贝伐珠单抗联合化疗治疗非鳞状细胞非小细胞肺癌的疗效观察

目的：观察贝伐珠单抗联合化疗治疗非鳞状细胞非小细胞肺癌的疗效和安全性.方法：回顾性分析2010年7月-2011年12月解放军总医院经组织病理学证实的局部进展或复发转移的非鳞状细胞非小细胞肺癌患者接受贝伐珠单抗联合化疗方案治疗的临床资料.贝伐珠单抗7.5mg/kg,每3周1次,联合多西他赛、培美曲塞或吉西他滨±铂类化疗.化疗2周期后按实体肿瘤疗效评价标准（RECIST）评价疗效,按美国癌症研究所制定的常见毒性判定标准（NCI-CTC） 3.0版评价不良反应.结果：21例患者中无完全缓解病例,部分缓解4例,稳定13例,进展4例,客观缓解率19.0％（4/21）,疾病控制率81.0％（17/21）,中位无疾病进展时间为7.0月,中位生存时间为10.4月.与贝伐珠单抗相关的不良反应出血6例（28.6％）,高血压1例（4.8％）,主要为Ⅰ、Ⅱ度,Ⅲ、Ⅳ度少见.结论：贝伐珠单抗联合化疗治疗进展或复发的非鳞状细胞非小细胞肺癌疗效确切,耐受性好.     

An exceptional overall survival using bevacizumab beyond progression in a patient with non-small cell lung cancer

Non-small cell lung cancer (NSCLC) is the most common malignancy and the leading cause of cancer death worldwide. In this report, we describe a patient with NSCLC who was treated with continuation of Bevacizumab (Bev) beyond progression to first-line Bev-based chemotherapy. The prolonged treatment with Bev by continuing the inhibition of VEGF beyond first-progression has a strong rationale. Nevertheless, few data exist regarding the efficacy and safety of Bev beyond first line of chemotherapy progression in NSCLC patients. Further studies including a large number of patients are needed, in order to select patients who could benefit from this approach.     

中性粒细胞淋巴细胞比值(NLR)与晚期非小细胞肺癌一线化疗疗效及预后的关系

目的:观察中性粒细胞淋巴细胞比值(NLR)及其动态变化与晚期非小细胞肺癌(NSCLC)患者一线化疗疗效和预后的关系.方法:回顾性分析2011年12月至2016年12月苏州大学附属常州肿瘤医院收治的102例接受一线化疗的晚期NSCLC患者的临床资料.分析患者一线化疗前和2周期后的外周血NLR与临床的相关性,通过建立患者工...     

外周血中性粒细胞与淋巴细胞比值预测晚期非小细胞肺癌免疫治疗疗效的价值

目的:探讨外周血中性粒细胞与淋巴细胞比值（neutrophil-to-lymphocyte ratio,NLR）预测晚期非小细胞肺癌（non-small cell lung cancer,NSCLC）免疫治疗近期疗效的可行性。方法:回顾分析2018年08月至2019年12月收治的60例一线及以上治疗进展后应用帕博丽珠单抗治疗的NSCLC患者的近期疗效及NLR水平变化。根据ROC曲线,将患者治疗前NLR值分为NLR＜2.605组和NLR≥2.605组,分析两组患者治疗前NLR水平,以及治疗前后NLR水平动态变化与患者近期疗效相关性。采用RECIST1.1评价疗效。结果:共计60例患者纳入统计,NLR＜2.605组患者41例, NLR≥2.605组患者19例 ,两组间基本资料差异均无统计学意义（P＞0.05）。NLR＜2.605 组的疾病控制率（disease control rate,DCR）为82.9%,明显优于NLR≥ 2.605组的26.3%,差异有统计学意义 （P＜0.05）。两组患者治疗2个周期后NLR升高≥30%患者的DCR明显低于NLR升高不明显或下降患者（P＜0.05）。结论:外周血NLR水平以及治疗过程中NLR动态变化,可预测非小细胞肺癌免疫治疗的近期疗效。     

