非小细胞肺癌术后辅助化疗的共识

近年来有关非小细胞肺癌术后辅助化疗的治疗标准发生了显著变化,越来越多的前赡性、大样本随机临床试验和多项荟萃分析均证实辅助化疗,特别是新一代化疗药物的含铂联合方案能显著提高化疗反应和总体生存期,降低死亡危险比,且毒性反应均可耐受.因此,对于完整手术后的非小细胞肺癌,特别是Ⅰ B～Ⅱ期的患者采用辅助化疔是合理治疗方案.     

Ⅰb～Ⅲa期非小细胞肺癌术后辅助化疗的进展

肺癌是危害人民生命健康的常见恶性肿瘤,其发病率及死亡率居我国大中城市肿瘤之首位,也是世界人类的最主要死亡原因。由于肺癌患者发病 年龄较大,常合并多器官系统疾病,且肺叶或全肺切 除术后对化疗耐受性差,再加之早期关于术后辅助 化疗临床研究成功的报道不多,因而对非小细胞肺 癌(NSCLC)的术后辅助化疗一直存在争议。本文 通过对近年来国际间几项重要的术后辅助化疗研究 的剖析并结合2004年美国临床肿瘤年会(ASCO)公 布的最新研究进展,以期为我国肺癌临床实践给予正确的引导。     

非小细胞肺癌术后辅助化疗的探讨

非小细胞肺癌手术后有1/3～1/2病人复发、转移,手术后辅助化疗是令人关注的问题.自20世纪60年代起人们就在这一领域进行尝试,但一直未获得期望的结果.1995年英国医学杂志发表了第一篇有关问题的Meta分析结果,术后用含顺铂的联合化疗方案有延长远期生存的趋势.近年来陆续发表的前瞻性随机临床研究显示对术后早期非小细胞肺癌,特别是IB期病人使用含铂类药物方案化疗可以延长远期生存,但根据统计学要求,目前所积累的临床资料样本量尚不能做出最后结论.     

Ⅲ期非小细胞肺癌新辅助化疗疗效分析

目的：探讨Ⅲ期非小细胞肺癌(NSCLC)新辅助化疗的可行性及毒性反应并评价其有效性。方法：对2001年1月～2002年10月89例病例进行回顾性研究，其中新辅助化疗组37例，对照组52例。试验组给予术前NVB DDP化疗两周期，对照组则直接行手术治疗。结果：新辅助化疗组有效率为75．67％(28／37)，病期下调率为43．24％(16／37)，手术切除率为97．22％，对照组切除率为92．30％，两组手术失血量，手术并发症和手术死亡率均无显著性差异。结论：术前新辅助化疗安全、有效，能降低Ⅲ期非小细胞肺癌的病期，有助于提高手术切除率。     

非小细胞肺癌辅助化疗研究进展

近年来,非小细胞肺癌(NSCLC)术后辅助化疗的Ⅲ期随机临床试验结果已陆续报道,术后辅助化疗逐渐被接受,已成为Ⅱ～ⅢA期非小细胞肺癌综合治疗的重要措施之一.本文就NSCLCⅢ期随机临床试验结果作一综述.     

辅助化疗治疗Ⅲ期非小细胞肺癌的临床研究

辅助化疗在治疗Ⅲ期非小细胞肺癌中的应用仍有较多争议 ,其疗效国内外各家报道不一。自 1995～ 2 0 0 0年间 ,作者对 6 9例术前诊断为Ⅲ期非小细胞肺癌的患者进行了随机对照研究 ,旨在探讨辅助化疗在提高Ⅲ期非小细胞肺癌的手术切除率、改善患者的长期生存率和生存质量。1　材料与方法1.1　分组方法　 ( 1)术前经细胞学或病理学确诊的Ⅲa或Ⅲb期NSCLC ;( 2 )年龄 2 0～ 70岁 ;( 3)入组前未经过放、化疗 ;( 4)Karnofsky评分均在 80以上 ,能接受手术治疗者 ;( 5 )愿意接受术前化疗者。凡在纳入标准以外的患者均不能进入实验组或对照组。用…     

