厄洛替尼挽救治疗吉非替尼治疗失败的晚期非小细胞肺癌的疗效

目的评价厄洛替尼作为挽救方案治疗吉非替尼治疗失败的晚期非小细胞肺癌(NSCLC)的疗效及安全性。方法回顾性分析我院收治的96例采用厄洛替尼挽救治疗吉非替尼治疗后进展或复发的NSCLC患者,随访1年,观察有效率(RR)、疾病控制率(DCR)、疾病无进展生存时间(PFS)及不良反应。结果其中CR0例,PR 10例(10.42%),SD 50例(52.08%),PD 36例(37.50%),RR为10.42%,DCR为62.50%。吉非替尼治疗失败后给予化疗,进展后再给予厄洛替尼治疗者PFS为4.4个月;未间隔化疗直接给予厄洛替尼治疗者PFS为3.3个月。SD组以厄洛替尼治疗,RR、PFS分别为23.96%(23/96)、3.2个月,DCR为88.54%(85/96),非SD组DCR为52.08%(50/96),前者DCR显著高于后者(P<0.05)。结论厄洛替尼挽救治疗吉非替尼治疗失败的NSCLC具有较好的临床获益率,尤其是可提高吉非替尼治疗失败的疾病控制率,效果显著,不良反应轻微。     

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。     

厄洛替尼在老年非小细胞肺癌脑转移治疗中的临床应用

目的探讨厄洛替尼(TKI)在老年非小细胞肺癌(NSCLC)脑转移治疗中的临床疗效与毒副作用。方法 32例临床确诊的老年非小细胞肺癌脑转移患者,应用厄洛替尼150 mg/d,直到病情进展。观察近期临床疗效和毒副作用。结果厄洛替尼治疗非小细胞肺癌脑转移完全缓解(CR)3例,部分缓解(PR)10例,稳定(SD)10例,进展(PD)9例,中位总生存率(OS)为10.3个月,临床缓解率90.6%,临床受益率(CR+PR+SD)71.9%,1年生存率为35.9%,2年生存率为18.6%,性别、病理类型和吸烟史与临床受益率有一定关联。厄洛替尼毒副作用主要是皮疹、腹泻、座疮、皮肤干燥等。结论上皮生长因子细胞增殖和信号传导受体(EGFR)突变、腺癌、女性、不吸烟的老年肺癌患者选用厄罗替尼临床获益较多,野生型和未检测突变的老年肺癌患者选用厄罗替尼也可部分受益,具有较好的临床疗效,毒副反应轻,可耐受。     

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。     

吉非替尼治疗晚期复发非小细胞肺癌

目的 评价吉非替尼治疗晚期复发非小细胞肺癌的临床价值.方法 48例经病理确诊既往化疗失败的NSCLC患者,吉非替尼250mg口服,每日1次,连续用药至肿瘤进展或发生不可耐受的毒副作用.结果 48例均可评价疗效,总RR为22.9%,腺癌患者的有效率显著高于非腺癌患者(P=0.024),不吸烟者的有效率显著高于吸烟者(P=0.011),疾病控制率77.1%,中位PFS为4个月,中位生存期为8.9个月,常见的毒副作用是皮疹和腹泻.结论 吉非替尼治疗既往化疗失败的晚期非小细胞肺癌,具有较好的疗效和安全性.     

厄洛替尼与培美曲塞治疗晚期非小细胞肺癌疗效的间接比较

目的：根据临床研究文献,采用间接比较的方法综合评价厄洛替尼与培美曲塞治疗晚期非小细胞肺癌的临床疗效。方法：计算机检索国内外公开发表的关于厄洛替尼或培美曲塞治疗晚期非小细胞肺癌的中英文文献,采RevMan5.0和ITC软件对纳入的研究进行间接比较。结果：共纳入7项吉非替尼vs厄洛替尼和7项吉非替尼 vs培美曲塞的文献进行间接比较。厄洛替尼与培美曲塞治疗晚期非小细胞肺癌的有效率和疾病控制率的RR值分别为1.11(P=0.40)、1.12(P=0.69)。结论：厄洛替尼和培美曲塞治疗晚期非小细胞肺癌的疗效无显著性差异,但二者的临床有效性尚需要更多高质量的大规模随机对照研究来进行证实。     