贝伐单抗联合化疗治疗晚期多程治疗失败后的非小细胞肺癌临床观察

背景与目的:晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)患者多程治疗失败后,目前尚无标准的化疗方案。本研究旨在观察贝伐单抗联合化疗治疗晚期NSCLC多程治疗失败后的疗效和安全性。方法:2010年1月—2011年2月经病理证实符合入选标准的35例晚期NSCLC患者,接受贝伐单抗联合化疗方案治疗。化疗2个周期后按照实体瘤疗效评价标准(RECIST 1.0)评价疗效。按照美国国立癌症研究所制定的通用药物毒性标准3.0版评价不良反应。结果:35例患者中,30例完成2个周期以上的化疗,32例病例可评价疗效,总体PR 7例,SD 18例,PD 7例,RR为21.9%(7/32),DCR为78.1%(25/32);中位PFS为3个月,中位OS为8个月。与贝伐单抗相关的不良反应以高血压、蛋白尿和出血多见,其中多为Ⅰ、Ⅱ级,Ⅲ、Ⅳ级少见。结论:贝伐单抗联合化疗对晚期多程治疗失败后的NSCLC有一定的抗肿瘤活性和较高的疾病控制率,安全性较高,临床受益率高,是一种有临床应用前景的治疗方法。     

贝伐单抗联合培美曲塞加顺铂治疗晚期非小细胞肺癌疗效与安全性的Meta分析

目的:系统评价贝伐单抗联合培美曲塞加顺铂治疗晚期非小细胞肺癌(NSCLC)的疗效与安全性.方法:计算机检索PubMed、Medline、CNKI、VIP和万方医学网等数据库,纳入贝伐单抗联合培美曲塞加顺铂比较治疗晚期非小细胞肺癌的临床随机对照试验,检索时间截至2016年11月.对所检索文献进行文献筛选、资料提取和方法学质量评价后,采用RevMan5.3.0软件进行Meta分析.结果:共纳入10个研究,合计1 094例患者.研究结果显示:在疗效评价方面,含贝伐单抗治疗的观察组在客观有效率(OR=2.63,95%CI:2.04~3.38,P<0.000 01)、中位无进展生存期(mPFS)(X2=15.976,P=0.016 17)方面与不含贝伐单抗的对照组的差异有统计学意义,观察组的疗效明显高于对照组;而在疾病控制率、mOS及安全性方面,贝伐单抗组疾病控制率(OR=2.52,95%CI:1.88~3.38,P<0.000 01)、中位生存期(mOS)(X2 =5.316 2,P=0.050 02)、恶心、呕吐(OR=0.87,95%CI:0.64~1.19,P=0.38),血小板减低(OR=1.01,95%CI:0.61~1.68,P=0.96),中性粒细胞减低(OR=1.38,95%CI:0.90~2.12,P=0.14)及贫血(OR=0.99,95%CI:0.46~2.12,P=0.97)的发生率与不含贝伐单抗组相同.但是高血压(OR=3.92,95%CI:1.05~14.62,P=0.04)、出血(OR=5.29,95%CI:0.87~32.31,P=0.07)的发生率却明显高于不含贝伐单抗组.结论:贝伐单抗联合培美曲塞加顺铂比培美曲塞加顺铂治疗非小细胞肺癌的疗效较高,不良反应较少.     

Antiangiogenic agents and chemotherapy in advanced non-small cell lung cancer: a clinical perspective

Antiangiogenic agents represent a major advance in the management of patients with advanced non-small-cell lung cancer receiving chemotherapy. While bevacizumab has been available for first-line treatment, other drugs, such as nintedanib, recently demontrated significant activity in the second-line setting. This review covers most recent results with antiangiogenic treatments, focusing on data relevant for routine clinical practice; recent results potentially leading to new agents approval are discussed. While biomarkers are still awaited to better-select patients for these approaches, the development of antiangiogenic agents represent a model for implementation in thoracic oncology, while highlighting the promise of a better outcome for patients with advanced lung cancer.     

