以培美曲塞为基础的联合化疗方案治疗老年人晚期非鳞非小细胞肺癌的临床研究

目的 评估以培美曲塞为基础的联合化疗方案一线治疗老年晚期非鳞非小细胞肺癌（NSCLC）患者的临床效果和安全性。方法 回顾性分析经病理学确诊的老年晚期非鳞NSCLC患者40例,采用培美曲塞联合顺铂或卡铂方案全身化疗,其中培美曲塞联合顺铂组（A组）18例,培美曲塞联合卡铂组（B组）22例,根据实体瘤疗效评价标准（RECIST）和美国国家癌症研究所化疗毒性分级标准（NCI-CTC AE）对疗效和不良反应进行评估。结果 40例老年晚期非鳞NSCLC患者经培美曲塞为基础的化疗方案治疗后,部分缓解 17例,稳定16例,进展7例,客观有效率（ORR）42.5 %（17／40）,疾病控制率（DCR）82.5 %（33／40）,中位无进展生存（PFS）5.3个月,1年生存率63.2 %（24／38）。亚组分析A组与B组相比,ORR分别为44.4 %（8／18）、40.9 %（9／22）,DCR分别为83.3 %（15／18）、81.8 %（18／22）,PFS分别为5.5、5.1个月,1年生存率分别为64.7 %（11／17）、 61.9 %（13／21）,前者均高于后者,但差异均无统计学意义（均P＞0.05）。全组患者不良反应较轻,主要为骨髓抑制和胃肠道反应,多为1、2级。结论 在老年患者中,应用以培美曲塞为基础的方案治疗晚期非鳞NSCLC具有良好效果,且不良反应较小,能耐受,可推荐作为体力状况（PS）评分较好的老年晚期非鳞NSCLC的一线化疗方案。     

Phase I trial of axitinib combined with platinum doublets in patients with advanced non-small cell lung cancer and other solid tumours

Background:

This phase I dose-finding trial evaluated safety, efficacy and pharmacokinetics of axitinib, a potent and selective second-generation inhibitor of vascular endothelial growth factor receptors, combined with platinum doublets in patients with advanced non-small cell lung cancer (NSCLC) and other solid tumours.

Methods:

In all, 49 patients received axitinib 5 mg twice daily (b.i.d.) with paclitaxel/carboplatin or gemcitabine/cisplatin in 3-week cycles. Following determination of the maximum tolerated dose, a squamous cell NSCLC expansion cohort was enroled and received axitinib 5 mg b.i.d. with paclitaxel/carboplatin.

Results:

Two patients experienced dose-limiting toxicities: febrile neutropenia (n=1) in the paclitaxel/carboplatin cohort and fatigue (n=1) in the gemcitabine/cisplatin cohort. Common nonhaematologic treatment-related adverse events were hypertension (36.7%), diarrhoea (34.7%) and fatigue (28.6%). No grade⩾3 haemoptysis occurred among 12 patients with squamous cell NSCLC. The objective response rate was 37.0% for patients receiving axitinib/paclitaxel/carboplatin (n=27) and 23.8% for patients receiving axitinib/gemcitabine/cisplatin (n=21). Pharmacokinetics of axitinib and chemotherapeutic agents were similar when administered alone or in combination.

Conclusion:

Axitinib 5 mg b.i.d. may be combined with standard paclitaxel/carboplatin or gemcitabine/cisplatin regimens without evidence of overt drug–drug interactions. Both combinations demonstrated clinical efficacy and were well tolerated.     

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.     

Treatment patterns and outcomes in patients with non-squamous advanced non-small cell lung cancer receiving second-line treatment in a community-based oncology network

Objectives

This retrospective study used the US Oncology iKnowMed™ database, billing claims, and chart reviews to report treatment patterns and outcomes in late-stage non-small cell lung cancer (NSCLC) in US community oncology practices.

