吉非替尼的药理作用和临床应用概况

目的了解吉非替尼的药理作用与临床应用概况。方法查阅吉非替尼相关的国内外资料,并对其进行综述。结果吉非替尼单药或联合治疗晚期非小细胞肺癌疗效肯定,患者耐受性好。结论吉非替尼治疗表皮生长因子受体（EGFR）突变的非小细胞肺癌（NSCLC）患者有较好疗效。     

贝伐珠单抗联合吉非替尼治疗EGFR突变阳性晚期非小细胞肺癌的应用效果

目的探究在内皮生长因子受体(EGFR)突变阳性晚期非小细胞肺癌治疗中,吉非替尼与贝伐珠单抗联合应用效果和安全性。方法56例EGFR突变晚期非小细胞肺癌患者,以整群随机化方式分为单药组和联合组,每组28例。给予对照组患者吉非替尼给予,研究组患者吉非替尼联合贝伐珠单抗治疗。比较两组患者临床疗效、无进展生存时间,记录两组不良反应发生情况。结果联合组患者治疗客观缓解率89.29%高于单药组的64.29%;研究组患者无进展生存时间(18.0±0.6)个月长于对照组的(11.2±0.5)个月,差异均具有统计学意义(P<0.05)。联合组的不良反应主要为高血压(11例)和蛋白尿(12例),其中高血压和蛋白尿≥3级占比分别为18.2%(2/11)、8.3%(1/12),均在预期范围内,患者无明显自我感受,不影响生活质量。单药组皮疹发生率为57.1%(16/28)、腹泻发生率为35.7%(10/28),大多为1~2级。结论对EGFR突变阳性晚期非小细胞肺癌患者予以吉非替尼与贝伐珠单抗联合治疗,能延长患者的无进展生存时间,不良反应率均可耐受,安全性好。     

非替尼联合多西他赛对EGFR突变阳性晚期非小细胞肺癌患者呼吸功能和不良反应发生率的影响

目的:探讨吉非替尼联合多西他赛用于治疗表皮生长因子受体(EGFR)突变阳性晚期非小细胞肺癌的效果.方法:选择69例EGFR突变阳性晚期非小细胞肺癌患者将其分为对照组(n=35,多西他赛联合顺铂治疗)和观察组(n=34,吉非替尼联合多西他赛),比较两组患者临床疗效、不良反应发生情况.结果:观察组总有效率为70.58％,高于对照组(51.43％),疾病控制率为91.17％高于对照组(80.00％)(P<0.05);观察组不良反应发生率为11.76％低于对照组(31.43％)(P<0.05).结论:EGFR突变阳性晚期非小细胞肺癌患者应用吉非替尼联合多西他赛疗效显著、改善患者呼吸功能、减少不良反应发生率.     

吉非替尼联合化疗治疗晚期肺腺癌疗效观察

目的:观察吉非替尼联合化疗治疗晚期肺腺癌的疗效。方法:从2013年9月到2014年4月这8个月来本院就诊的50例晚期肺腺癌患者随机分为试验组和对照组。实验组接受吉非替尼联合化疗治疗,对照组仅接受吉非替尼治疗,对两组的治疗效果进行统计比较。结果:试验组的有效率为48%,对照组的有效率为64%,差异有统计学意义(P<0.05),仅服用吉非替尼的效果优于吉非替尼联合化疗的治疗方法。结论:吉非替尼联合化疗治疗晚期肺腺癌效果不明显,而且存在毒副反应。因此,吉非替尼不能与放化疗同时进行。     

吉非替尼一线治疗57例晚期非小细胞肺癌的疗效

目的分析观察吉非替尼一线对晚期非小细胞肺癌(NSCLC)患者的临床治疗效果与安全性。方法将我院57例晚期NSCLC患者随机的分成对照组和实验组两组,对照组29例,实验组28例。对照组采取安慰剂进行治疗,实验组采取吉非替尼进行一线治疗,分析对比两组患者所取得的疗效、安全性。结果实验组晚期NSCLC患者肺癌控制的有效率明显高于对照组,症状改善情况以及生存率均优于对照组,两组的差异十分明显,P<0.05。结论采取吉非替尼对晚期NSCLC患者进行一线治疗,所取得的效果较好,耐受性及有效性都比较不错,患者的病情能够得到一定控制,很少出现毒副作用。     