厄洛替尼治疗晚期非小细胞肺癌临床观察

目的观察厄洛替尼治疗晚期非小细胞肺癌的疗效。方法采用厄洛替尼治疗晚期非小细胞肺癌12例,按WHO实体瘤客观疗效标准评价疗效。结果CR0例,PR3例,SD6例,PD3例,有效率为25％,疾病控制率为75％。不良反应为皮疹和腹泻。结论疗效满意,机体能够耐受,安全可靠。     

放疗联合厄洛替尼治疗非小细胞肺癌的临床研究

目的观察放疗联合厄洛替尼治疗晚期非小细胞肺癌的近期疗效及临床获益效果。方法 40例晚期非小细胞肺癌患者均有组织病理学或细胞学诊断及可评价的客观指标。20例（联合组）采用厄洛替尼150mg/d口服治疗,同时给予同步放射治疗,常规放射治疗6000cGY/30d。20例（放疗组）采用单纯放射治疗,常规放射治疗6000cGY/30d。结果 40例全部完成治疗,联合组完全缓解（CR）4例,部分缓解（PR）10例,总有效率（CR＋PR）为70%,1年和3年生存率和中位生存期联合组分别为72%,38%和26.3个月。单纯放疗组CR1例,PR7例,总有效率（CR＋PR）40%,1年和3年生存率和中位生存期分别为56%,22%和16.6个月。2组疗效差异有统计学意义（P〈0.05）。结论放疗联合厄洛替尼是治疗晚期非小细胞肺癌患者的有效方案,能缓解症状,改善生活质量,延长生存期。     

厄洛替尼治疗晚期非小细胞肺癌临床研究

目的分析在晚期非小细胞肺癌的临床治疗中应用厄洛替尼的临床疗效、毒副反应等。方法从2009年4月~2013年4月期间收治的晚期非小细胞肺癌患者中选取30例作为研究对象,并给予患者应用厄洛替尼进行治疗,若患者出现病变进展、无法耐受的毒副反应,则终止治疗,期间观察患者在应用该药物后的疗效、毒副反应等。结果研究发现,30例晚期非小细胞肺癌患者,11例患者疾病进展(PD),12例患者疾病稳定(SD),7例患者部分缓解(PR),0例患者完全缓解(CR),治疗有效例数为7例,占总人数的23.33%。在毒副反应方面,患者在用药后,主要有恶心呕吐、腹泻、皮肤瘙痒以及皮疹等,程度均不严重,通过相应的治疗后得到缓解。结论在晚期非小细胞肺癌患者的临床治疗中应用厄洛替尼,有明显的疗效,且毒副反应较为轻微。     

EGFR-216 G/T基因多态性与厄洛替尼治疗晚期非小细胞肺癌患者临床疗效的关系

目的:探索表皮生长因子受体(EGFR)-216 G/T基因多态性与厄洛替尼治疗晚期非小细胞肺癌(NSCLC)临床疗效间的关系。方法:利用Sequenom MassArrayiPLEX GOLD系统对135例晚期NSCLC患者外周血EGFR基因启动子-216 G/T(rs712829)基因多态性进行检测。分析EGFR-216G/T位点的基因多态性与客观缓解率(RR)、疾病控制率(DCR)和无进展生存时间(PFS)的关系。结果:EGFR-216G/T基因频率为GG 81.5%(112/135),GT 11.9%(16/135),TT 6.6%(9/135)。EGFR-216G/T GG和GT+TT基因型RR之间差异有统计学意义(18.2%vs.48.0%,P=0.002);EGFR-216G/T GG和GT+TT基因型DCR之间差异有统计学意义(53.6%vs.76.0%,P=0.042);GG和GT+TT基因型之间中位PFS差异有统计学意义(3.95个月vs.6.80个月,P=0.038)。结论:EGFR-216G/T多态性与厄洛替尼治疗晚期NSCLC患者的疗效有相关性。EGFR-216G/T多态性可用于预测厄洛替尼治疗NSCLC患者的疗效。     

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。     

Erlotinib in non-small-cell lung cancer

Epidermal growth factor receptor (EGFR) plays an essential role in normal cell growth and differentiation, and is involved in tumour proliferation and survival. EGFR overexpression is a common feature in solid malignancies, including non-small-cell lung cancer (NSCLC), and is associated with poor clinical prognosis. Erlotinib is a small-molecule inhibitor of EGFR tyrosine kinase, showing a significant improvement in median survival, quality of life and related symptoms in an unselected population of advanced NSCLC patients in the second- or third-line setting. Erlotinib is well tolerated (with common toxicities including rash and diarrhoea) when administered at a standard oral daily dose of 150 mg. Further investigations are ongoing to contribute to our understanding of the role of erlotinib in NSCLC treatment.     