Materials and methods

Eligibility criteria included non-squamous NSCLC, stage IIIB/IV at diagnosis, ECOG performance status (PS) <3, and initiation of 2nd-line therapy (defined as index date) between 1/1/2007 and 6/30/2011 with ≥1 year follow-up. Key outcomes were overall survival (OS), progression-free survival (PFS), time-to-progression (TTP), and time-to-hospitalization (post-index date). Kaplan–Meier and Cox proportional hazard models were used to characterize the distribution and predictors of outcomes.

Results

1168 patients were eligible for the study. The most frequent 2nd-line therapies were pemetrexed (54.4%), erlotinib-containing regimens (17.6%), and docetaxel (10.0%). Median OS and PFS were 7.5 (95% confidence interval [CI]: 6.6–8.4) and 4.1 (95% CI: 3.7–4.5) months, respectively; 57% of patients were hospitalized post-index date. EGFR testing rates were 2.3% before 2010, 15.2% in 2010, and 32.0% in 2011 (P < .001). Of EGFR-positive patients, 50.0% received erlotinib-containing regimens compared with 16.9% of EGFR-negative patients (P = 0.001). An increased risk of shorter time-to-hospitalization, after controlling for other covariates, was associated with PS = 1 (hazard ratio [HR] = 1.51; P < .001) or PS = 2 (HR = 1.68; P = .001) compared with PS = 0, pre-existing comorbid fatigue (HR = 1.64; P = .003) compared with no comorbid fatigue, and progression (HR = 1.92; P < .001), when it occurred, compared with no progression. Compared with other 2nd-line treatment, erlotinib-containing regimens prolonged adjusted TTP (HR = 0.69; P = .015).

Conclusions

This retrospective observational study provides new insights into treatment patterns, biomarker testing, and outcomes in advanced NSCLC within the context of a large community oncology network. Outcomes of these community practice patients, although poor, were similar to those reported in 2nd-line clinical trials for relevant regimens. EGFR testing in community practice rose rapidly after 2010.     

紫杉醇脂质体治疗晚期非小细胞肺癌的临床观察

目的探讨紫杉醇脂质体联合顺铂治疗晚期非小细胞肺癌(NSCLC)的临床疗效及毒性反应。方法紫杉醇脂质体135 mg/m2加入5%葡萄糖注射液500 ml中,静脉滴入3 h,d1;DDP 25mg/m2加入生理盐水500 ml中,静脉滴入dl～d3。21～28 d为1周期。化疗2～4周期,观察近期临床疗效、不良反应。结果本组76例患者均完成2～4周期治疗,其中CR 3例,PR 33例,SD 34例,PD 6例,有效率(CR+PR)36例(47.37%),化疗后出现白细胞减少患者占100.0%(76/76),Ⅲ、Ⅳ度反应仅占21.05%(16/76);血红蛋白下降患者占28.94%(22/76);胃肠道反应占57.89%(44/76);疲乏无力发生率56.58%(43/76);脱发占15.79%(12/76)。结论紫杉醇脂质体联合顺铂治疗晚期NSCLC是一种疗效高,毒副作用可耐受的化疗方案。     

阿帕替尼联合培美曲塞治疗老年晚期非鳞非小细胞肺癌的疗效观察

  目的  观察培美曲塞与阿帕替尼联合用于老年晚期非鳞非小细胞肺癌的疗效。  方法  选取2016年1月到2017年6月在青岛市市立医院就诊的老年晚期非鳞非小细胞肺癌38例,均为一线或二线治疗失败者,入组人群要求年龄≥65岁、体力状况评分0~2分、预计生存期>3个月。将患者分为试验组（n=18）及对照组（n=20）。试验组行培美曲塞与阿帕替尼联合治疗,具体为:培美曲塞500 mg/m2 d1,阿帕替尼250 mg/d,d1~21,21d为1个治疗周期,对照组行单药培美曲塞,直到病情进展或不能耐受不良反应。该研究经青岛市市立医院医学伦理委员会审查批准。  结果  试验组和对照组的疾病控制率分别为72.2%和35%,具有统计学差异（χ2=5.265,P=0.022）;试验组和对照组的中位无进展生存期是5.7个月（95% CI:2.8~8.6）和3.1个月（95% CI:2.7~3.5）,两者比较差异有统计学意义（χ2=4.011,P=0.045）;发生手足综合征、高血压的比率有统计学差异（P=0.007,P=0.016）,多数为1~2级。  结论  培美曲塞与阿帕替尼联合用于老年晚期非鳞非小细胞肺癌疗效明确,不良反应可控。      