吉非替尼与GP方案治疗晚期非小细胞肺癌的疗效比较

目的:探讨吉非替尼与GP方案(吉西他滨联合顺铂)治疗晚期非小细胞肺癌(NSCLC)患者的疗效及安全性。方法:对96例晚期NSCLC患者的资料进行回顾性分析。其中48例应用吉非替尼治疗的患者设为观察组,48例应用GP方案的患者设为对照组,观察两组患者的治疗效果及不良反应。结果:观察组患者的疾病控制率明显优于对照组患者(P<0.05),患者胸痛、血痰、上腔静脉压迫综合征(SVCS)等症状迅速改善(P<0.05),生活质量明显提高(P<0.05),且不良反应较为轻微。结论:吉非替尼对不能耐受或拒绝采用化疗的晚期NSCLC患者疗效较好,可提高患者的生活质量,且不良反应轻微,具有较好的临床应用前景。     

吉非替尼联合化疗方案对EGFR突变晚期非小细胞肺癌患者疗效及CA19-9、CYFRA21-1、CEA表达的影响

目的 探究吉非替尼联合化疗方案对表皮生长因子(EGFR)突变晚期非小细胞肺癌患者的临床疗效。方法 80例EGFR突变晚期非小细胞肺癌患者,按照住院顺序分为对照组和观察组,各40例。对照组采用常规化疗方案治疗,观察组在对照组的基础上增加吉非替尼干预治疗。对比两组患者治疗前后卡氏功能状态评分(KPS)及肿瘤相关指标[糖类抗原CA19-9(CA19-9)、细胞角蛋白19片段(CYFRA21-1)及癌胚抗原(CEA)]。结果 治疗后,观察组KPS评分(87.73±5.55)分高于对照组的(83.54±5.65)分,差异有统计学意义(P<0.05)。治疗后,观察组CA19-9、CYFRA21-1及CEA水平分别为(32.17±5.66)U/ml、(2.77±0.88)ng/ml、(8.56±0.77)μg/L,均明显低于对照组的(35.54±5.21)U/ml、(3.34±0.98)ng/ml、(9.12±0.74)μg/L,差异有统计学意义(P<0.05)。结论 吉非替尼联合化疗方案可有效改善EGFR突变晚期非小细胞肺癌患者CA19-9、CYFRA21-1及CEA的表达,进而提高化...     

吉非替尼治疗非小细胞肺癌的临床研究进展

肺癌是肿瘤死亡的最常见原因,其中85%为非小细胞肺癌,且大多数患者有晚期的表现,患者5年的生成率仅为1%~5%,近年研发成功的酪氨酸激酶抑制剂,开启了肿瘤小分子靶向治疗的新时代,尤其是由阿斯利康公司研制并推出的吉非替尼,为晚期NSCLC患者又提供了一种有效的治疗药物。本文对吉非替尼治疗非小细胞肺癌的临床研究进展进行综述,其中包括全球范围内吉非替尼单药二线、一线和维持治疗,以及联合化疗治疗非小细胞肺癌的临床研究进展。     

吉非替尼联合吉西他滨和顺铂治疗晚期非小细胞肺癌的疗效

目的 ：观察吉非替尼联合吉西他滨和顺铂治疗晚期非小细胞肺癌的临床效果。方法 ：将98例晚期非小细胞肺癌患者随机分成对照组和研究组，各49例。对照组实施吉西他滨联合顺铂治疗，研究组在对照组基础上加用吉非替尼，对比两组临床疗效。结果 ：治疗后，研究组治疗总有效率，CD3+、CD4+水平和CD4+/CD8+比值均高于对照组；CD8+水平和不良反应发生率均低于对照组（P <0.05）。结论 ：对晚期非小细胞肺癌患者应用吉非替尼联合吉西他滨和顺铂治疗，能达到更好的疗效，还能改善患者免疫功能，且无明显不良反应，有一定的临床应用价值。     

吉非替尼联合顺铂、吉西他滨治疗晚期非小细胞肺癌的疗效及生存分析

摘要：目的:观察吉非替尼联合顺铂、吉西他滨治疗晚期非小细胞肺癌的疗效及生存相关因素。方法:171例Ⅲb～Ⅳ期非小细胞肺癌患者,接受顺铂化疗方案超过1个周期,接受吉非替尼联合顺铂和吉西他滨治疗直至疾病进展。选择171例同期未使用吉非替尼的患者按性别、年龄、吸烟与否、病理类型和分期进行匹配,作为对照组,比较两组患者的疗效、总生存期(OS)和总生存率、无进展生存期(PFS)、无进展生存率,以及药品不良反应。对吉非替尼组患者的疗效与PFS、总生存率的影响因素进行分析。结果:吉非替尼组患者客观缓解率为21.1%,疾病控制率为75.4%,均明显优于对照组(P<0.05或P<0.01);无进展生存率也优于对照组(P<0.05)。两组总生存率无明显差异(P>0.05)。性别和病理类型是PFS的独立危险因素(P<0.05),肿瘤病理类型和是否发生转移是总生存率的独立预后因素(P<0.05)。吉非替尼组患者的皮疹和腹泻发生率高于对照组(P<0.05)。结论:吉非替尼联合顺铂和吉西他滨治疗对Ⅲb～Ⅳ期非小细胞肺癌患者有效且安全。     