Spinal cord infarction in a patient with metastatic non-small cell lung cancer, receiving chemotherapy combined with bevacizumab

Bevacizumab is an anti-angiogenesis agent that has many applications in the current management of patients with cancer, including advanced non-small cell lung cancer. Its value is however, not without side effects. We present the first reported case of spinal cord infarction in the setting of bevacizumab use in a 70-year old woman with advanced non-small cell lung cancer.     

Clinical trials of antiangiogenic therapy in non-small cell lung cancer: focus on bevacizumab and ZD6474

Lung cancer is the leading cause of cancer deaths in the USA. Despite the development of new chemotherapy regimens, the prognosis remains poor. Several studies comparing various platinum-based regimens failed to produce a significant impact in the outcomes for patients with non-small cell lung cancer and this therapeutic modality appears to be reaching a plateau. It has become clear that further advances will require the addition of agents with a different mechanism of action. Bevacizumab is the antiangiogenic agent at the most advanced stage of development in the treatment of cancer. Bevacizumab is synergistic with chemotherapy and usually well tolerated. The addition of bevacizumab to chemotherapy improved survival in patients with metastatic non-small cell lung cancer in a randomized clinical trial. Several small molecule antiangiogenic agents are in development. In this article, currently available data from clinical trials of antiangiogenic compounds in advanced non-small cell lung cancer are reviewed.     

老年晚期非小细胞肺癌患者ＥＧＦＲ基因的突变研究

目的　探讨老年晚期非小细胞肺癌（ＮＳＣＬＣ）患者ＥＧＦＲ基因突变情况及其与临床病理特征之间的关系。方法　采用ＰＣＲ扩增和实时荧光ＰＣＲ技术分析ＮＳＣＬＣ中ＥＧＦＲ基因第１９和２１号外显子的突变情况。结果　８６例老年ＮＳＣＬＣ酪氨酸激酶域存在体细胞突变２５例（２９.１％）,其中第１９号外显子的缺失突变为１３例（１５.１％）,第２１号外显子的替代突变为１２例（１４.０％）。肺腺癌、肺泡癌的突变率为３６.４％（２４／６６）,高于鳞癌的６.３％（１／１６）;女性患者突变率为４８.３％（１４／２９）,高于男性患者的１９.３％（１１／５７）;非吸烟患者的突变率为４３.９％（１８／４１）,高于长期吸烟者的１５.６％（７／４５）。结论 中国老年ＮＳＣＬＣ患者ＥＧＦＲ基因酪氨酸激酶区第１９和２１外显子的突变特征与肺癌总体患者类似,与年龄关系不大,突变率以腺癌、女性及非吸烟者较高。老年ＮＳＣＬＣ患者同样可以通过基因检测获得ＴＫＩ治疗预测信息。     

Survival outcome according to KRAS mutation status in newly diagnosed patients with stage IV non-small cell lung cancer treated with platinum doublet chemotherapy

Introduction

Mutations (MT) of the KRAS gene are the most common mutation in non-small cell lung cancer (NSCLC), seen in about 20–25% of all adenocarcinomas. Effect of KRAS MT on response to cytotoxic chemotherapy is unclear.

Methods

We undertook a single-institution retrospective analysis of 93 consecutive patients with stage IV NSCLC adenocarcinoma with known KRAS and EGFR MT status to determine the association of KRAS MT with survival. All patients were treated between January 1, 2008 and December 31, 2011 with standard platinum based chemotherapy at the University of Pennsylvania. Overall and progression free survival were analyzed using Kaplan-Meier and Cox proportional hazard methods.

Results

All patients in this series received platinum doublet chemotherapy, and 42 (45%) received bevacizumab. Overall survival and progression free survival for patients with KRAS MT was no worse than for patients with wild type KRAS. Median overall survival for patients with KRAS MT was 19 months (mo) vs. 15.6 mo for KRAS WT, p = 0.34, and progression-free survival was 6.2 mo in patients with KRAS MT vs. 7mo in patients with KRAS WT, p = 0.51. In multivariable analysis including age, race, gender, and ECOG PS, KRAS MT was not associated with overall survival (HR 1.12, 95% CI 0.58–2.16, p = 0.74) or progression free survival (HR 0.80, 95% CI 0.48–1.34, p = 41). Of note, receipt of bevacizumab was associated with improved overall survival only in KRAS WT patients (HR 0.34, p = 0.01).