培美曲塞联合铂类一线治疗晚期非鳞非小细胞肺癌的临床观察

背景与目的：晚期肺癌一线化疗有效率仅30%～40%,本研究旨在探讨培美曲塞联合铂类药物(卡铂或顺铂)治疗晚期非鳞非小细胞肺癌(non-small cell lung cancer,NSCLC)的疗效及不良反应。方法：121例非鳞NSCLC患者,给予培美曲塞联合铂类化疗：培美曲塞500 mg/m2第1天,静脉滴注,卡铂300 mg/m2,第1天,静脉滴注,每3周重复;或培美曲塞500 mg/m2,第1天,静脉滴注,顺铂70 mg/m2,第1天,静脉滴注,每3周重复。上述方案连用2~6个周期,至少2个周期评价疗效。主要观察终点是疾病控制率(diseasecontrol rate,DCR),其次是中位无进展生存时间(progression-free survival,PFS)、1年生存率和安全性。结果：全组可评价疗效121例,完全缓解(complete response,CR)1例,部分缓解(partial response,PR)44例,病情稳定(stable disease,SD)50例,疾病进展(progressive disease,PD)26例,客观有效率(objective response rate,ORR)为37.2%(45/121),DCR为78.5%(95/121),PFS为5.2个月(95%CI：4.4~6.0个月),1年生存率为59.0%。其中培美曲塞联合卡铂组ORR为38.3%(23/60),DCR为78.3%(47/60),PFS为5.1个月(95%CI：3.8~6.4个月),1年生存率55.2%;培美曲塞联合顺铂组ORR为36.1%(22/61),DCR为78.7%(48/61),PFS为6.2个月(95%CI：4.3~8.1个月),1年生存率为62.5%。两组之间的ORR、DCR、PFS和1年生存率差异无统计学意义(P＞0.05)。主要不良反应为中性粒细胞和白细胞下降、乏力及胃肠道反应。结论：培美曲塞联合铂类药物一线治疗晚期非鳞NSCLC疗效确切,不良反应发生率低,耐受性较好。     

A phase II randomized trial evaluating gefitinib intercalated with pemetrexed/platinum chemotherapy or pemetrexed/platinum chemotherapy alone in unselected patients with advanced non-squamous non-small cell lung cancer

Current pemetrexed/platinum chemotherapy does not produce a satisfactory therapeutic response in advanced lung cancer patients. The aim of this study was to determine whether the administration of gefitinib, a tyrosine kinase inhibitor (TKI), intercalated with pemetrexed/platinum could improve the efficacy in chemotherapy-naïve patients with advanced non-squamous NSCLC without subsequent gefitinib maintenance therapy. Treatment-naïve patients with stage IIIB or IV NSCLC were randomly assigned to receive pemetrexed (500 mg/m² d1) and either cisplatin (75 mg/m² d1) or carboplatin (AUC = 5 d1) plus gefitinib (250 mg/d on days 3 to 16 of a 3-week cycle) (PC-G) or pemetrexed–platinum (PC) alone. Randomization was stratified according to the tobacco smoking status and EGFR mutational status of the patients. The primary endpoint was the non-progression rate (NPR) at 12 weeks. Secondary endpoints included progression-free survival (PFS), overall response rate (ORR), overall survival (OS), and biosafety. The NPR at 12 weeks was 84.5% for the PC-G treatment arm and 83.1% for the PC treatment arm (P = 0.87). Median PFS was 7.9 months for the PC-G arm and 7.0 months for the PC arm (P = 0.57). The ORR was 50.0% for the PC-G arm and 47.4% for the PC arm (P = 0.78). Median survival was 25.4 mo for the PC-G arm and 20.8 mo for the PC arm (P = 0.54). The incidence of adverse events was similar between the two treatment arms, except for a higher incidence of skin rash with PC-G. Predefined subgroup analyses demonstrated that PC-G significantly increased the PFS compared with the PC regimen in patients with EGFR mutations (P = 0.017). Although gefitinib intercalated with pemetrexed/platinum chemotherapy did not improve the NPR at 12 weeks compared with chemotherapy, an improvement in the PFS for the intercalated treatment arm was seen in the subgroup of patients with EGFR mutations.     