Gefitinib: current status in the treatment of non-small cell lung cancer

Gefitinib (Iressa) is a novel drug approved in 28 countries (as of June 2004), including Japan, the US, Canada and Australia as second- and third-line monotherapy for the treatment of locally advanced or metastatic non-small cell lung cancer refractory to prior chemotherapy. Gefitinib is an orally active, epidermal growth factor receptor (EGFR)-tyrosine kinase (EGFR-TK) reversible inhibitor which blocks EGFR phosphorylation and subsequent signal transduction pathways involved in proliferation, metastasis, angiogenesis and apoptosis inhibition. Recently, mutations in the TK domain of the EGFR have been identified in those patients with refractory non-small cell lung cancer who achieved dramatic tumor responses to gefitinib. Although the role of EGFR-TK mutation status in predicting other clinical benefits with gefitinib, i.e. disease stabilization and symptom improvement, is unclear, these findings, along with increasing knowledge of other potential biomarkers of response, are significant developments towards further optimizing the use of gefitinib. Gefitinib has favorable pharmacokinetic and pharmacodynamic properties and low toxicity. No dosage adjustment is required for patient age, body weight, gender, ethnicity or moderate to severe hepatic impairment due to liver metastases. Several clinical studies on gefitinib as monotherapy have demonstrated clinically significant symptom relief, tumor response and good tolerability after failure of chemotherapy-based treatment in non-small cell lung cancer. These studies led to gefitinib approval in many countries as a new therapeutic option for patients with advanced non-small cell lung cancer that failed prior chemotherapy. In contrast to the clinical benefit imparted by gefitinib as monotherapy in patients previously treated with chemotherapy, gefitinib in combination with standard platinum-based chemotherapy in chemonaive patients did not improve either survival or other clinical endpoints in non-small cell lung cancer. This review provides currently available data from clinical studies on gefitinib as monotherapy or in combination with platinum-containing chemotherapy.     

Gefitinib for non-small-cell lung cancer treatment

INTRODUCTION: Gefitinib is an EGFR tyrosine kinase inhibitor (EGFR-TKI) that demonstrated efficacy in patients with advanced non-small cell lung cancer (NSCLC) across therapy lines. In the first-line setting, recent randomized Phase III trials comparing EGFR-TKIs versus platinum-based doublets demonstrated that in patients harboring an activating EGFR mutation, gefitinib is superior to chemotherapy in terms of response rate, progression-free survival, toxicity profile and quality of life, with a marginal positive effect on survival. In order to choose the best treatment, a molecular characterization is now mandatory, as part of baseline diagnostic procedures. AREAS COVERED: All published data on gefitinib in lung cancer were analyzed using PubMed. The aim of this review is to summarize activity and safety data from major clinical trials of gefitinib in patients with advanced NSCLC. EXPERT OPINION: EGFR-TKIs including gefitinib are the best option we can offer today in patients with EGFR mutation, regardless of treatment line. Administration of gefitinib to patients with advanced NSCLC is usually well-tolerated and it also appears to be feasible in special populations characterized by a significantly poorer risk:benefit ratio with standard chemotherapy, like elderly patients and patients with poor performance status.     

吉非替尼的临床应用研究

吉非替尼为靶向性表皮生长因子受体(EGFR)酪氨酸激酶抑制剂,2005年批准进口中国用于治疗局部晚期及或转移性非小细胞肺癌(NSCLC),其疗效好且血液系统不良反应较少,最常见的不良反应为腹泻和皮肤反应.2015年7月13日,美国食品药品监督管理局批准吉非替尼用于转移性非小细胞肺癌靶向性表皮生长因子受体基因突变的患者.本文主要综述了其近年国内外的临床研究进展.     

Gefitinib for non-small-cell lung cancer treatment

Introduction: Gefitinib is an EGFR tyrosine kinase inhibitor (EGFR-TKI) that demonstrated efficacy in patients with advanced non-small cell lung cancer (NSCLC) across therapy lines. In the first-line setting, recent randomized Phase III trials comparing EGFR-TKIs versus platinum-based doublets demonstrated that in patients harboring an activating EGFR mutation, gefitinib is superior to chemotherapy in terms of response rate, progression-free survival, toxicity profile and quality of life, with a marginal positive effect on survival. In order to choose the best treatment, a molecular characterization is now mandatory, as part of baseline diagnostic procedures.

