厄洛替尼二线单药治疗肺癌36例疗效观察

目的观察厄洛替尼(特罗凯)单药治疗晚期肺癌的疗效及不良反应。方法 36例晚期非小细胞肺癌一线化疗失败患者口服厄洛替尼150mg/d至肿瘤进展或出现不可耐受的不良反应,评价其近期疗效、不良反应及生活质量、无进展生存期及总生存期。结果 36例患者中PR 8例(22.22%),SD 15例(41.66%),PD 13例(36.11%),有效率(CR+PR)为22.22%;疾病控制率(CR+PR+SD)为72.22%。肿瘤进展时间为2～11个月,中位无进展生存期为5.9个月;中位生存期为11.6个月。主要的不良反应为皮疹、皮肤瘙痒、恶心、腹泻,多为Ⅰ～Ⅱ度,对症处理后可缓解。结论厄洛替尼单药二线治疗非小细胞肺癌疗效好、不良反应轻。     

1例盐酸厄洛替尼致不良反应的药学监护

盐酸厄洛替尼是一种口服高效表皮生长因子受体酪氨酸激酶（EGFR）选择性抑制药,通过影响细胞内磷酸化过程来抑制信号通路的传导,进而抑制肿瘤细胞的扩散及增殖来达到抗肿瘤的目[2]。大型临床研究证实,厄洛替尼靶向治疗非小细胞肺癌（NSCLC）晚期,能显著延长患者的生存期。而对于老年及身体状态评价差的患者,厄洛替尼单药不失为一线治疗的新选择[3]。本文讨论了1例NSCLC晚期患者单药使用盐酸厄洛替尼靶向治疗过程中出现严重药物疹及其他不良反应的药学监护。     

非小细胞肺癌靶向治疗新药——厄洛替尼

厄洛替尼是一种口服、高选择性、可逆的表皮生长因子受体(EGFR)酪氨酸激酶(TK)抑制剂,它通过抑制EGFR-TK的自磷酸化反应,抑制信号转导,从而达到抑制肿瘤生长作用。一项Ⅲ期安慰剂对照临床研究结果表明,厄洛替尼每日口服150 mg单药治疗,可显著延长晚期复发性非小细胞肺癌(NSCLC)病人的生存期、延缓疾病进展和症状恶化,且耐受性较好,最常见的不良反应为皮疹和腹泻。本文对厄洛替尼的药动学和药效学特性、临床疗效和药物相互作用以及难治性晚期NSCLC病人的耐受性等作一综述。     

厄洛替尼不良反应的干预及护理

目的通过对服用厄洛替尼的患者进行干预及护理,降低该药不良反应的发生。方法对24例口服厄洛替尼的非小细胞肺癌患者的临床资料进行回顾性分析,总结对其不良反应的干预及护理措施。结果24例患者中14例出现不同程度的皮疹,8例腹泻,2例无特殊不良反应。除2例重症皮疹停药外,其余继续口服厄洛替尼治疗。结论通过对厄洛替尼所致的不良反应进行干预及护理,能提高患者的生存质量,使厄洛替尼发挥更好的临床疗效。     

厄洛替尼上市后不良反应的文献回顾性分析

目的探讨厄洛替尼自2007年在中国上市后所致不良反应的种类及特点,以指导临床合理用药。方法检索2007～2012年中国期刊全文数据库和中华医学会全文数据库内收录的521例厄洛替尼不良反应,进行统计学分析。结果521例患者中,60岁以上男性有合并用药史者,在服药后14d内易出现不良反应,主要是皮疹、腹泻、肝功能异常。间质性肺病是严重不良反应。结论临床医师、药师应重视厄洛替尼的不良反应,坚持合理用药。     

小分子靶向药物治疗非小细胞肺癌的不良事件研究进展

目的:综述近年关于厄洛替尼和吉非替尼单用或合并用药研究中导致停药的主要不良反应及其用药的危险因素。方法:查阅、综述、分析近几年关于厄罗替尼和吉非替尼单用或合并用药在非小细胞肺癌治疗方面的研究文献。结果与结论:厄洛替尼和吉非替尼具有耐受性好且不良反应少等特点,但该类药物相关的不良事件依然应当受到关注。     

