贝伐珠单抗在非小细胞肺癌中应用的研究现状

目前非小细胞肺癌化疗疗效已经达平台期,亟需寻找新的方法提高疗效。贝伐珠单抗是一种重组抗VEGF单克隆抗体,是首个证实与化疗联合可提高晚期NSCLC 患者生存的靶向治疗药物。近年来许多关于贝伐珠单抗在NSCLC 一线、二线、辅助、新辅助治疗、联合放化疗,安全性及预测标志物的临床研究,现将其研究现状做一综述。      

非小细胞肺癌骨转移特征与预后的相关性

摘 要：［目的］ 分析非小细胞肺癌(non-small cell lung cancer,NSCLC)骨转移的临床特征及影响预后生存的相关因素。［方法］ 回顾性分析辽宁省肿瘤医院2011年6月至2014年6月确诊非小细胞肺癌患者117例,统计其6个月、1年、2年生存率,并计算中位生存期（median overall survival,mOS）,分析影响骨转移患者生存的预后因素。［结果］在PS评分低或高(15.1m vs 11.6m)、骨转移灶单病灶或多病灶(15.7m vs 11.9m)、中轴骨或四肢骨转移(14.9m vs 11.2m)、双膦酸盐治疗(15.3m vs 11.3m)四组的中位生存期均有统计学差异(P值均<0.05)。 Cox回归模型中PS评分、骨转移位置、双膦酸盐组间具统计学意义。［结论］ PS评分、骨灶位置、双膦酸盐治疗是非小细胞肺癌骨转移预后的独立的因素。     

伴远处孤立转移的非小细胞肺癌治疗进展

肺癌是严重威胁人类健康及生命的恶性肿瘤之一,发病率逐年上升.非小细胞肺癌(NSCLC)中Ⅳ期患者可达40%左右.而其中一小部分Ⅳ期NSCLC患者呈单脏器孤立转移,且原发灶亦为早期.对此部分患者,其治疗方式同初治时即有多部位远处转移者有所不同;同样,其预后同初治时即有多部位远处转移者亦不相同.对于孤立脑转移患者.在原发NSCLC能够完全切除或已经得到良好控制的情况下,切除同时性或异时性孤立脑转移的5年生存率高达10%～30%,目前的标准治疗推荐手术切除原发灶及孤立脑转移灶或立体定向放疗联合全脑放疗.而孤立肾上腺转移发生率大约在1.62%～3.5%.通过积极的外科切除及联合化疗,NSCLC同时或异时性孤立肾上腺转移患者能延长生存并可获长期生存,5年生存率可达25%～40%.查阅大量相关文献,得出结论认为:对于伴有不同部位的远处孤立转移非小细胞肺癌患者,在原发灶完全切除基础上,进行积极的转移灶局部手术治疗,生存期明显优于其它Ⅳ期患者.     

非小细胞肺癌的巩固性治疗

恶性肿瘤巩固性治疗的概念,从广义上说是指肿瘤经过手术、放疗、化疗等主体治疗取得疗效后,为了达到根治或延长生存期所采取的治疗措施,巩固其治疗效果.包括术后辅助治疗、化疗取得疗效后的维持治疗,以及完成主体治疗后的巩固性治疗.要想把非小细胞肺癌变成一种可治性疾病,巩固性治疗是综合治疗中的一个至关重要的环节.非小细胞肺癌的巩固性治疗包括:巩固性化学治疗、巩固性生物治疗和巩固性中药治疗.     

非小细胞肺癌的淋巴结转移相关因素及规律的探讨

  目的  探讨原发性非小细胞肺癌(NSCLC)年龄、性别、吸烟指数、肿瘤大小、病理类型、细胞分化程度与淋巴结转移的关系, 分析纵隔淋巴结转移的临床规律及分布特点。  方法  对96例非小细胞肺癌行肺切除术和淋巴结清扫术的患者进行临床病理分析。  结果  淋巴结转移与年龄、性别、吸烟指数无关, 肿瘤大小与淋巴结转移差异无统计学意义。高、中、低分化癌淋巴结转移率分别为15.8%、47.8%和59.0%, 肿瘤分化程度越低, 纵隔淋巴结转移率越高(P < 0.05)。病理类型与淋巴结转移无相关性, 鳞癌、腺癌的N₂转移率分别为13.6%、34.0%。肺腺癌较鳞癌易发生纵隔淋巴结转移(P < 0.05)。中心型肺癌与周围型肺癌纵隔淋巴结转移率差异无统计学意义(P > 0.05)。跳跃性N₂有12例, 跳跃式纵隔转移共9例。肺癌常跨区域纵隔转移, 肺下叶癌跨区域纵隔转移与肺上叶癌比较差异无统计学意义(P > 0.05)。  结论  非小细胞肺癌的淋巴结转移与细胞分化程度有密切关系, 与年龄、性别、吸烟指数、病理类型、原发肿瘤大小无关; 肺腺癌较鳞癌易发生纵隔淋巴结转移; 多数肺癌的淋巴结转移遵循由近及远、自上而下、由肺内经肺门再向纵隔的顺序转移规律; 部分纵隔淋巴结的转移呈"跳跃式"; 肺切除术时,施行系统性胸内淋巴结清扫是必要的。      