Conclusions

KRAS MT are not associated with inferior progression-free and overall survival in advanced NSCLC patients treated with standard first-line platinum-based chemotherapy.     

贝伐珠单抗联合厄洛替尼治疗NSCLC疗效及安全性Meta分析

目的 贝伐珠单抗(bevacizumab,B)及厄洛替尼(erlotinib,E)作用于不同的靶点,在抗肿瘤机制中有相互补充的作用,本研究通过Meta分析比较贝伐珠单抗联合厄洛替尼(B+E)与贝伐珠单抗单药治疗(Bevacizumab,B)或联合化疗(B+chem)对非小细胞肺癌(non-small cell lung cancer,NSCLC)患者的疗效及安全性.方法 计算机检索Medline、web of science、Cochrane library和EMbase等数据库,结合手工检索,检索时间至2016-12-18,收集比较B+E与B或B+chem治疗NSCLC的临床试验,按照Cochrane系统评价方法,采用 RevMan 5.3软件进行 Meta 分析,分析了无进展生存期(progression-free-survival,PFS)、总生存期(overall survival,OS)和不良事件(adverse event)等结局指标.结果 共纳入6项临床试验.B+E与B单药治疗相比,能够提高患者的PFS,HR=0.65,95%CI为0.57~0.74;两组OS差异无统计学意义,HR=0.96,95%CI为0.83~1.11.对于EGFR突变的患者,B+E与B单药治疗相比,能够提高患者的PFS,HR=0.43,95%CI为0.30~0.61;而在EGFR野生型患者中,B+E与B单药治疗PFS差异无统计学意义,HR=0.85,95%CI为0.70~1.04.而B+E与B+chem治疗相比,B+E组PFS(HR=1.88,95%CI为1.45~2.44)及OS(HR=1.36,95%CI为1.03~1.79)均显著低于B+chem组.EGFR突变的患者,B+E与B+chem相比,PFS差异无统计学意义,HR=0.58,95%CI为0.22~1.55).而在EGFR野生型患者中,B+E与B+chem相比,PFS更短,HR=1.96,95%CI为1.37~2.82.B+E方案可能会增加患者发生3~4级皮疹及腹泻的可能.结论 在NSCLC患者中,B+E治疗方案与B单药治疗相比具有更好的疗效,然而与B+chem方案相比,B+E方案仅在EGFR突变患者中具有更好的疗效.结果仍需大样本量研究证实.     

甲磺酸阿帕替尼治疗晚期非小细胞肺癌的研究现状

甲磺酸阿帕替尼,一种小分子酪氨酸激酶抑制剂(tyrosine kinase inhibitor,TKI),作用于血管内皮生长因子受体-2(vascular endothelial growth factor receptor-2,VEGFR-2),强效抑制内皮细胞新生血管生成。阿帕替尼是在中国获得批准的第一代口服抗血管生成药物,用于晚期胃癌标准化疗失败的后续治疗。目前阿帕替尼单药或者联合其他治疗在晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)中的临床研究正在积极开展,多数均显示一定生存获益。本文详细介绍近年阿帕替尼在晚期NSCLC中的研究现状,为后期临床应用提供参考。     

贝伐珠单抗联合化疗治疗复治晚期非鳞非小细胞肺癌的疗效及安全性观察

目的 探讨贝伐珠单抗联合化疗治疗复治晚期非鳞非小细胞肺癌（NSCLC）的疗效及安全性。方法 收集本院2010年5月至2014年7月经病理证实符合入选标准的84例复治晚期NSCLC患者,接受贝伐珠单抗联合化疗方案治疗,化疗2个周期后按照实体瘤疗效评价标准（RECIST 1.0）评价疗效,按照美国国立癌症研究所制定的通用药物毒性标准3.0版评价不良反应,采用Kaplan-Meier法进行生存分析。结果 84例患者均可评价疗效且无CR病例,其中获PR 12例,SD 42例,PD 30例,有效率和疾病控制率分别为14.8%和64.8%;全组的中位无进展生存期和总生存期分别为3.8个月和8.8个月;不良反应主要为骨髓抑制、高血压、肝功能损害、皮疹等,以1、2级为主。结论 贝伐珠单抗联合化疗治疗晚期非鳞NSCLC的疗效好,不良反应轻,值得临床上推广。     