INP和AP方案三线治疗晚期非小细胞肺癌的近期疗效观察

目的 肺癌是全世界发病率及死亡率最高的恶性肿瘤.非小细胞肺癌(non-small cell lung cancer,NSCLC)约占肺癌的85％,＞2/3患者临床确诊时已处于中晚期.近年来晚期NSCLC治疗方法进步很大,但晚期NSCLC的三线治疗尚无标准方案.本研究回顾性分析比较异环磷酰胺(ifosfamide,IFO)、长春瑞滨(vinorelbine,NVB)及顺铂(cisplatin,DDP)组合的INP方案和培美曲塞(pemetrexed,PEM)联合DDP的AP方案三线治疗不可切除的局部晚期或Ⅳ期NSCLC的近期疗效及不良反应.方法 2013-04-01-2015-04-01江门市中心医院肿瘤科共收治经一、二线治疗失败的ⅢB期或Ⅳ期NSCLC患者158例,简单随机分配至INP组78例和AP组80例.2组患者的性别、年龄、ECOG评分、分期、吸烟状况及既往治疗方面均具有良好的可比性.INP组应用IFO 1.2 g/m2,静脉滴入,d1～d2;NVB 20 mg/m2,静脉推注,d1、d8;DDP 25 mg/m2,静脉滴入,d1～d3.AP组应用PEM 500 mg/m2,静脉滴入,d1;DDP 25 mg/m2,静脉滴入,d1～d3.治疗周期为21 d,共4个周期.每2及4个周期后复查CT,按RECIST标准评价疗效.无进展生存期(progression free survival,PFS)定义为首次治疗开始之日到疾病进展或患者死亡.结果 158例患者均可评价,中位随访期13个月.INP和AP组的客观缓解率分别为12.8％(10/78)和17.5％(14/80),x2=0.671,P=0.413;疾病控制率分别为53.8％(42/78)和57.5％(46/80),x2=0.214,P=0.644.PFS分别为153和189 d,差异有统计学意义,P=0.027.不良反应可耐受.INP组和AP组的白细胞减少分别为74.4％ (58/78)和37.5％ (30/80),差异有统计学意义,P＜0.001;中性粒细胞减少分别为64.1％ (50/78)和37.5％ (30/80),差异有统计学意义,P=0.001;血小板减少分别为30.8 ％(24/78)和40.0％(32/80),P=0.225;贫血分别为59.0％(46/78)和52.5％(42/80),P=0.413;恶心呕吐分别为79.5％(62/78)和55.0％ (44/80),差异有统计学意义,P=0.001;周围神经毒性分别为64.1％ (50/78)和37.5％(30/80),差异有统计学意义,P=0.001;静脉炎分别为25.6％(20/78)和2.5％(2/80),差异有统计学意义,P＜0.001.INP组独有的不良反应尿路刺激征发生率为12.8％(10/78).血液学及非血液学毒性INP方案明显高于AP方案,P＜0.05.结论 INP组和AP组三线治疗晚期NSCLC的疗效相似;但后者的中位PFS较长,且不良反应明显减轻.患者经济奈件允许的情况下,三线化疗,尤其是肺腺癌患者,推荐AP方案.     