非小细胞肺癌术后辅助化疗现状与展望

 非小细胞肺癌（NSCLC）术后辅助化疗出现于20世纪70年代，随着各种新药及新的联合化疗方案的出现，NSCLC的术后辅助化疗亦在不断地进展，越来越多的证据显示术后辅助化疗能提高NSCLC患者的生存期生活质量，就NSCLC的术后辅助化疗现状进行了介绍并对其发展前景进展的展望。     

非小细胞肺癌术后辅助化疗的临床研究

背景与目的 非小细胞肺癌术后辅助化疗一直是国内外的研究热点。本研究的目的是对比观察术后辅助化疗对非小细胞肺癌患者生存期的作用。方法 2000年6月～2003年12月，观察64例ⅠB～ⅢA期行完全性切除的非小细胞肺癌患者，包括接受术后长春瑞滨＋顺铂（NP）方案或紫杉醇＋卡铂（TP）方案化疗的化疗组和仅行术后观察的观察组，然后以Kaplan-Meier法对两组病例的1、2、3、4年生存率和中位生存时间进行分析。结果 化疗组的1、2、3、4年生存率分别为93．9％、84．6％、71．4％、58．4％，观察组分别为93．6％、83．1％、63．5％、43．1％，两组间3年和4年生存率差异均有统计学意义（P〈0．05）。化疗组与观察组中位生存时间分别为52个月和47个月（P〈0．05），无病生存时间分别为19个月和16个月（P〈0．05）。结论 术后含铂辅助化疗可以延长完全切除病灶的ⅠB～ⅢA期非小细胞肺癌患者的术后生存期。     

Ⅲ期非小细胞肺癌术后辅助化疗疗效分析

目的评价Ⅲ期非小细胞肺癌(NSCLC)切除术后辅助化疗疗效,并对影响术后辅助化疗的因素进行初步分析。方法回顾性分析本院268例切除术后的Ⅲ期NSCLC,有94例于术后3~4周开始接受化疗(辅助化疗组),其中予以CAP方案化疗42例;EP方案化疗34例;NP方案化疗18例。在化疗组中化疗3~4周期56例;化疗4~6周期38例。另174例患者术后未行化疗(单纯手术组)。结果辅助化疗组和单纯手术组的5年生存率分别为27.6%和16.6%(P<0.05),差别有统计学意义。在辅助化疗组中行CAP、EP、NP方案化疗组的5年生存率分别为26.1%、26.4%和27.7%(P>0.05),而在化疗组中化疗3~4周期和化疗5~6周期患者的5年生存率分别为26.7%和28.8%(P>0.05)。结论对切除术后Ⅲ期NSCLC患者进行3~4周期,以顺铂为基础的化疗方案的辅助化疗,可以提高长期生存率。     

Ⅱ期非小细胞肺癌术后辅助化疗疗效分析

目的 评价Ⅱ期非小细胞肺癌（NSCLC）术后辅助化疗疗效。方法 回顾性分析本院1991—2001年手术根治切除的429例Ⅱ期NSCLC的病例资料，其中231例辅助化疗组患者于术后4—5周开始接受以铂类为基础的化疗3—4周期，MVP方案治疗72例，CAP方案治疗89例，NP方案治疗70例，另单纯手术组198例。结果 ⅡA期单纯手术组和术后辅助化疗组的5年生存率分别是41．86％和48．96％（P〉0．05），无显著差异；MVP和CAP化疗方案的5年生存率分别为41．37％和44．44％，与单纯手术组相比，均无显著差异（P〉0．05），而NP组的5年生存率为63．33％，明显高于单纯手术组（P〈0．05）。ⅡB期两组的5年生存率分别为30．35％和42．96％（P〈0．05），差异有统计学意义；与ⅡA期类似，对比单纯手术组，MVP和CAP方案的5年生存率无显著提高（37．21％，37．74％，P〉0．05），而NP方案的5年生存率升高明显（55％，P〈0．05）。结论 3—4周期的NP方案术后辅助化疗能提高Ⅱ期非小细朐肺痛患者的牛存率。     