贝伐单抗治疗晚期非小细胞肺癌的疗效与安全性临床研究进展

抗血管生成治疗是肿瘤常见的治疗方式之一。贝伐单抗作为抗血管内皮生长因子的单克隆抗体,是目前唯一被批准用于晚期非小细胞肺癌（non-small cell lung cancer,NSCLC）一线治疗的抗血管生成制剂。为了扩大贝伐单抗用于晚期NSCLC的适应证,大量研究继续探索贝伐单抗在一线治疗的联合形式外,还致力于探索其在后线及跨线治疗的疗效和安全性。本文就近年来贝伐单抗用于晚期NSCLC治疗的疗效与安全性临床研究进展进行综述。      

吉非替尼治疗23例晚期非小细胞肺癌

背景与目的:有临床研究表明分子靶向药物吉非替尼单药治疗NSCLC有效,本文旨在研究吉非替尼治疗晚期非小细胞肺癌的疗效及其安全性。方法:23例晚期非小细胞肺患者每日均口服吉非替尼250mg,直至患者不能耐受或病情进展时停药,观察患者症状、近期疗效、肿瘤无进展时间、生存期及不良反应。结果:23例患者至少服药1个月,其中用药后咳嗽、胸痛等症状缓解的有13例,无缓解的有3例,病情持续加重的有7例。影像学显示,肺、脑等转移灶减小的有11例(47.8%),无变化或增大的各6例(各占26.1%)。CR2例(8.7%),PR10例(43.5%),SD4例(17.4%),PD7例(30.4%)。有效率(RR)为52.2%,疾病控制率(DCR)为69.6%。患者肿瘤无进展中位时间5个月(0～15个月),至随访结束时,8例死亡,15例生存。副作用有皮疹10例(43.5%),4例(17.4%)消化道反应表现为溃疡与腹泻症状。结论:用吉非替尼治疗晚期非小细胞肺癌效果较好且安全。     

Gemictabine plus carboplatin in patients with advanced non-small cell lung cancer

To evaluate the efficacy and safety of gemictabine combined with carboplatin for a chemotherapy regimen for patients with metastatic, recurrent, or locally advanced non-small cell lung cancer (NSCLC), 46 chemotherapy-naïve patients with histologically confirmed stage IIIB or IV NSCLC were treated with 1250 mg/m² of gemictabine on d 1 and 8, with carboplatin of AUC 6 additionally applied on d 1. This treatment was repeated every 3 wk. In all, a total of 215 chemotherapy courses were administered. The median age of the patients was 46, ranging from 33 to 83. Ten patients (22%) had an ECOG performance status of 2. Responses were observed objectively in 20 patients (43.5%) and maintained for a median of 7.4 mo. The median duration of progression-free and overall survivals were 5.0 and 12.3 mo, respectively. Neutropenia was frequently encountered, and gastrointestinal side effects, such as anorexia and nausea, were mostly predictable but manageable. One patient died of septic shock due to a complication with pneumonia while simultaneously trying to recover from myelosuppression. A subgroup consisting of patients aged 65 yr or older and/or PS 2 showed a outcome similar with the entire group of all patients involved in the study: response rate (43.5%), median PFS (4.6 months), median OS (12.3 months), and similar toxicity rate. After analyzing all the results, it was evident that a treatment of gemcitabine combined with carboplatin is an active and safe regimen for first-line treatment of advanced NSCLC. The results of the elderly and/or PS 2 patients were similar to those of the entire group of patients.     