非小细胞肺癌脑转移的药物治疗进展

肺癌发病率和病死率高,最常见的病理类型为非小细胞肺癌,24%～40%的晚期非小细胞肺癌患者出现脑转移,预后不良。手术治疗以及传统放疗效果并不理想,血脑屏障也阻碍了化疗药物发挥其疗效。近年来,靶向药物及免疫治疗的出现为非小细胞肺癌脑转移患者提供了新的治疗希望,该文就目前非小细胞肺癌脑转移患者的药物治疗方式展开了全面综述,比较各类药物单用及联用的临床疗效,为非小细胞肺癌脑转移患者提供更合理的治疗方案建议。     

多西紫杉醇和顺铂联合全脑放疗治疗非小细胞肺癌脑转移的疗效

目的探讨多西紫杉醇和顺铂联合全脑放疗,治疗非小细胞肺癌脑转移的近期疗效及患者生存期和生存质量。方法将40例非小细胞肺癌脑转移患者随机分为A组和B组,各20例。A组,采用＂多西紫杉醇＋卡铂＂方案：多西紫杉醇75 mg/m2,d1;顺铂40 mg/m2,d1～2。B组,采用＂替尼泊甙＋顺铂＂方案：替尼泊甙60 mg/m2,d1～5;顺铂40 mg/m2,d1～2。每21天为1个周期。脑部放疗：6MV-X线直线加速器,脑部病灶≤3个,全脑放疗40 Gy/20次后,根据情况缩野加量14～16 Gy/7～8次;脑部病灶〉3个,全脑放疗至40 Gy/20次。全脑放疗至20～30 Gy/10～15次时同时行化疗。结果对脑转移的控制有效率（CR＋PR）A组为70.0%（14/20）,B组为65.0%（13/20）,两组比较无显著性差异（P〉0.05）;中位生存期两组分别为14和9个月;中位肿瘤进展时间（mTTP）分别为9.7和6.3个月,两组比较有显著性差异（P〈0.05）;1年生存率两组分别为65.0%（13/20）和30.0%（6/20）,两者比较有显著性差异（P〈0.05）。两组治疗前后KPS评分比较,差异有统计学意义。结论多西紫杉醇和顺铂联合全脑放疗对非小细胞肺癌脑转移控制率无明显提高,但延长了患者生存期及肿瘤进展时间（TTP）,具有较好疗效。     

Bevacizumab Concomitant with Chemotherapy is Effective in Treating Chinese Patients with Advanced Non-Squamous Non-Small Cell Lung Cancer

Objectives: To retrospectively review the safety and clinical efficacy of bevacizumab concomitant withchemotherapy in Chinese patients with advanced non-squamous non-small cell lung cancer (NSNSCLC). Methods:Clinical data for 79 patients with NSNSCLC who received bevacizumab concomitant with chemotherapy inChinese PLA General Hospital from April 28th 2009 to May 5th 2013 were retrospectively reviewed to analyzethe clinical efficacy including disease control rate (DCR), overall response rate (ORR), progression-free survival(PFS), overall survival (OS), the Eastern Cooperative Oncology Group (ECOG) score and the safety. Results:The Eastern Cooperative Oncology Group (ECOG) score was 0-2. By the final cutoff date (June 9, 2013), 54(68.4%) patients had disease progression and 37 (46.8%) died. The ORR was 32.9% and the DCR was 83.5%.The ORR of the first-, second-, and third- or later-line treatments were 51.4%, 25.0% and 12.5%, while the DCRwere 94.3%, 80.0% and 70.8%, respectively. The median OS (mOS) and PFS (mPFS) were 13.5 and 5.83 months,respectively. The mOS of patients with the first-, second-, and third- or later- line treatments were 16.2, 10.9and8.30 months, while the mPFS were 7.27, 5.90 and 5.17 months, respectively. Chemotherapy-related adverseevents included myelosuppression, vomiting, hepatic dysfunction and renal dysfunction, while the commonserious bevacizumab-related adverse events were thromboembolic problems, gastrointestinal perforation andreversible posterior leukoencephalopathy syndrome, which could be well managed. Conclusions: Bevacizumabconcomitant with chemotherapy is effective and the related toxicity can be well tolerated in Chinese patientswith NSNSCLC.     

羟基喜树碱治疗非小细胞肺癌的临床研究

目的:观察拓扑异构酶Ⅰ、Ⅱ抑制剂按时间顺序给药的临床疗效及不良反应。方法:观察组化疗方案为HP-EP-HP-EP,对照组为CAP-EP-CAP-EP。HCPT10～12mg/m2静推d1～5,DDP80mg/m2ivgtt分3天使用,VP-16100mg/m2ivgttd1,3,5,ADM40mg/m2静推d1,CTX400mg/m2静推d1,d8。上述方案每3周为1周期,交替使用,4个周期为一观察疗程。结果:观察组60例患者完成一个疗程具有可评价者54例,有效率51.85%;对照组60例患者完成一个疗程具有可评价者58例,有效率32.76%,两组间有显著性差异(P<0.05)。不良反应:两组均出现血象下降、消化道反应、脱发等,两组间无显著性差异(P>0.05)。结论:观察组疗效确切,不良反应可以耐受,说明拓扑异构酶Ⅰ、Ⅱ抑制剂按时间顺序给药有较好疗效,具有一定的临床应用价值。     