Adjuvant chemotherapy for non-small cell lung cancer

Nearly half of all patients who undergo surgical resection of localized non-small cell lung cancer (NSCLC) will develop and ultimately die of recurrent disease. The postoperative radiotherapy (PORT) meta-analysis showed adjuvant thoracic radiotherapy to have a detrimental effect on survival in this patient population. A meta-analysis of early trials of adjuvant chemotherapy by the Non-Small Cell Lung Cancer Collaborative Group showed that while chemotherapy with alkylating agents was also detrimental, chemotherapy with cisplatin-based adjuvant chemotherapy was associated with an improved hazard ratio for death (HR = 0.87), equating to a 5 percent survival benefit at 5 years. However, the result was not statistically significant (p = 0.08). Recently, results have been reported for several large Phase III trials of adjuvant chemotherapy which differed with respect to the stage of resected disease included, the type of chemotherapy used and the use of post-operative radiotherapy. Three trials (IALT, JBR 10, and ANITA) that utilized cisplatin-based doublets showed a significantly positive survival benefit of adjuvant chemotherapy in patients with Stage II-IIIA NSCLC. The magnitude of this benefit, which was suggested to be 4-5 percent at 5 years in the meta-analysis and by the IALT study, may be as large as 8-15 percent as indicated by more recent studies with modern platinum-based doublet chemotherapy. These data indicate that medically fit patients with resected Stage II-IIIA NSCLC should be offered adjuvant chemotherapy with a modern cisplatin-based doublet.     

Surgical adjuvant chemotherapy in non-small cell carcinoma of the lung

A review of the published clinical trials of surgical adjuvant chemotherapy in lung cancer indicated that in the majority of nonrandomized trials, conclusions favored the use of adjuvant chemotherapy. On the other hand, most randomized trials were unable to show any statistically significant difference in survival or disease-free interval between treated groups and controls. On the contrary, in several studies the survival was better in the control group. It was concluded that adjuvant chemotherapy has no place in the routine treatment of resectable lung cancer; however, further prospective controlled randomized trials are needed using new agents, new combinations, or new schedules.     

The Rationale for Adjuvant Chemotherapy in Stage I Non-small Cell Lung Cancer

The past decade has witnessed renewed interest in studies exploring the benefits of adjuvant (postoperative) chemotherapy (± radiation therapy) in patients with resected non-small cell lung cancer (NSCLC). Recently completed adjuvant trials have included a heterogeneous group of patients with resected stages I to IIIA NSCLC. With rare exception, the published results of these studies indicate adjuvant chemotherapy imparts a significant overall survival advantage. Subset analyses suggest survival benefit occurs primarily in patients with resected stage II or IIIA and is less likely to occur in stage I patients. This apparent lack of survival benefit in stage I patients was seemingly validated in a prospective trial conducted by the Cancer and Leukemia Group B in which stage IB patients were randomized to observation or adjuvant carboplatin and paclitaxel. Survival at 5 -years was identical in the two arms of this trial. By contrast, two contemporary postoperative chemotherapy trials also conducted exclusively in stage I NSCLC patients yielded positive survival results. The divergent outcome of the prospective trials along with the negative subset analyses has created uncertainty as to the utility of postoperative adjuvant chemotherapy in stage I NSCLC. Herein we review the data underlying this controversy and offer a proposed algorithm to aid the clinician in selecting patients whom we believe may benefit from adjuvant chemotherapy. The treatment algorithm is based on currently available tumor- and host-related factors that affect prognosis.     