多西他赛或表皮生长因子受体酪氨酸激酶抑制剂二线治疗晚期非小细胞肺癌的临床观察

目的 观察多西他赛或表皮生长因子受体酪氨酸激酶抑制剂（epidermal growth factor receptor tyrosine kinase inhibitors,EGFR-TKIs）二线治疗晚期非小细胞肺癌（non-small cell lung cancer,NSCLC）的临床疗效及安全性。 方法 回顾性分析2009年1月至2013年6月接受多西他赛或EGFR-TKIs二线治疗晚期NSCLC患者的临床资料,对符合入组标准的100例进行观察和分析,其中52例接受EGFR-TKIs治疗（TKIs组）,48例接受多西他赛治疗（DOC组）。采用Kaplan-Meier方法计算两组患者的中位无疾病进展生存时间（mPFS） 、中位总生存时间（mOS）,并行Log-rank检验。结果 TKIs组、DOC组患者二线治疗后mPFS分别为6个月、3个月（P=0.021）;mOS分别为16个月、10个月（P=0.068）;客观有效率（ORR）分别为23.1％、6.3％（P=0.038）。DOC组Ⅲ~Ⅳ级白细胞减少、中性粒细胞减少及其引起发热的发生率明显高于TKIs组（P均＜0.001）。结论 临床上对具有EGFR敏感突变潜在临床特征的晚期NSCLC患者进行二线治疗时,EGFR-TKIs比多西他赛治疗能显著延长患者中位无疾病进展生存时间,毒副反应较少,具有更高的安全性。     

Clinical prognostic model for older patients with advanced non-small cell lung cancer

BackgroundOlder patients with non-small cell lung cancer (NSCLC) are often not prescribed standard therapy. It is important to know which older patients would be candidates for aggressive therapy based on their prognosis, and to develop a model that can help determine prognosis.MethodsData on older patients (≥70 years) enrolled on 38 NCI cooperative group trials of advanced NSCLC from 1991 to 2011 were analyzed. Multivariable Cox PH model was built with a stepwise selection. We derived a prognostic score using the estimated Cox PH regression coefficient. We then calculated the area under receiver operating characteristic (ROC) curve of survival in the testing set.ResultsThe final analysis included 1467 patients, who were randomly divided into a training (n = 963) and a testing set (n = 504). The prognostic risk score was calculated as: 3 (if male) + 3 (if PS = 1) + 8 (if PS = 2) + 11 (if initial stage = IV) + 4 (if weight loss). Patients were classified into two prognostic groups: good (0–8) and poor (≥9). The median survival in the two groups in the testing set were 13.15 (95% CI, 10.82–15.91) and 8.52 months (95% CI, 7.5–9.63), respectively. The model had area under the 1-year and 2-year ROCs (0.6 and 0.65, respectively) that were higher than existing models.ConclusionsMale gender, poor performance status, distant metastases and recent weight loss predict for poor overall survival (OS) in older patients with advanced NSCLC. This study proposes a simple prognostic model for older adults with advanced NSCLC.     

KRAS突变非小细胞肺癌的生物学和治疗研究进展

KRAS突变是非小细胞肺癌(NSCLC)最为常见的驱动基因突变之一。KRAS突变NSCLC具有高度异质性,多种突变亚型和不同共突变特征均影响其生物学行为和治疗应答。KRAS突变NSCLC是免疫治疗相对获益人群,而KRAS突变对化疗存在的影响仍存有争议。KRAS突变肺癌多年来遵循无驱动基因突变NSCLC的治疗方案。随着KRASG12C抑制剂的问世,该人群的靶向治疗已取得初步进展,联合治疗的效果在临床前和早期临床研究中初见成效。现就KRAS突变NSCLC的生物学和临床特征及治疗研究进展进行综述。     