炎性复合指标与非小细胞肺癌预后关系的研究进展

肺癌是一种炎症相关性疾病,长期慢性肺部炎症可增加肺癌罹患风险。非小细胞肺癌（non-small cell lung cancer,NSCLC）为肺癌最常见类型,具有发病率高,早期确诊率低,预后差的特点。研究表明,肿瘤相关性炎症反应广泛参与肿瘤起始、增殖、侵袭及转移各阶段,与疾病预后密切相关。基于炎症标志物建立的炎性复合指标有望成为非小细胞肺癌预后评估的有效指标,对准确评估病情、识别生存风险、改善远期预后具有现实意义。     

NOB1 expression predicts early response to cisplatin-based chemotherapy in patients with advanced non-small cell lung cancer

Background: The aim of this study was to investigate the predictive value of Nin one binding (NOB1) expression for response to cisplatin-based chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC).

Methods: A total of 105 consecutive patients with advanced NSCLC were retrospectively investigated between January 2012 and June 2014. We used transbronchial biopsy to collect cancer tissue samples. Immunohistochemistry were used in the detection of NOB1 protein expression. We assessed the chemotherapy early response by response evaluation criteria in solid tumours (RECIST) Version 1.1 at the end of the second cycle of chemotherapy.

Results: In the 105 transbronchial biopsy NSCLC specimens, 22 (21.0%) stained NOB1 ??, 35 (33.3%) stained +, 31 (29.5%) stained ++ and 17 (16.2%) stained +++. The early response rate to chemotherapy was 59.0% in overall NSCLC. Early response to chemotherapy has no relationship with patients' age, gender, smoke status, performance status and chemotherapy regimens (P>0.05), but related with TMN stage, histopathological grade, as well as NOB1 expression (P?P?=?0.008) for early response to chemotherapy.

Conclusion: Our results suggest that enhanced expression of NOB1 related with poor early response to cisplatin-based chemotherapy in patients with advanced non-small cell lung cancer.     

Phase 2 trial of maintenance bevacizumab alone after bevacizumab plus pemetrexed and carboplatin in advanced,nonsquamous nonsmall cell lung cancer

BACKGROUND:

The authors performed a phase 2 study of bevacizumab plus pemetrexed and carboplatin followed by maintenance bevacizumab in patients with advanced, nonsquamous nonsmall cell lung cancer.

METHODS:

Previously untreated patients with advanced, nonsquamous nonsmall cell lung cancer and an Eastern Cooperative Oncology Group performance status of 0 or 1 received bevacizumab 15 mg/kg, pemetrexed 500 mg/m² and carboplatin at an area under the concentration‐time curve of 6 intravenously on day 1 every 21 days. Responding or stable patients who completed 6 cycles then received bevacizumab maintenance every 21 days until disease progression.

RESULTS:

In total, 43 patients (40 who were evaluable for response) were entered on the study. Treatment‐related grade 3/4 toxicities were low and included febrile neutropenia (2%), neutropenia (28%), anemia (18%), thrombocytopenia (11%), hypertension (7%), epistaxis (5%), venous thrombosis (8%), dyspnea (7%), rectovaginal fistula (2.3%), infusion reaction (2%), and cerebrovascular event (2%). One patient died from complications of venous thromboembolism and cerebrovascular accident after Cycle 2. Minimal clinically significant toxicity occurred during maintenance bevacizumab. Two complete responses (5%) were observed, and 17 patients (42%) had a partial response. Fifteen patients (38%) displayed disease stability. The overall disease control rate was 85%. At a median follow‐up of 15.8 months, the median progression‐free survival was 7.1 months (95% confidence interval, 5.9‐8.3 months), and the median overall survival was 17.1 months (95% confidence interval, 8.8‐25.5 months).

CONCLUSIONS:

Combined bevacizumab, pemetrexed, and carboplatin followed by maintenance bevacizumab was well tolerated and displayed remarkable activity in patients with previously untreated, advanced, nonsquamous nonsmall cell lung cancer. Cancer 2012. © 2012 American Cancer Society.