厄洛替尼治疗晚期非小细胞肺癌的疗效观察

目的：研究厄洛替尼对晚期化疗失败的非小细胞肺癌（NSCLC）患者的疗效。方法：30例晚期NSCLC患者，口服厄洛替尼150mg·d^-1，直到病情进展或者因不良反应不能耐受为止。观察疗效，不良反应及疗效与，临床特征之间的关系。结果：31）例患者中7例部分缓解，16例稳定，7例进展，总缓解率为23．3％，疾病控制率为76．7％。Fisher’精确检验提示在肿瘤缓解率方面，年龄小于60岁者优于60岁以上患者，在肿瘤控制率方面，有皮疹患者优于无皮疹患者。结论：厄洛替尼治疗晚期化疗失败的NSCLC有一定疗效，不良反应少。     

厄洛替尼单药一线治疗老年晚期非小细胞肺癌32例临床观察

目的探讨厄洛替尼单药一线治疗老年晚期非小细胞肺癌临床疗效及毒副反应,为老年患者治疗提供新的方向。方法收集本院肿瘤内科经组织学或细胞学证实的老年晚期非小细胞肺癌并自愿接受单药厄洛替尼治疗的患者32例,观察近期疗效及毒副反应,并通过随访观察无进展生存期(PFS)、总生存期(OS)。结果完全缓解为0,部分缓解为43.8%,疾病稳定为34.4%,疾病进展为21.9%。有效率为43.8%。PFS为4.28个月,OS为10.55个月。鳞癌患者的PFS和OS明显低于腺癌患者(P<0.01),吸烟患者的PFS和OS明显低于不吸烟的患者(P<0.01)。主要毒副反应为皮疹,腹泻,厌食,乏力,且以Ⅰ、Ⅱ度为主。结论厄洛替尼单药一线治疗老年晚期非小细胞肺癌安全有效。     

厄洛替尼致不良反应的文献分析

目的：探讨和分析厄洛替尼不良反应的发生规律及特点。方法登陆中国知网CNKI.NET、万方数据知识服务平台、维普中文期刊全文数据库及超星数字图书馆收录的180例厄洛替尼不良反应报道文献,进行统计学分析。结果180例不良反应报道中,以皮疹、腹泻、间质性肺病为严重不良反应。结论临床医师、药师应重视厄洛替尼的不良反应,坚持合理用药。     

化疗期间序贯应用厄洛替尼治疗晚期非小细胞肺癌的临床疗效观察

目的 观察化疗期间序贯给予厄洛替尼对晚期非小细胞肺癌(NSCLC)的疗效和不良反应.方法 58例NSCLC晚期患者化疗期间序贯给予厄洛替尼150 mg/ d,给药至疾病进展或不良反应无法耐受.采用实体瘤的疗效评价标准评价疗效.结果 58例患者中客观有效率为27.6%(16/58),疾病控制率为80.0%(47/58).主要的不良反应有皮疹、腹泻和血液系统毒性.主要的不良反应有皮疹、腹泻和血液系统毒性,皮疹多为炎性脓疱疹,常分布于颜面部、颈部、躯干和四肢等.36例出现皮疹,占62.1%.血液系统毒性主要表现为白细胞和血小板减少.结论 化疗期间序贯给予厄洛替尼治疗晚期NSCLC的近期疗效较好,不良反应耐受性好,远期疗效需进一步观察.     