晚期非小细胞肺癌患者癌症相关性乏力的临床观察

目的:评估晚期非小细胞肺癌(non-small cell lungcancer,NSCLC)患者癌症相关性乏力的发生情况及其与化疗之间的相互关系。方法:应用疲乏数字等级量表评估本院2009年1月—2009年12月120例晚期NSCLC患者的乏力指数。所有患者均完成4个疗程含铂双药联合化疗及为期1年的随访。化疗前、每2个疗程化疗后以及随访期间评估乏力指数。结果:120例晚期NSCLC患者中,轻度乏力29例(24.2%),中度乏力64例(53.3%),重度乏力27例(22.5%)。化疗期间,平均乏力指数呈进行性升高,4个疗程化疗结束时达最高值5.31;随访期间,乏力指数呈下降趋势,随访6个月时平均乏力指数降至最低值3.95。美国东部肿瘤协作组体能状况评分与乏力相关(P<0.01),而年龄、性别、病理学类型和临床分期均与乏力指数无相关性。疾病稳定(4.26±2.27和3.64±1.75)与部分缓解(4.27±2.28和2.33±1.50)患者在随访3个月时的乏力指数较化疗前下降,疾病进展患者随访3个月时的乏力指数较化疗前升高(4.48±2.09和5.00±1.75),差异均有统计学意义(P<0.01)。结论:癌症相关性乏力在晚期NSCLC患者中的发生率较高,化疗可加重乏力程度。体能状况和化疗疗效与乏力指数相关。     

多西他赛联合阿帕替尼二线治疗非鳞癌非小细胞肺癌的疗效观察

目的探讨非鳞癌非小细胞肺癌采用多西他赛联合阿帕替尼二线治疗的临床效果及不良反应。方法选取2015年5月至2018年5月间上海市第一人民医院宝山分院收治的120例非鳞癌非小细胞肺癌患者,根据治疗方式不同分为研究组和对照组,每组60例。对照组患者采用多西他赛治疗,研究组患者采用多西他赛联合阿帕替尼治疗,比较两组患者的治疗效果、不良反应发生概率、细胞角蛋白19片段(CYFRA21-1)、血管内皮生长因子(VEGF)、基质金属蛋白酶9(MMP-9)和癌胚抗原(CEA)水平变化、心理状态及生活质量情况。结果对照组患者客观反应率为40. 0%,低于研究组患者的71. 7%,差异有统计学意义(P <0. 05)。对照组患者骨髓抑制和胃肠道反应发生率低于研究组患者,差异均有统计学意义(均P <0. 05)。治疗前,两组患者的CYFRA21-1、VEGF、MMP-9及CEA水平比较,差异无统计学意义(P>0. 05)。治疗后,两组患者上述指标均低于治疗前,且研究组患者均低于对照组,差异均有统计学意义(均P <0. 05)。治疗前,两组患者抑郁自评量表(SDS)和焦虑自评量表(SAS)评分比较,差异无统计学意义(P>0. 05)。治疗后,研究组患者的SDS和SAS评分均低于对照组,差异均有统计学意义(均P <0. 05)。治疗前,两组患者生活质量比较,差异无统计学意义(P>0. 05)。治疗后,研究组患者生活质量各评分均高于对照组患者,差异均有统计学意义(均P <0. 05)。结论多西他赛联合阿帕替尼治疗非鳞癌非小细胞肺癌患者效果确切,可在临床上进一步广泛推广与应用。     