Areas covered: All published data on gefitinib in lung cancer were analyzed using PubMed. The aim of this review is to summarize activity and safety data from major clinical trials of gefitinib in patients with advanced NSCLC.

Expert opinion: EGFR-TKIs including gefitinib are the best option we can offer today in patients with EGFR mutation, regardless of treatment line. Administration of gefitinib to patients with advanced NSCLC is usually well-tolerated and it also appears to be feasible in special populations characterized by a significantly poorer risk:benefit ratio with standard chemotherapy, like elderly patients and patients with poor performance status.     

吉非替尼联合沙利度胺治疗非小细胞肺癌的临床疗效分析

目的 探讨吉非替尼联合沙利度胺对非小细胞肺癌患者近期疗效、生存质量及血清肿瘤标志物的影响。方法 选取淄博市第四人民医院2015年3月—2017年3月期间收治的晚期非小细胞肺癌患者98例,按照随机表法分为观察组49例与对照组49例。2组患者均采用DP化疗方案。对照组采用沙利度胺片,观察组在对照组基础上联用吉非替尼。2组均以28 d为1个周期,连续4个周期。比较2组近期疗效、生存质量改善情况,治疗前后血清肿瘤标志物水平变化,及不良反应发生情况。结果 观察组近期总有效率（75.51%）显著高于对照组（55.10%）（P<0.05）。观察组生存质量提高率（79.59%）显著高于对照组（59.18%）（P<0.05）。与治疗前比较,2组治疗后血清CA125、CEA和CYFRA21-1水平降低（P<0.05）;观察组治疗后血清CA125、CEA和CYFRA21-1水平低于对照组（P<0.05）。2组白细胞减少、血小板减少、恶心呕吐、乏力、肝功能损害及腹泻发生率比较无统计学意义。结论 吉非替尼联合沙利度胺对非小细胞肺癌患者近期疗效显著,可提高患者生存质量,降低血清CA125、CEA和CYFRA21-1水平。     

Gefitinib in non-small cell lung cancer

Gefitinib (Iressa^TM), an orally-active tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR), is the first approved molecular-targeted drug for the management of patients with advanced non-small cell lung cancer (NSCLC). Two Phase II trials (IDEAL [Iressa Dose Evaluation in Advanced Lung Cancer]-1 and -2), evaluated the efficacy of gefitinib in advanced NSCLC patients who received ≤ 2 (IDEAL1) or ≥ 2 (IDEAL2) previous chemotherapy regimens. The response rate and disease control rate in IDEAL1 and -2 was 18/12% and 54/42%, respectively. The median survival time and one-year survival rate in both studies were ~ 7 months and 30%, respectively. As gefitinib has demonstrated antitumour activity and an acceptable tolerability profile not typically associated with cytotoxic adverse events, such as hematological toxicities, combinations with cytotoxic drugs have been evaluated. Disappointingly, in chemotherapy-naive patients with advanced NSCLC, gefitinib 250 and 500 mg/day combined with platinum-based chemotherapy (gemcitabine/cisplatin or paclitaxel/carboplatin) did not produce prolonged survival, compared with chemotherapy alone in two large, randomised, placebo-controlled, multi-centre Phase III trials (INTACT [Iressa NSCLC Trial Assessing Combination Treatment]-1 and -2). Furthermore, in a recent randomised, placebo-controlled, Phase III trial (ISEL: IRESSA Survival Evaluation in Lung cancer), gefitinib failed to prolong survival compared with placebo in patients with advanced NSCLC who had failed one or more lines of chemotherapy. Subgroup analysis of ISEL suggested improved survival in patients of Asian origin and non-smokers. In addition, subset analyses of IDEAL and several retrospective studies have indicated that female gender, adenocarcinoma histology (especially bronchial alveolar carcinoma), non-smoker status and Asian ethnicity are factors which predict to response to gefitinib. Two types of somatic mutation clustered around the ATP binding pocket in the tyrosine kinase domain of the EGFR gene have been reported as possible surrogate biological markers for predicting response to gefitinib. Appropriate patient selection by clinical characteristics or genetical information is needed, both for future clinical trials of gefitinib and its routine use in the clinic among patients with advanced NSCLC.     

