但能显著控制病灶转移,且不良反应较少,值得推广。     

厄洛替尼治疗晚期非小细胞肺癌的不良反应与护理

目的:探讨厄洛替尼治疗晚期非小细胞肺癌的不良反应及护理措施。方法:将收治的晚期非小细胞肺癌患者96例随机分为观察组A、观察组B和对照组各32例,对照组给予常规化疗,观察组A给予厄洛替尼治疗,观察组B给予厄洛替尼联合化疗治疗,三组均针对不良反应给予精心护理,比较三组不良反应发生率。结果:观察组A和观察组B腹泻发生率均低于对照组(P0.05),观察组B和对照组肝功能异常发病率均高于观察组A(P0.05),观察组B和对照组其他不良反应发生率均高于观察组A(P0.05)。结论:厄洛替尼治疗晚期非小细胞肺癌不良反应轻微,主要为皮疹和腹泻,通过及时停药或对症护理后症状消失,能够更好地提高患者生存质量。     

EGFR-TKIs影响老年晚期非小细胞肺癌患者T淋巴细胞亚群的研究

目的:研究老年晚期非小细胞肺癌(NSCLC)患者表皮生长因子酪氨酸激酶抑制剂(EGFR-TKIs)治疗前后外周血T淋巴细胞亚群的变化及其临床意义。方法:检测45例老年晚期NSCLC初治患者治疗前的外周血T细胞亚群,与非老年晚期NSCLC患者及健康老年人进行比较,并对老年晚期NSCLC患者EGFR-TKIs治疗前后、不同用药(吉非替尼组、厄洛替尼组)的T细胞亚群指标进行对比。结果:老年晚期NSCLC组与老年健康组对比,CD3+、CD4+、NK、CD4+/CD8+明显下降,CD25+明显升高,具有统计学差异(P<0.05);与中青年晚期NSCLC组比较,CD4+、CD4+/CD8+下降更明显(P<0.05);老年晚期NSCLC患者在EGFR-TKIs治疗后比治疗前CD3+、CD4+、CD4+/CD8+明显上升(P<0.05),CD25+明显下降(P<0.05);与吉非替尼组相比,厄洛替尼组CD4+/CD8+上升幅度更明显(P<0.05),CD25+下降更显著(P<0.05)。结论:老年晚期NSCLC患者存在着明显的免疫抑制,EGFR-TKIs对患者的免疫功能有明显改善作用,厄洛替尼比吉非替尼作用更突出。     

一例口服特罗凯诱发严重痛风反应患者的护理

特罗凯（厄洛替尼）是一种分子靶向抗肿瘤药物，作为表皮生长因子受体（EGFR）酪氨酸激酶抑制剂的代表性药物，可通过对肿瘤细胞EGFR结构的特异性结合阻断细胞信号通路，抑制肿瘤细胞增殖并促其凋亡。在晚期非小细胞肺癌（NSCLC）的治疗中疗效确切，占有重要地位，     

Indirect Treatment Comparisons of Ibrutinib Versus Physician’s Choice and Idelalisib Plus Ofatumumab in Patients With Previously Treated Chronic Lymphocytic Leukemia

Purpose

Treatment options for patients with relapsed or refractory chronic lymphocytic leukemia (R/R CLL) are limited. Until recently, few effective treatment options existed, and even with the advent of new agents, studies evaluating comparative efficacy are scarce. In the Ibrutinib Versus Ofatumumab in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia (RESONATE) Phase III study, ibrutinib, an oral, once-a-day, first-in-class covalent Bruton tyrosine kinase inhibitor, improved progression-free survival (PFS) and overall survival (OS) compared with ofatumumab (PFS hazard ratio [HR] = 0.106 and OS HR = 0.369 [adjusted for crossover] at a median of 16 months’ follow-up). We sought to establish the relative efficacy of ibrutinib versus other treatment options for patients with R/R CLL using indirect comparison methods.

Erlotinib: small-molecule targeted therapy in the treatment of non-small-cell lung cancer