Treatment of patients with advanced non-small cell lung cancer

In advanced non-small cell lung cancer (NSCLC), an objective response to chemotherapy is of limited value and the impact of chemotherapy on survival is modest. Therefore, endpoints evaluating the patients’ subjective benefit such as symptom control (SC), quality of life (QOL) or clinical benefit (CB) have recently been implemented into clinical trials, mostly as secondary endpoints. Chemotherapy offers SC, not only in patients with an objective response, but also in a proportion of patients with disease stabilization. For this purpose, three to four cycles of platinum-based chemotherapy are recommended. Interpretation of QOL objectives is limited by several methodologic problems. Studies comparing best supportive care alone with either older platinum-based combinations or single-agent chemotherapy with a new cytotoxic drug usually indicate improved survival and improvement of some component(s) of QOL in the active treatment arm. However, results from studies comparing different chemotherapies are less definitive. Trials comparing single-agent therapy with a new drug with new combinations mostly report no difference in QOL. In addition, most trials comparing new platinum-based combinations with older ones, and trials comparing new platinum-based regimens fail to show any differences in QOL. As a whole, it is far from clear whether combination therapy is superior to modern single-agent therapy, when the patient’s benefit is the primary endpoint. Non-platinum-based doublets, compared with platinum-based doublets, may lead to slightly inferior survival, are not always less toxic, and have not been proven to provide better QOL outcomes. The CB response, originally reported in pancreatic cancer, measures more than SC, but not full QOL. Encouraging experience with this tool was reported in advanced NSCLC. Randomized studies designed to look at some form of patient benefit as a primary endpoint should be a priority in advanced NSCLC.     

Chemotherapy in elderly patients with advanced non-small cell lung cancer

Because of increasing life expectancy and of higher risk of cancer with ageing, lung cancer in elderly is a frequent disease. For a long time nihilism influenced treatment decisions in elderly patients with advanced non-small cell lung cancer. Since the beginning of the last decade single agent chemotherapy has been accepted as standard of care, vinorelbine and gemcitabine being the most frequently used drugs in Europe and US, docetaxel in Japan.Platinum-based doublets have been shown to be superior to monotherapy in young and fit patients with advanced non-small cell lung cancer. Although there were some indications from subgroup analyses of clinical trials not specifically dedicated to elderly patients that a platinum-based doublet might also benefit to older patients, there was no definitive proof of concept until ASCO meeting 2010. At this meeting results of a phase 3 trial showed that PS 0-2 patients, aged 70-89 years drove a significant benefit from a treatment with carboplatin associated to weekly paclitaxel compared to a monotherapy. Thus, the paradigm of treatment in elderly patients should perhaps be modified from a single agent to doublet chemotherapy. Whether other platinum-based doublets would provide the same benefit as the specific one studied remains to be evaluated.     

局部晚期非鳞非小细胞肺癌同步放化疗两种方案比较研究

目的 比较两种方案治疗局部晚期非鳞非小细胞肺癌副反应及近期疗效。方法 回顾2009年3月—2013年1月42例局部晚期非鳞非小细胞肺癌患者,所有患者均接受同步放化疗,A组放疗同步培美曲塞+顺铂化疗,B组放疗同步多西他赛+顺铂化疗,比较A、B两组患者副反应及近期疗效。结果 A组28例患者,B组14例患者,两组副反应比较,血液毒性:白细胞减少、中性粒细胞减少、血色素降低、血小板减少无统计学差异(P＞0.05)。非血液毒性:放射性肺损伤发生率、咳嗽发生率B组明显高于A组,有统计学差异(P＜0.05)。而其他非血液毒性:肝功能损伤、肾功能损伤、发热、呼吸困难、放射性食管炎、乏力、体重下降、消化道反应、皮肤反应均无统计学差异(P＞0.05)。近期疗效:A、B两组有效率分别为75%及71.43%,无统计学差异(P＞0.05)。结论 放疗同步培美曲塞+顺铂化疗与同步多西他塞+顺铂化疗的两组疗效无显著差异,但培美曲塞在治疗局部晚期非鳞非小细胞肺癌副反应方面存在一定优势。     

Clinical outcomes with pemetrexed-based systemic therapies in RET-rearranged lung cancers