厄洛替尼联合贝伐珠单抗治疗EGFR突变晚期非小细胞肺癌患者的有效性和安全性的Meta分析

目的：系统评价未经化疗的新确诊或复发的EGFR突变晚期非小细胞肺癌患者使用厄洛替尼或联合贝伐珠单抗治疗的有效性和安全性。方法：检索PubMed及其他数据库中截至2020年10月24日所有相关的随机对照临床试验。结果：最终纳入3项符合条件的随机对照临床研究,共计464例患者。Meta分析结果显示,厄洛替尼联合贝伐珠单抗化疗显著延长了未经化疗的新确诊或复发EGFR突变晚期非小细胞肺癌患者的无进展生存期（P<0.000 1,HR=0.62,95% CI：0.49~0.78）。然而,联合化疗并没有明显改善该患者人群的客观缓解率（P=0.19,RR=1.08,95% CI：0.96~1.22）。联合化疗组中3级及以上级别的不良事件发生率明显高于对照组（P<0.000 01,RR=1.89,95% CI：1.62~2.19）。结论：厄洛替尼联合贝伐珠单抗治疗可能会显著延长未经化疗的新确诊或复发的EGFR突变晚期非小细胞肺癌患者群体的无进展生存期,但是无法显著提高客观缓解率。同时,联合治疗方式可能会增加3级及以上不良反应的发生。这些发现可能需要更多相关临床研究进行验证。     

Bevacizumab and erlotinib versus bevacizumab for colorectal cancer treatment: systematic review and meta-analysis

Background Improving the survival of patients diagnosed with metastatic colorectal cancer requires the use of chemotherapy to be managed with minimum adverse effects. Randomized control trials (RCTs) have shown promising results with a combination of bevacizumab and erlotinib to block two important tumor growth pathways, namely vascular endothelial growth factor and epidermal growth factor receptor. Aim of the Review We aimed to examine the efficacy and safety of the combination of bevacizumab and erlotinib with bevacizumab alone in the maintenance treatment of metastatic colorectal cancer, by examining PFS, OS, overall response rate (ORR), and toxicity. This study performed a systematic review meta-analysis using existing randomized clinical trial. Methods Randomized controlled trials were systematically reviewed from PubMed, Cochrane library, SCOPUS, CRD, and Google scholar databases. After evaluating the quality of studies through the Cochrane checklist, data of the relevant studies were extracted. This meta-analysis included outcomes of overall survival, progression-free survival of the disease through the hazard ratio, and the upper and lower confidence intervals for the third and fourth degree side effects of relative risk. To perform the meta-analysis for both types of survival, two fixed and random effect models were used. Results A total of three trials, providing data of 682 patients who received maintenance treatment, were included in this meta-analysis. Conclusion The combination of bevacizumab and erlotinib significantly increased the overall survival compared to using bevacizumab alone [HR?=?0.78, 95% CI 0.66–0.93]. This combination, effectively increased progression-free survival [HR?=?0.81, 95% CI 0.7–0.93] too. The side effects of diarrhea and grade III rash were more frequent in the group administered bevacizumab plus erlotinib. The combination of bevacizumab and erlotinib, in the maintenance treatment of metastatic colorectal cancer, significantly improved the overall survival and progression-free survival of patients, and the resulting side effects were easily treatable.

     

Epidermal growth factor receptor tyrosine kinase inhibitors in previously treated advanced non-small-cell lung cancer with wild-type EGFR

Introduction: While epidermal growth factor receptor (EGFR) – tyrosine kinase inhibitors (TKIs) lead to longer progression-free survival (PFS) when compared with conventional chemotherapy in non-small-cell lung cancer (NSCLC) harboring activating EGFR mutations, the role of EGFR-TKI remains unclear in EGFR-wild-type (WT) NSCLC.

Areas covered: This article reviews selected data from randomized trials regarding the use of TKIs in EGFR-WT NSCLC. Nine randomized phase III trials have compared EGFR-TKI with chemotherapy in NSCLC patients in a second or later line setting. Two of these trials, TAILOR and DELTA, which were designed to investigate treatment benefits according to EGFR genotype, demonstrated that docetaxel chemotherapy displayed significantly better in progression-free survival (PFS) when compared with the EGFR-TKI erlotinib. Biomarkers to predict clinical benefits of the drug against EGFR WT tumor, and the efficacy of combination regimens using erlotinib or single-use afatinib against tumors are also covered in this article.

Expert opinion: Considering the modest benefits of erlotinib for EGFR-WT tumors, future studies are warranted, including the exploration of useful biomarkers and new treatment strategies for EGFT-TKI use, as well as the development of more sensitive EGFR mutation tests.     