BACKGROUND: Erlotinib is an oral tyrosine kinase inhibitor, targeting the human epidermal receptor type 1/ epidermal growth factor receptor, recently approved by the US Food and Drug Administration (FDA) for the treatment of patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC) after the failure of more than 1 or 2 previous chemotherapeutic regimens. OBJECTIVE: The purpose of this article is to summarize the development, pharmacology, pharmacokinetics, efficacy, and adverse effects of erlotinib. METHODS: A literature search was conducted with the MEDLINE and EMBASE (1999-2005) databases using the search terms non-small-cell lung cancer, erlotinib, and epidermal growth factor receptor inhibitor. Abstracts from the American Society of Clinical Oncology and documents submitted to the FDA also were reviewed. RESULTS: BR.21, a randomized, placebo-controlled, multinational Phase III trial demonstrated clinically and statistically improved overall survival in patients with advanced or metastatic NSCLC treated with erlotinib versus placebo as second-line therapy. The erlotinib group had a median survival of 6.7 months versus a median survival of 4.7 months in the placebo group (P < 0.001). The toxicity profile of erlotinib was moderately benign, with the most commonly documented adverse events requiring dose reductions including skin rash (12%) and diarrhea (5%). Interstitial lung disease and relative fatalities were reported infrequently (0.8%) in patients receiving erlotinib. Two randomized, placebo-controlled, multicenter Phase III trials conducted in patients with locally advanced and metastatic NSCLC showed no clinical benefit with first-line administration of erlotinib plus concurrent platinum-based chemotherapy. CONCLUSIONS: For patients with NSCLC in whom more than 1 or 2 previous chemotherapeutic regimens have failed, erlotinib is an effective therapy with significant overall survival benefits. The use of erlotinib as first-line therapy in combination with platinum-based chemotherapeutic regimens, however, has failed to demonstrate efficacy in the treatment of NSCLC.     

盐酸安罗替尼治疗晚期非小细胞肺癌的临床观察

目的:探讨盐酸安罗替尼治疗晚期非小细胞肺癌(non-small lung cancer,NSCLC)的临床疗效及不良反应。方法:回顾性分析2017年6月至2019年1月徐州医科大学附属医院收治的三线治疗及以上的晚期NSCLC,应用盐酸安罗替尼治疗的45例患者的临床资料,综合评价患者的疗效和无进展生存期(progression-free survival,PFS)以及不良反应情况。结果:共纳入45例患者,将患者分为安罗替尼单药组(24例)与安罗替尼联合用药组(21例),其中联合白蛋白结合型紫杉醇化疗17例,联合纳武单抗免疫治疗4例。在45例患者中,部分缓解(partial remission,PR)占4.4%(2/45),疾病稳定(stable disease,SD)占88.9%(40/45),疾病进展(progressive disease,PD)占6.7%(3/45),客观有效率(objective response rate,ORR)为4.4%,疾病控制率(disease control rate,DCR)为93.3%。45例患者的中位PFS为3.70个月,经log-rank检验结果显示不同治疗方案差异有统计学意义(P<0.05)。其中单药组患者中位PFS为3.30个月,联合用药组患者中位PFS为5.30个月,联合用药组PFS优于单药组。不良反应主要包括乏力、高血压、食欲不振、手足综合征等,其中3级不良事件包括高血压、手足综合征及骨髓抑制,未发现4级及以上的不良事件。结论:盐酸安罗替尼在三线治疗及以上的晚期NSCLC的治疗中,具有较好的疾病控制及生存获益,且不良反应相对可控。     

Lung cancer]

Since the late 1980s, lung cancer incidence in men has declined in Germany whereas in women there is still a rise. There is no approved screening program for lung cancer up to now and results from randomized trials like the National Lung Screening Trial are eagerly awaited. In stage II and IIIA non-small cell lung cancer (NSCLC), several positive trials have demonstrated the advantage of adjuvant chemotherapy which is now an established modality to improve cure rates. Epidermal growth factor receptor (EGFR) is commonly overexpressed in NSCLC. Erlotinib, an EGFR tyrosine kinase inhibitor, has been approved for relapsed advanced-stage NSCLC. Bevacizumab is a monoclonal antibody against vascular endothelial growth factor, a primary mediator of angiogenesis that is commonly overexpressed in solid tumors including lung cancer. Bevacizumab, in combination with chemotherapy, has demonstrated improved outcomes in advanced NSCLC and is now approved for selected patients with advanced-stage NSCLC. Patient selection for therapeutic use of bevacizumab is crucial to optimize safety. Ongoing trials explore multitargeted agents such as sorafenib, sunitinib, and vandetanib.     