BackgroundRET rearrangements are targetable, oncogenic lung cancer drivers. While previous series have shown durable clinical benefit with pemetrexed-based therapies in ALK- and ROS1-rearranged lung cancers, the benefits of pemetrexed-based treatments in patients with RET-rearranged lung cancers relative to other genomic subsets have not previously been explored.Patients and methodsA retrospective review of patients with pathologically confirmed stage IIIB/IV lung adenocarcinomas and evidence of a RET, ROS1, or ALK rearrangement, or a KRAS mutation was conducted. Patients were eligible if they received treatment with pemetrexed alone or in combination. The primary outcome of progression-free survival (PFS), and secondary outcomes of overall response rate (ORR, RECIST v1.1), time to progression (TTP), and time to treatment discontinuation were compared between RET-rearranged and groups of ROS1-rearranged, ALK-rearranged, and KRAS-mutant lung cancers.ResultsWe evaluated 104 patients. Patients with RET-rearranged lung cancers (n = 18) had a median PFS of 19 months [95% confidence interval (CI) 12–not reached (NR)] that was comparable with patients with ROS1- (23 months, 95% CI 14–NR, n = 10) and ALK-rearranged (19 months, 95% CI 15–36, n = 36) lung cancers, and significantly improved compared with patients with KRAS-mutant lung cancers (6 months, 95% CI 5–9, P < 0.001, n = 40). ORR (45%), median TTP (20 months, 95% CI 17–NR), and median time to treatment discontinuation (21 months, 95% CI 6–NR) in patients with RET-rearranged lung cancers were not significantly different compared with patients with ALK- and ROS1-rearranged lung cancers, and improved compared with patients with KRAS-mutant lung cancers.ConclusionDurable benefits with pemetrexed-based therapies in RET-rearranged lung cancers are comparable with ALK- and ROS1-rearranged lung cancers. When selecting therapies for patients with RET-rearranged lung cancers, pemetrexed-containing regimens should be considered.     

贝伐珠单抗联合化疗对复治晚期非鳞非小细胞肺癌患者的疗效及预后分析

  目的  探讨贝伐珠单抗联合化疗对复治晚期非鳞非小细胞肺癌（non-squamous non-small cell lung cancer,NSNSCLC）患者的疗效和安全性,分析影响预后的因素。  方法  回顾性分析2013年2月至2017年6月北京胸科医院收治的41例复治晚期NSN? SCLC患者的病例资料。其中腺癌38例,其他病理类型3例。19例患者为二线治疗,22例患者为二线以上治疗。表皮生长因子受体（epidermal growth factor receptor,EGFR）突变阳性18例,突变阴性23例。评价贝伐珠单抗联合化疗的疗效和安全性,对可能影响预后的因素进行单因素和多因素分析。  结果  所有患者均接受化疗联合贝伐珠单抗的治疗,化疗的平均周期数为3.1个,贝伐珠单抗治疗的平均周期数为5.0个。41例患者均可评价疗效。全组患者客观缓解率（objective response rate,ORR）为12.2%,疾病控制率（disease control rate,DCR）为82.9%。二线治疗与二线以上治疗的患者疗效接近,ORR分别为10.5%、13.6%（P=0.572）,DCR分别为89.5%和77.3%（P=0.271）,差异无统计学意义。中位无进展生存期（progression-free survival,PFS）和中位总生存期（overall survival,OS）分别为4.6个月（95%CI:3.619~5.581）、11.9个月（95%CI:9.797~14.003）。单因素分析提示EGFR突变、贝伐珠单抗治疗周期数 > 4个及女性患者获得更长的生存（χ2=19.673,P < 0.001;χ2=6.820,P=0.009;χ2=6.374,P=0.012）。多因素分析显示,EGFR突变状态、贝伐珠单抗治疗周期数为影响患者预后的独立危险因素（HR=0.129,P=0.001;HR=0.336,P=0.012）。常见的不良反应有骨髓抑制、出血、高血压、蛋白尿等,多数为1~2级。  结论  贝伐珠单抗联合化疗对复治晚期NSNSCLC患者疗效确切,不良反应可耐受,EGFR突变阳性、贝伐珠单抗使用4个周期以上的患者预后较好。