Systematic Analysis of Icotinib Treatment for Patients with Non-Small Cell Lung Cancer

Purpose: This analysis was conducted to evaluate the efficacy and safety of icotinib based regimens in treatingpatients with non-small cell lung cancer (NSCLC). Methods: Clinical studies evaluating the efficacy and safetyof icotinib-based regimens with regard to response and safety for patients with NSCLC were identified usinga predefined search strategy. Pooled response rates of treatment were calculated. Results: With icotinib-basedregimens, 7 clinical studies which including 5,985 Chinese patients with NSCLC were considered eligible forinclusion. The pooled analysis suggested that, in all patients, the positive reponse rate was 30.1% (1,803/5,985)with icotinib-based regimens. Mild skin itching, rashes and diarrhea were the main side effects. No grade III orIV renal or liver toxicity was observed. No treatment-related death occurred in patients treated with icotinibbasedregimens. Conclusions: This evidence based analysis suggests that icotinib based regimens are associatedwith mild response rate and acceptable toxicity for treating Chinese patients with NSCLC.     

蛋白激酶C抑制剂与非小细胞肺癌的治疗

蛋白激酶C(protein kinase C,PKC)是细胞内信号转导中的关键部分,参与细胞信息传递、分泌、离子通道调节、细胞增殖、分化、凋亡及癌变等一系列过程;PKC是肿瘤细胞活化的重要信号分子,参与肿瘤发生、发展的调控.     

Management of Non-Small Cell Lung Cancer with Oligometastasis

Patients with oligometastatic Non-Small Cell Lung Cancer (NSCLC) present a potential opportunity for curative therapy; however, the challenge remains the definitive treatment of their localized disease and ablation of their limited overt metastatic sites of disease. In selecting patients with oligometastatic NSCLC for definitive therapy, proper staging through radiographic studies, including PET and brain MRI, and the pathologic staging of the mediastinal lymph nodes and potential sites of metastatic disease, are critical. With that in mind, the available literature suggests that in highly selected patients with solitary metastases to the brain, adrenals and other organs, long term survival may be achieved with combined definitive therapy of both the primary lung tumor and the solitary metastatic site.     

力尔凡对晚期非小细胞肺癌化疗的影响

比较全身化疗加或不加力尔凡对晚期非小细胞肺癌(NSCLC)的疗效、不良反应及免疫功能的变化。方法:将60例晚期NSCLC患者以随机方法(开信封)分别分为并用力尔凡组(治疗组)和单用化疗组(对照组),分别接受NP方案(诺维苯、顺铂)加力尔凡或单用NP方案化疗。结果:1)治疗组部分缓解率43.3%,对照组33.3%(P>0.05),中位缓解期分别为4.8个月及3.3个月。2)治疗组疗后和疗前相比CD4及CD4/CD8值显著升高(P<0.05),而对照组则相反,两组差异显著(P<0.05)。3)不良反应:治疗组白细胞下降63.3%,对照组达100%(P<0.05)。结论:力尔凡与化疗同时应用治疗晚期NSCLC,疗效有所提高,可增强细胞的免疫功能,对化疗引起的白细胞下降有保护作用。     

局部热疗联合全身化疗治疗晚期非小细胞肺癌的系统评价

背景与目的肿瘤热疗与化疗具有协同作用,应用越来越广泛。本文系统评价局部热疗联合全身化疗治疗晚期非小细胞肺癌的疗效和副作用。     

Cell Free EGFR mRNA Expression and Implications for Survival and Metastasis in Non-Small Cell Lung Cancer Cases

Background: NSCLC is a disease involving uncontrolled cell growth, which could result in metastases intonearby tissues beyond the lungs. Materials and Methods: The aim of the present study was to analyze the influenceof epidermal growth factor receptor (EGFR) gene expression on metastasis and survival in NSCLC patients.The present case-control study included 100 cases of NSCLC patients and 100 age and sex matched controls.EGFR gene expression was analyzed by quantitative real time PCR using serum RNA. Association with NSCLCpatient survival was analyzed by the Kaplan-Meier method. Results: We analyzed EGFR gene expression andobserved mean increased gene expression of 13.5 fold in NSCLC patients. Values reflected overall survival ofpatients with a median of 15.8 months in the cases of <13 fold increased gene expression vs 6.7 months with >13fold increased EGFR gene expression (p=0.005). Distant metastatic patients with <13 fold increased EGFR geneexpression had 7.9 months of median survival time while>13 fold increased EGFR gene expression had only 5months of median survival time (p=0.03). Non metastatic patients with <13 fold increased EGFR gene expressionhad 18 months of median survival time as compared to only 7.1 months with >13 fold increased expression.Conclusions: Higher cell free EGFR mRNA expression may play an important role in causing distant metastasesand reducing overall survival of NSCLC patients in the Indian population.