同步放化疗治疗Ⅲ期非小细胞肺癌

背景与目的：同步放化疗是肿瘤综合治疗的一种新形式，它具有放化疗协同作用，提高局控和控制远处转移缩短疗程等优点，但毒副反应值得关注。本文旨在探讨同步放射治疗加化疗及序贯化疗加放射治疗Ⅲ期非小细胞肺癌的疗效.方法：62例Ⅲ朗非小细胞肺癌患者分成两组，序贯化疗加放射治疗（序贯化放组）31例，采用EP方案治疗2～4个周期，每4周为1个周期，完成后行常规放射治疗。同步放射治疗加化疗组（同步化放组）31例，采用EP方案化疗第一天开始行放射治疗，化疗两个周期：放射治疗总量DT60～70Gy，6～7周完成。结果：两组患者伞部完成治疗计划。同步化放组CR25．8％，PR51．6％，CR＋PR77．4％；序贯化放组CR19．4％，PR45．1％，CR＋PR65％一同步化放组中位乍存期为20．6个月，序贯化放组中位生存期为14．5个月，差异有显著性（P〈0．05）。1、2、3年生存率同步化放组为76．2％、42．5％、28．6％，序贯化放组为66．5％、23．2％、11．6％（x^2=6．76，P〈0．01）。结论：同步化放疗能延长中晚期非小细胞肺癌患者的中位生存期，提高患者的生存率。     

Vindesine-ifosfamide-platinum (VIP) induction chemotherapy in surgically staged IIIA-N2 non-small-cell lung cancer: A prospective study

Purpose: In the pioneer data from the Memorial-Sloan-Kettering group, preoperative mitomycin-C–vindesine–platinum (MVP) induction chemotherapy in N2-NSCLC was accompanied with substantial pulmonary toxicity. In this study, the efficacy and toxicity of three-drug VIP induction chemotherapy, the pathologic response in resection specimens, the early survival and relapse patterns are examined.Patients and methods: Between June 1995 and March 1997, 39 consecutive patients with pathology proven N2-NSCLC were treated with three cycles of VIP induction, followed by definitive locoregional treatment (resection and mediastinal dissection or radical radiotherapy). Several patients had unfavorable prognostic characteristics with respect to clinical and biological findings, tumor location and bulk of disease.Results: The response rate to chemotherapy was 59% (95% Confidence Interval 34–75). Twenty-three responding patients had radical locoregional treatment: radical radiotherapy in four, resection in 19. Downstaging was present in nine of the 19 resection specimens, with two pathologic complete responses. The median survival time (MST) of all patients is 19 months, with a projected two-year survival of 49%. In patients responsive to chemotherapy who received definitive local treatment, the MST is not yet reached, and the projected two-year survival is 57%. Relapses were mainly distant, with isolated brain relapse as a disturbing finding. The main toxicity's were leukopenia and vomiting, but they were manageable. In contrast with MVP, no severe pulmonary toxicity occurred.Conclusions: VIP is a suitable induction regimen for N2-NSCLC, demonstrating a good activity and very acceptable toxicity.     

Phase I trial of bi-weekly paclitaxel and gemcitabine as second-line therapy for patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy

A phase I study was conducted to evaluate the maximum tolerated dose, feasibility, and efficacy of biweekly-administered paclitaxel and gemcitabine in patients with non-small-cell lung cancer (NSCLC) who had prevously been treated with platinum-based chemotherapy. In a dose-escalation study, 18 patients, under 75 yr old, with unresectable NSCLC that had relapsed or was resistant after platinum-containing chemotherapy with performance status of 0–2 were enrolled. Patients were treated with paclitaxel and gemcitabine biweekly. The dose escalation levels of paclitaxel (mg/m²) at a fixed dose of gemcitabine 1000 mg/m² were 110 (level 1), 130 (level 2), 150 (level 3), and 170 (level 4), respectively. All patients were eligible for evaluation of toxicities. At level 4, one patient developed an infection with grade 3 neutropenia and two other patients developed severe neurotoxicity (over grade 3). Thus, the recommended dose for phase II was paclitaxel 150 mg/m² and gemcitabine 1000 mg/m² due to dose-limiting toxicities including neutropenia and peripheral neurotoxicity. Partial response was seen in 4 cases of the 18 assessable patients, with an overall response of 22%. Bi-weekly paclitaxel and gemcitabine is feasible and appears to be an efficacious combination chemotherapy as second-line chemotherapy in refractory and recurrent patients with NSCL C who had been previously exposed to platinum-containing chemotherapy.     