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.     

非小细胞肺癌患者的新选择—厄洛替尼（特罗凯）

目的：综述了厄洛替尼的靶向作用、药动学、临床研究及不良反应皮疹与疗效的关系。方法：通过查阅国内外文献总结了厄洛替尼的单药试验及合并用药试验，并对研究结果进行分析。结果：单药试验表明厄洛替尼能够显著延长患者的生存期并提高生存质量：合并用药试验未发现显著性优势。其不良反应皮疹的发生及程度与患者的生存期及疾病缓解率存在显著性关系。结论：厄洛替尼能够显著延长晚期或转移型非小细胞肺癌患者的生存期，其不良反应皮疹与疗效的相关性仍需进一步研究。     

Erlotinib in non-small-cell lung cancer

Epidermal growth factor receptor (EGFR) plays an essential role in normal cell growth and differentiation, and is involved in tumour proliferation and survival. EGFR overexpression is a common feature in solid malignancies, including non-small-cell lung cancer (NSCLC), and is associated with poor clinical prognosis. Erlotinib is a small-molecule inhibitor of EGFR tyrosine kinase, showing a significant improvement in median survival, quality of life and related symptoms in an unselected population of advanced NSCLC patients in the second- or third-line setting. Erlotinib is well tolerated (with common toxicities including rash and diarrhoea) when administered at a standard oral daily dose of 150 mg. Further investigations are ongoing to contribute to our understanding of the role of erlotinib in NSCLC treatment.     

厄洛替尼一线治疗老年非小细胞肺癌脑转移7例疗效观察

目的探讨厄洛替尼一线治疗老年非小细胞肺癌(NSCLC)脑转移的疗效与安全性。方法对7例确诊的老年非小细胞肺癌患者,应用厄洛替尼150 mg·d-1,直到病情进展。结果厄洛替尼治疗老年非小细胞肺癌脑转移的ORR为57.1%,DCR为85.7%,中位OS为12月,1年生存率为42.9%,2年生存率为28.6%。结论厄洛替尼一线治疗老年NSCLC脑转移,具有较好的临床疗效,毒副反应轻,可耐受。     

Erlotinib in non-small cell lung cancer: a review

Erlotinib (Tarceva?, OSI-774; Pfizer, Inc.) is an orally-active, targeted inhibitor of the epidermal growth factor receptor (EGFR/HER1), which is part of a key regulatory pathway in cancer. Patients with advanced, incurable non-small cell lung cancer (NSCLC) may derive a clinical benefit from first- and second-line chemotherapy, but third-line treatment with available cytotoxic agents is not effective. Remarkably, EGFR/HER1 antagonists have demonstrated activity as second- and even third-line treatment for this disease. Erlotinib is the first of this novel class of drug to demonstrate a statistically significant and clinically relevant difference in overall survival, progression free survival and time to disease related symptoms (cough, pain, shortness of breath) compared with treatment with best supportive care in patients who have failed standard first- or second-line chemotherapy. This paper reviews the pharmacology, preclinical and clinical data to support the use of erlotinib in NSCLC.     

Erlotinib in non-small cell lung cancer: a review

Erlotinib (Tarceva, OSI-774; Pfizer, Inc.) is an orally-active, targeted inhibitor of the epidermal growth factor receptor (EGFR/HER1), which is part of a key regulatory pathway in cancer. Patients with advanced, incurable non-small cell lung cancer (NSCLC) may derive a clinical benefit from first- and second-line chemotherapy, but third-line treatment with available cytotoxic agents is not effective. Remarkably, EGFR/HER1 antagonists have demonstrated activity as second- and even third-line treatment for this disease. Erlotinib is the first of this novel class of drug to demonstrate a statistically significant and clinically relevant difference in overall survival, progression free survival and time to disease related symptoms (cough, pain, shortness of breath) compared with treatment with best supportive care in patients who have failed standard first- or second-line chemotherapy. This paper reviews the pharmacology, preclinical and clinical data to support the use of erlotinib in NSCLC.     

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.