Adjuvant immunotherapy for non-small cell lung cancer

Non-small cell lung cancer (NSCLC) is the biggest cancer killer in the United States and worldwide. In 2011, there are estimated to be 221,130 new cases of lung cancer in the United States. Over a million people will die of lung cancer worldwide this year alone. When possible, surgery to remove the tumor is the best treatment strategy for patients with NSCLC. However, even with adjuvant (postoperative) chemotherapy and radiation, more than 40% of patients will develop recurrences locally or systemically and ultimately succumb to their disease. Thus, there is an urgent need for developing superior approaches to treat patients who undergo surgery for NSCLC to eliminate residual disease that is likely responsible for these recurrences. Our group and others have been interested in using immunotherapy to augment the efficacy of current treatment strategies. Immunotherapy is very effective against minimal disease burden and small deposits of tumor cells that are accessible by the circulating immune cells. Therefore, this strategy may be ideally suited as an adjunct to surgery to seek and destroy microscopic tumor deposits that remain after surgery. This review describes the mechanistic underpinnings of immunotherapy and how it is currently being used to target residual disease and prevent postoperative recurrences after pulmonary resection in NSCLC.     

Ⅲ期非小细胞肺癌患者骨髓微转移与新辅助化疗及预后的关系

目的　研究Ⅲ期非小细胞肺癌患者骨髓中微转移与新辅助化疗及预后的关系。方法　选取Ⅲ期非小细胞肺癌患者 65例 ,随机分为新辅助化疗组 ( 3 2例 )及直接手术组 ( 3 3例 ) ,两组患者均于术中切取肋骨获得骨髓 ,应用RT PCR技术检测CK19mRNA及CEAmRNA的表达 ,并进一步分析两指标表达情况与生存期的关系。结果　新辅助化疗组及直接手术组患者骨髓中CK19阳性率分别为 18.8% ( 6/ 3 2 )、45 .5 % ( 15 /3 3 ) (P =0 .0 3 3 ) ,CEA阳性率分别为 2 5 .0 % ( 8/ 3 2 )、5 1.5 % ( 17/ 3 3 ) (P =0 .0 41)。CK19与CEA的表达具有正相关关系 (rs=0 .671,P <0 .0 0 1)。CK19及CEA共同阳性者化疗有效率为 0 % ( 0 / 5 ) ,共同阴性者为 5 6.5 % ( 13 / 2 3 ) (P =0 .0 44 )。CK19及CEA共同阳性者及共同阴性者中位生存期分别为 11和 2 7个月 (P =0 .0 0 0 6)。Cox模型分析提示 ,新辅助化疗组中化疗疗效、CK 19及CEA的阳性表达是影响患者预后的独立因素。无效的化疗较有效的化疗死亡风险增加 (P =0 .0 43 ) ,CEA及CK 19阳性表达者较阴性者死亡风险增加 (P =0 .0 2 1,P =0 .0 2 0 )。结论　新辅助化疗能降低Ⅲ期非小细胞肺癌患者骨髓微转移的发生率。骨髓微转移提示患者预后不良。     

介入性新辅助化疗治疗Ⅲ期非小细胞肺癌的临床病理学疗效观察

 目的　评价介入性 (支气管动脉灌注 ,BAI)新辅助化疗治疗Ⅲ期非小细胞肺癌 (NSCLC)的临床及病理组织学疗效。方法　 36例Ⅲ期NSCLC患者在接受 1～ 3个疗程的BAI化疗后手术 ,观察BAI化疗的临床疗效和病理组织学反应。结果　 36例患者BAI化疗后总有效率 (RR) 5 5 .6 %。给予 2～ 3个疗程BAI化疗的RR为 76 .2 % (16 /2 2 ) ,明显高于给予 1个疗程化疗的 2 8.6 % (4/14 ) (P <0 .0 5 )。术后病理学观察显示 ,接受 2～ 3个疗程BAI化疗的总的组织学有效率 (HRR)为 6 1.9% (13/2 1) ,明显高于接受1个疗程BAI化疗的HRR 2 3.1% (3/13) (P <0 .0 5 )。临床疗效与病理组织学疗效并不完全一致。结论介入性 (BAI)新辅助化疗治疗Ⅲ期NSCLC以 2～ 3个疗程的疗效为优。化疗效果应结合临床和病理组织学疗效共同评价。     