Erlotinib: a new therapeutic approach for non-small cell lung cancer

Although treatment with cytotoxic agents has produced modest survival improvement in patients with stage III and IV non-small cell lung cancer (NSCLC), it appears that a plateau has been reached with currently available chemotherapeutic regimens. Increasing knowledge regarding the properties of malignant neoplasms has identified a number of potential therapeutic targets. The epidermal growth factor receptor (EGFR) is one of these targets. Preclinical models have revealed that tumour growth can be inhibited by monoclonal antibodies directed against EGFR and EGFR-specific tyrosine kinase inhibitors. Erlotinib (Tarceva?; OSI Pharmaceuticals, Genentech and Roche), a quinazoline derivative with good oral absorption, is one of several EGFR tyrosine kinases that has been studied in clinical trials. In a Phase I study, mild diarrhoea and mild rash were the most common toxicities. At a dose of 200 mg/day, diarrhoea was the dose-limiting toxicity. The observation that EGFR overexpression is relatively common in NSCLC led to a Phase II trial of erlotinib at the maximum-tolerated dose (150 mg/day) in previously treated NSCLC patients. Erlotinib produced a 12% response rate and there was no apparent relationship between response and tumour EGFR levels. More recent reports suggest that patients who develop a rash have higher responses. Based on its single agent activity, erlotinib has been evaluated in two Phase III trials which compared erlotinib plus chemotherapy to chemotherapy alone in previously untreated NSCLC patients. Erlotinib has also been compared to placebo in a Phase III trial which was limited to advanced stage NSCLC patients whose disease had progressed after two previous chemotherapy regimens. The optimum use of erlotinib in NSCLC will be determined by the results of the completed and future Phase III trials.     

Erlotinib: a new therapeutic approach for non-small cell lung cancer

Although treatment with cytotoxic agents has produced modest survival improvement in patients with stage III and IV non-small cell lung cancer (NSCLC), it appears that a plateau has been reached with currently available chemotherapeutic regimens. Increasing knowledge regarding the properties of malignant neoplasms has identified a number of potential therapeutic targets. The epidermal growth factor receptor (EGFR) is one of these targets. Preclinical models have revealed that tumour growth can be inhibited by monoclonal antibodies directed against EGFR and EGFR-specific tyrosine kinase inhibitors. Erlotinib (Tarceva trade mark; OSI Pharmaceuticals, Genentech and Roche), a quinazoline derivative with good oral absorption, is one of several EGFR tyrosine kinases that has been studied in clinical trials. In a Phase I study, mild diarrhoea and mild rash were the most common toxicities. At a dose of 200 mg/day, diarrhoea was the dose-limiting toxicity. The observation that EGFR overexpression is relatively common in NSCLC led to a Phase II trial of erlotinib at the maximum-tolerated dose (150 mg/day) in previously treated NSCLC patients. Erlotinib produced a 12% response rate and there was no apparent relationship between response and tumour EGFR levels. More recent reports suggest that patients who develop a rash have higher responses. Based on its single agent activity, erlotinib has been evaluated in two Phase III trials which compared erlotinib plus chemotherapy to chemotherapy alone in previously untreated NSCLC patients. Erlotinib has also been compared to placebo in a Phase III trial which was limited to advanced stage NSCLC patients whose disease had progressed after two previous chemotherapy regimens. The optimum use of erlotinib in NSCLC will be determined by the results of the completed and future Phase III trials.     

Reviewing the safety of erlotinib in non-small cell lung cancer

Importance of the field: Erlotinib, a potent inhibitor of EGFR activity, is approved as a monotherapy for the treatment of advanced NSCLC and in combination with gemcitabine for advanced pancreatic cancer. The oral administration and manageable toxicity of erlotinib, along with its similar efficacy to chemotherapy, make it an important option as either maintenance therapy or in second-/third-line for patients with NSCLC who have previously received first-line chemotherapy. It is also an emerging option in other treatment settings in NSCLC.

Areas covered in this review: This review summarizes safety data from major clinical trials of erlotinib in patients with advanced NSCLC, as well as post-marketing data obtained in the 5 years since this drug was first approved.