血小板与淋巴细胞比值对非小细胞肺癌预后评估的Meta分析

目的 探讨血小板与淋巴细胞比值(PLR)对非小细胞肺癌(NSCLC)患者预后的评估作用。方法 检索各中英文数据库建库至2017年10月公开发表的关于PLR与非小细胞肺癌预后关系研究的中英文文献,根据纳入与排除标准对文献进行筛选、资料提取和质量评价,筛选后的文献数据用ReviewManager5.3软件进行统计分析,将风险比(HR)与95%可信区间(95%CI)进行合并,并进行各研究间的异质性检验,根据异质性的大小决定采用固定效应模型(P>0.10,I²<50%)或随机效应模型(P<0.10,I²≥50%)进行分析。采用漏斗图进行发表偏倚分析。结果 纳入12篇符合标准的文献,共计3 720例NSCLC患者。PLR与术后总生存率(OS)的关系采用随机模型进行分析(I²=60%,P<0.01),Meta分析结果显示,高PLR组的OS明显低于低PLR组,风险比(HR=1.81),95%可信区间(95%CI:1.47～2.24,P<0.001)。进行亚组分析结果显示,在种族、治疗方法、样本量和PLR截断值等方面,高PLR组的OS明显低于低PLR组(P值均<0.05)。PLR与无病生存率/无进展生存时间(DFS/PFS)的关系采用固定效应模型进行分析(I²=21%,P=0.27),Meta分析结果显示,高PLR组的DFS/PFS明显低于低PLR组(HR=1.42,95%CI:1.22～1.65,P<0.001)。结论PLR升高的NSCLC患者预后较差,PLR可作为评估NSCLC患者预后的指标。     

Meta-Analysis to Assess the Efficacy and Toxicity of Docetaxel-Based Doublet Compared with Docetaxel Alone for Patients with Advanced NSCLC who Failed First-Line Treatment

PurposeThe benefit of docetaxel-based therapy in the second-line treatment of advanced non–small cell lung cancer (NSCLC) is still unclear. The goal of this meta-analysis was to assess the efficacy and toxicity of docetaxel-based doublet compared with docetaxel alone for patients with advanced NSCLC who failed to improve with first-line treatment.MethodsSeveral databases were searched, including PubMed, Embase, and the Cochrane databases. The end points were overall survival, progression-free survival (PFS), objective response rate, disease control rate, and grade 3 or 4 adverse events. Data were extracted from the studies by 2 independent reviewers. The meta-analysis was performed by using Review Manager version 5.2. The pooled hazard ratio (HR) or odds ratio (OR) and 95% CIs were calculated by using fixed or random effects models depending on the heterogeneity of the included trials.FindingsTwelve eligible trials involving 2680 patients were identified. The intention-to-treatment analysis found that docetaxel-based therapy significantly improved overall survival (HR, 0.89 [95% CI, 0.83–0.96]; P < 0.01), PFS (HR, 0.79 [95% CI, 0.71–0.89]; P < 0.01), objective response rate (OR, 1.73 [95% CI, 1.37–2.18; P < 0.01), and disease control rate (OR, 1.30 [95% CI, 1.09–1.55]; P < 0.01). In addition, a subgroup analysis based on type of combined drug showed that there were significant improvement in PFS and overall survival in combining docetaxel with targeted therapy. In addition, a higher incidence of grade 3 or 4 diarrhea and thrombocytopenia was observed in docetaxel-based doublet therapy.ImplicationsBased on the available evidence, docetaxel-based doublet therapy seems superior to docetaxel monotherapy as a second-line treatment for advanced NSCLC. More studies should focus on combining docetaxel with targeted therapy to identify patients who will most likely benefit from the appropriate combination targeted therapy.     

Systematic review and meta-analysis of Chinese herbal medicine as adjuvant treatment in advanced non-small cell lung cancer patients

IntroductionWhether combining Chinese herbal medicines (CHMs) and chemotherapy to treat patients with advanced non-small-cell lung cancer (NSCLC) has clinical benefits has yet to be confirmed. A meta-analysis was performed to address the efficacy of CHM in patients with advanced NSCLC.MethodsSeven databases, including PubMed, MEDLINE, Cochrane Library, Embase, CINAHL Plus with Full Text (EBSCO), WANFANG DATA and the Chinese National Knowledge Infrastructure (CNKI), were systematically searched for available literature through March10, 2020. A meta-analysis was conducted to generate combined risk ratios(RRs) with 95 % confidence intervals (CIs) for objective response rates (ORRs), disease control rates (DCRs), and 1-year overall survival (OS) rates, and a random-effects model was used to estimate the standardized mean differences (SMDs) with 95 % CI for quality or life (QOL), median survival time (mST) and progression-free survival (PFS).ResultsReports of 14 randomized controlled trials involving 1451 patients were included in the analysis. Among them, 739 patients received CHMs, and 712 patients received chemotherapy alone. The ORR (RR = 1.37, 95 % CI [1.20‐1.58], p = .000), DCR (RR = 1.13, 95 % CI [1.07‐1.21], p = 0.000), QOL (SMD = 1.47; 95 % CI [0.30–2.64]; p = 0.014), mST (SMD = 1.62; 95 % CI [1.15‐2.08];p = .000), and 1-year OS rate (RR = 1.24, 95 % CI [1.05‐1.47], p = 0.01) were higher in patients with NSCLC who received CHMs than in those who received only chemotherapy. However, the CHM group was not found to have a higher median PFS (SMD = 1.27, 95 % CI [-0.22‐2.78], p = .095) than the chemotherapy group. Publication bias for ORR and DCR was indicated by funnel plot. For the efficacy endpoint, no evidence of a lack of robustness was found, according to the sensitivity analysis. These results must be interpreted with caution due to differences in the designs of the trials and patients’ characteristics, and also due to the presence of missing data.ConclusionsOur study found that higher ORR, DCR, QOL, mST and 1-year OS rate were associated with CHM use as an adjuvant to chemotherapy. Although these results require further confirmation, CHMs apparently have potential therapeutic value for patients with advanced NSCLC.     