Gefitinib in non-small cell lung cancer

Gefitinib (Iressa), an orally-active tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR), is the first approved molecular-targeted drug for the management of patients with advanced non-small cell lung cancer (NSCLC). Two Phase II trials (IDEAL [Iressa Dose Evaluation in Advanced Lung Cancer]-1 and -2), evaluated the efficacy of gefitinib in advanced NSCLC patients who received < or = 2 (IDEAL1) or > or = 2 (IDEAL2) previous chemotherapy regimens. The response rate and disease control rate in IDEAL1 and -2 was 18/12% and 54/42%, respectively. The median survival time and one-year survival rate in both studies were approximately 7 months and 30%, respectively. As gefitinib has demonstrated antitumour activity and an acceptable tolerability profile not typically associated with cytotoxic adverse events, such as hematological toxicities, combinations with cytotoxic drugs have been evaluated. Disappointingly, in chemotherapy-naive patients with advanced NSCLC, gefitinib 250 and 500 mg/day combined with platinum-based chemotherapy (gemcitabine/cisplatin or paclitaxel/carboplatin) did not produce prolonged survival, compared with chemotherapy alone in two large, randomised, placebo-controlled, multi-centre Phase III trials (INTACT [Iressa NSCLC Trial Assessing Combination Treatment]-1 and -2). Furthermore, in a recent randomised, placebo-controlled, Phase III trial (ISEL: IRESSA Survival Evaluation in Lung cancer), gefitinib failed to prolong survival compared with placebo in patients with advanced NSCLC who had failed one or more lines of chemotherapy. Subgroup analysis of ISEL suggested improved survival in patients of Asian origin and non-smokers. In addition, subset analyses of IDEAL and several retrospective studies have indicated that female gender, adenocarcinoma histology (especially bronchial alveolar carcinoma), non-smoker status and Asian ethnicity are factors which predict to response to gefitinib. Two types of somatic mutation clustered around the ATP binding pocket in the tyrosine kinase domain of the EGFR gene have been reported as possible surrogate biological markers for predicting response to gefitinib. Appropriate patient selection by clinical characteristics or genetical information is needed, both for future clinical trials of gefitinib and its routine use in the clinic among patients with advanced NSCLC.     

吉非替尼治疗非小细胞肺癌的疗效与EGFR基因突变的关系

目的探讨吉非替尼治疗晚期非小细胞肺癌(NSCLC)的疗效与表皮生长因子受体(EGFR)基因突变的关系。方法选择36例Ⅲb期或Ⅳ期经铂类治疗方案无效的NSCLC患者,根据有无EGFR基因突变分为有EGFR基因突变组(A组,11例)与无EGFR基因突变组(B组,25例),均予以吉非替尼治疗,分析其疗效与EGFR基因突变的关系。结果 A组吉非替尼治疗有效率优于B组(81.8%vs.16.0%)(P<0.05)。结论 EGFR基因突变的检测可作为吉非替尼治疗NSCLC疗效的一个预测指标。     

Optimal management of patients with non-small cell lung cancer and epidermal growth factor receptor mutations

In recent years, the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), gefitinib and erlotinib, which have promising activity and a favourable toxicity profile, have been used in the management of advanced non-small cell lung cancer (NSCLC). The knowledge that EGFR-activating mutations confer sensitivity to EGFR TKIs has led to the design and analysis of phase II and III studies of gefitinib or erlotinib treatment in various clinical scenarios. We review the important NSCLC clinical trials of the efficacy of EGFR TKIs in the context of EGFR-activating mutations. In all phase II single-arm studies or phase III randomized comparative studies, EGFR TKIs as monotherapy were superior to combination chemotherapy in terms of response rate and progression-free survival in patients with activating EGFR mutations. EGFR TKIs have contributed to the superior overall survival time in NSCLC patients with EGFR mutations compared with those patients without EGFR mutations. The results of these studies have led to a paradigm shift in the treatment of patients with advanced NSCLC. NSCLC with EGFR mutations constitutes a new entity requiring different personalized treatment strategies.     

消癌平注射液联合GP方案治疗晚期非小细胞肺癌的临床研究

目的观察消癌平注射液联合GP方案治疗晚期非小细胞肺癌的临床疗效。方法将56例晚期非小细胞肺癌随机分为两组,对照组28例应用GP方案化疗,试验组28例应用GP方案化疗联合消癌平注射液,2个周期后评价疗效。结果两组患者近期疗效比较差异无统计学意义(P>0.05),但试验组患者治疗后生活质量明显优于对照组(P<0.05),毒副反应轻于对照组(P<0.05)。结论消癌平注射液能减轻GP方案对机体的毒副反应,增强患者对化疗的耐受性。