What the reader will gain: An understanding of the common toxicities expected with erlotinib in patients with advanced NSCLC.

Take home message: Erlotinib is a well-tolerated treatment option for patients with advanced NSCLC. The main adverse events of rash and diarrhea are typically mild or moderate in severity, and rarely lead to treatment withdrawal. When necessary, rash and diarrhea can be easily managed prophylactically, by active intervention or through dose reduction.     

A review of erlotinib and its clinical use

Erlotinib is an orally available, reversible tyrosine kinase inhibitor of the epidermal growth factor receptor. Encouraging activity as a single agent and in combination with other targeted agents has been demonstrated in Phase II trials in many tumour types. Erlotinib has an established role in the treatment of advanced, refractory non-small cell lung cancer-based on a pivotal trial demonstrating a survival advantage over best supportive care. In a Phase III trial, the addition of erlotinib to gemcitabine improved survival in advanced pancreatic cancer. The toxicity profile of erlotinib includes diarrhoea and rash, with no haematological side effects. Predictive factors for response include the presence of a rash, epidermal growth factor receptor expression and mutation status. This article reviews the current clinical status of erlotinib.     

全脑放疗联合靶向治疗与同步放、化疗治疗非小细胞肺癌脑转移的临床疗效

目的 对比分析全脑放疗联合靶向治疗与同步放、化疗治疗非小细胞肺癌(NSCLC)脑转移的临床疗效及安全性.方法选取NSCLC脑转移病人56例作为研究的对象,经随机数字表法将之分为联合组与放化疗组,联合组病人采取全脑放疗联合靶向药物治疗,放化疗组采取全脑放疗以及同步化疗治疗.对病人进行为期2年的随访,比较两组病人治疗6个月后的临床疗效,并观察病人治疗期间并发症的发生情况以及随访期间的生存情况.结果联合组的脑转移病灶、总体评价的治疗有效率(RR)、疾病控制率(DCR)均显著高于放化疗组(P<0.05);联合组骨髓抑制、消化道反应的发生率均显著低于放化疗组,而皮疹脱屑的发病率则高于放化疗组(P<0.05);联合组1年生存率显著高于放化疗组,且平均生存时间较放化疗组更长(P<0.05);治疗结束后,联合组生存质量上升者显著多于放化疗组,而生存质量下降者则显著少于放化疗组(P<0.05).结论全脑放疗联合靶向治疗应用于NSCLC脑转移病人具有较好的疗效,能够减少不良反应,延长病人的生存时间.     

厄洛替尼治疗晚期非小细胞肺癌的疗效及安全性研究

目的厄洛替尼是治疗非小细胞肺癌的靶向药物,多项国内外研究已证明该药可延长非小细胞肺癌(non-small cell lung cancer,NSCLC)患者的生存。本研究回顾性总结了厄洛替尼在非选择NSCLC人群中的应用,旨在探讨厄洛替尼治疗晚期非小细胞肺癌的远期疗效及安全性。方法回顾分析本院2006年3月至2009年7月之间接受化疗后应用厄洛替尼治疗化疗失败的晚期NSCLC患者,口服150 mg/d厄洛替尼直至疾病进展,观察疗效、生存时间和副反应。结果共有36例患者入组。36例患者中PR 22.2%(8/36),SD 50.0%(18/36),PD 27.8%(10/36),CR=O,DCR(CR+PR+SD)72.2%;PFS为5.8个月。其中腺癌与非腺癌、无吸烟者与吸烟者的疗效差异无统计学意义,但是生存曲线提示腺癌比非腺癌患者(7.6个月vs 1.0个月,P=0.037)、无吸烟比吸烟患者(11.1个月vs 4.6个月,P=0.025)具有更长的PFS,差异有统计学意义;性别因素未能影响疗效或PFS。毒副作用主要为为轻度皮疹、腹泻、转氨酶升高。结论厄洛替尼治疗晚期非小细胞肺癌有效,对腺癌和非吸烟人群有一定优势,且耐受性良好,是治疗晚期非小细胞肺癌患者的一个新的选择。