Pemetrexed as the first-line therapy for Chinese patients with advanced non-squamous non-small-cell lung cancer

Non-small cell lung cancer (NSCLC) represents the most common cause of cancer mortality worldwide and counts for the greatest number of deaths from lung cancer in both men and women over age 60. Pemetrexed is a multi-targeted anti-metabolite and has shown comparable activity for Caucasian patients with advanced NSCLC. In this single-center retrospective study, we analyzed the outcome in 75 Chinese non-squamous NSCLC patients treated with pemetrexed as first-line therapy and assessed its efficacy and tolerability. The overall response rate was 9.3% (7/75) with 7 partial response s and no complete response. There were 44 (58.7%) stable diseases and 24 progressive diseases (32.0%). The median progression-free survival (PFS) was 6.79 months (95% CI 5.69–7.90 months), and the median overall survival (OS) was 11.67 months (95% CI 9.98–13.36 months). Good performance status and negative smoke history predicted better PFS and OS. Most side effects were generally mild and well tolerated. Taken together, pemetrexed was safe and effective in Chinese patients with non-squamous NSCLC. Pemetrexed alone or in combination with other efficacious drugs may serve as first-line therapy for this disease.     

厄洛替尼治疗晚期非小细胞肺癌临床疗效影响因素分析

目的探讨厄洛替尼治疗晚期非小细胞肺癌临床疗效的影响因素。方法将208例晚期非小细胞肺癌按照中位无进展生存期分为两组,中位无进展生存期≥5个月者设为A组(101例),中位无进展生存期<5个月者设为B组(105例)。两组均给予厄洛替尼联合贝伐单抗治疗,观察直至疾病进展或者死亡。比较两组患者的一般资料,分析两组临床疗效影响因素。结果两组患者性别、年龄、吸烟史、病理分型、疾病分期比较差异有统计学意义(P<0.01),A组患者男性比例、年龄、吸烟史比例显著B组(P<0.01)。吸烟史及病理分型是厄洛替尼治疗晚期非小细胞肺癌患者临床疗效的影响因素(P<0.05)。结论吸烟史及病理分型是厄洛替尼治疗晚期非小细胞肺癌患者临床疗效的影响因素,无吸烟史及腺癌患者无进展生存期更久。     

The T790M "gatekeeper" mutation in EGFR mediates resistance to low concentrations of an irreversible EGFR inhibitor

Patients with non-small cell lung cancer (NSCLC) harboring activating mutations in the epidermal growth factor receptor (EGFR) kinase domain tend to respond well to the tyrosine kinase inhibitors, gefitinib and erlotinib. However, following clinical response, these patients typically relapse within a year of treatment. In many cases, resistance is caused by an acquired secondary EGFR kinase domain mutation, T790M. In vitro studies have shown that a new class of EGFR-irreversible inhibitors could overcome the resistance conferred by T790M. Clinical trials are under way to examine the efficacy of one of these inhibitors, HKI-272, in patients with NSCLC who initially responded to gefitinib/erlotinib and subsequently relapsed. To anticipate the possibility that patients who respond to irreversible inhibitors will develop secondary resistance to such inhibitors, as has been seen in other similar settings, we modeled acquired resistance to the dual EGFR/HER2-irreversible tyrosine kinase inhibitor HKI-272 in a NSCLC cell culture model. We found that HKI-272-resistant clones fall into two biochemical groups based on the retention of EGFR phosphorylation in the presence of the drug. Cells that retain phosphorylated EGFR have acquired the secondary mutation T790M. Moreover, HKI-272 can overcome T790M resistance only at suprapharmacologic concentrations. We further model mutations at EGFR C797 as a mechanism of resistance to irreversible EGFR inhibitors and show that although these mutants are resistant to the irreversible inhibitor, they retain erlotinib sensitivity. Our findings suggest that HKI-272 treatment at maximally tolerated dosing may lead to the emergence of T790M-mediated resistance, whereas treatment with a more potent irreversible inhibitor could yield a resistance mutation at EGFR C797.