新辅助化疗对围手术期非小细胞肺癌患者的影响

目的 研究新辅助化疗(MVP)是否影响非小细胞肺癌患者围手术期的安全性。方法 所有患者化疗方案均为MVP，即丝裂霉素(MMC) 长春碱胺(VDS) 顺铂(DDP)。将接受2周期术前新辅助化疗、根治性手术和2次术后化疗的患者与接受同样手术和4次术后化疗的患者进行比较。结果 在107例符合要求的病例中，新辅助化疗组有66例，对照组有41例，两组在性别、年龄、肿瘤分期、病理类型上均无统计学差异。新辅助化疗组患者的手术时间(P=0．262)、术中失血量(P=0．704)、术中输血量(P=0．811)、输血总量(P=0．074)比对照组患者略高，术后总引流量(P=0．061)稍低，但其差异均无统计学意义。两组术后死亡率(P=0．674)和并发症：心律失常(P=0．608)、支气管胸膜瘘(P=0．378)、肺炎(P=0．622)、呼吸衰竭(P=0．285)的比较亦均无统计学意义。结论 新辅助化疗对非小细胞肺癌患者围手术期的安全性无显著影响。     

含铂两药方案治疗老年晚期非小细胞肺癌的临床分析

目的 评价老年晚期非小细胞肺癌（NSCLC）患者接受以铂类为基础的两药联合化疗的疗效及安全性。方法 回顾性分析2003年1月至2009年12月北京胸科医院肿瘤内科收治的晚期NSCLC患者115例,年龄≥65岁,均接受以铂类为基础的两药联合一线化疗。具体化疗方案为：顺铂50～60mg／m2或卡铂曲线下面积（AUC）4～5静滴,第1天;紫杉醇135～150mg／m2静滴3～4h,第1天;或长春瑞滨25mg／m2静滴6～10min,第1、8天;或吉西他滨1000mg／m2静滴30min,第1、8天。上述方案3～4周为1个周期。观察并随访治疗疗效及主要不良反应。结果 115例患者中,应用铂类联合紫杉醇方案化疗44例（38.3％）,联合吉西他滨方案31例（27.0％）,联合长春瑞滨方案40例（34.7％）。全组患者的有效率（RR）为26.1％,疾病控制率（DCR）为76.5％,中位无进展生存时间（PFS）为5.5个月,中位总生存时间（OS）为14.0个月,1、2年生存率分别为50％和15％。化疗相关不良反应主要为骨髓抑制,包括白细胞及血小板减少,对症处理后可恢复。按照不同年龄、方案、铂类药物及ECOG评分进行亚组分析,其中不同ECOG评分及铂类药物的中位PFS及OS差异有统计学意义（P＜0.05）。结论 以铂类为基础联合第3代细胞毒性药物的两药方案一线治疗一般状态较好的老年晚期NSCLC的疗效较好,毒副反应可以耐受。     

周剂量紫杉醇联合异环磷酰胺治疗晚期非小细胞肺癌23例

目的　评价周剂量紫杉醇与异环磷酰胺联合化疗治疗晚期非小细胞肺癌的疗效和安全性。方法　紫杉醇 5 0～ 65mg/m2 静脉滴注 ,第 1、8、15天 ,异环磷酰胺 1.3 g/m2 静脉注射 ,第 2～ 4天。每 2 8天重复 ,2～ 3周期为一疗程。使用紫杉醇前常规给予抗过敏等处理 ,异环磷酰胺使用后第 0、4、8小时给予美安解毒。结果　本组完全缓解 1例 ,部分缓解 8例 ,稳定 11例 ,进展 3例 ,总有效率为 3 9.1% ( 9/2 3 ) ,临床受益率为 87.0 % ( 2 0 /2 3 )。化疗后KPS评分显著提高 (P <0 .0 1)。随防 2 0例 ,中位生存期为 8.9月 ,1年生存率为40 % ( 8/2 0 )。全组毒性反应主要为血液学毒性和消化道反应 ,其中白细胞降低发生率为 69.6% ( 16/2 3 ) ,恶心呕吐发生率为 47.8% ( 11/2 3 )。结论　周剂量紫杉醇 +异环磷酰胺联合化疗对晚期非小细胞肺癌有较好的疗效 ,不良反应可耐受 ,安全性高 ,可在临床上推广应用。     

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.