可手术非小细胞肺癌多学科治疗对预后因素的影响

背景与目的：肺癌为当前最常见的恶性肿瘤之一，其中非小细胞肺癌（NSCLC）占绝大多数，而且大部分在诊断时已属晚期，对Ⅲ期估计不能全部切除的NSCLC，通过新辅助化疗可以使原发肿瘤缩小，提高手术切除率，消灭微小转移，延长NSCLC患者的生存率。所以本文目的在于探讨先化疗后手术对NSCLC预后因素的影响。方法：回顾性收集我院1995年-1997年先化疗后手术的Ⅰ-Ⅲ期NSCLC住院病例98例，其中Ⅰ期35例、Ⅱ期21例、Ⅲ期42例，手术前先进行1和2周期化疗的分别为83例和15例，化疗方案为MVP、MOP或MAP等，化疗缓解率（RR），部分缓解（PR）45例，稳定（SD）53例，手术方式为肺叶切除或全肺切除，分站摘除所有肉眼可见的胸内淋巴结，手术病理提示鳞癌35例、腺癌48例、混合型9例、其他6例，术后化疗2—3个周期（1996年后Ⅰ期NSCLC术后未作化疗）。对先化疗后手术的98例NSCLC患者的临床资料，随访5年以上，运用Kaplan—Meier生存曲线分析，Log Rank检验和Cox多因素分析，对影响预后的因素进行单因素和多因素分析。结果：98例先化疗后手术NSCLC患者的中位随访时间为41．2月，其中36例存活，62例死亡。98例NSCLC患者的1年、3年、5年生存率分别是88．78％、49．63％、18．46％；Ⅰ、Ⅱ、Ⅲ期5年生存率分别为33．23％、20．26％、5．52％（P=0．0002）；N0、N1、N2组5年生存率分别为35．49％、19．08％、4．90％（P=0．0004）。先化疗后手术NSCLC总分期越晚预后越差；术前末次化疗距手术时间为1月内预后好；全肺切除较肺叶切除预后差；肺门固定较肺门活动预后差；胸内淋巴结（＋）预后差，N1较N0预后差，N2较N1预后更差；其它预后不良因素包括肿块侵犯大血管、脏器、胸壁、心包，术中出血量≥400ml，腺癌；化疗后肿块纤维化预后好。本组结果还显示：术前化疗2周期较术前化疗1周期预后好；肿瘤坏死和术后未行化疗者预后差。结论：影响先化疗后手术NSCLC患者的预后因素为：总分期、术前末次化疗距手术时间、术式、肺门活动度、胸内淋巴结、肿块侵犯部位、术中出血量、病理类型及肿瘤纤维化。术前化疗次数、肿瘤坏死和术后化疗亦可能是先化疗后手术NSCLC预后的影响因素。     

化疗加艾迪注射液治疗中晚期非小细胞肺癌的临床研究

目的 研究艾迪注射液配合化疗治疗中晚期非小细胞肺癌(NSCLC)的疗效.方法 将123例确诊为中晚期NSCLC的患者随机分为治疗组63例及对照组印例,均采用NP方案化疗,长春瑞滨(NVB)25mg/m2静脉滴注,第1、8天;顺铂(DDP)75mg/m2,分3 d使用并水化.治疗组另加艾迪注射液50ml静脉滴注,第1天至第10天.观察两组近期疗效、不良反应及生活质量.结果 治疗组63例中,CR5例,PR27例,NC15例,PD16例,总有效(CR+PR)率50.8%;对照组60例中,CR3例,PR18例,NC18例,PD21例,总有效率35.0%.主要不良反应为骨髓毒性及胃肠反应,均以治疗组为轻.治疗组生活质量较对照组明显改善,差异均有统计学意义(P＜0.05).结论 艾迪注射液配合NP方案治疗中晚期NSCLC较单纯NP方案可提高疗效,并能减轻不良反应,提高患者的生活质量.     

序贯、交替、巩固化疗对晚期非小细胞肺癌的价值

 含铂的两药联合化疗仍然是PS 0～1分晚期非小细胞肺癌（NSCLC）患者的一线标准治疗方案，晚期NSCLC一线治疗的缓解率仅为20 %～40 %，中位生存时间为8～10个月。为了提高治疗的疗效，不同方案组合化疗成为研究的热点，主要包括序贯化疗、轮替化疗和巩固化疗。对于PS 0～1分、能耐受毒副反应的患者，临床医师可以考虑含铂的联合化疗方案随后单药治疗。对于年龄较大、身体情况较差不能耐受含铂化疗的患者，临床医师可以考虑单药治疗随后用单药治疗的序贯给药方式。迄今为止没有一个临床试验可以证实交替化疗比标准化疗疗效好。在标准的4～6个周期一线化疗后，在能耐受毒副反应的情况下，巩固化疗可能为患者提高生存质量。     

吉西他滨加卡铂治疗晚期非小细胞肺癌

目的：观察吉西他滨(GEM)加卡铂(CBP)联合化疗治疗晚期非小细胞肺癌(NSCLC)的近期疗效及毒副作用。方法：27例Ⅲ～Ⅳ期NSCLC(初治10例，复治17例)，采用联合化疗：GEM1250mg／m^2，静脉滴注，第1、8天，CBP300mg／m^2，静脉滴注，第1天，21天为1个周期。结果：初治10例中CR PR 6例，有效率60％，复治17例中CR PR7例，有效率41．2％，总有效率44．4％，主要副作用为骨髓抑制。结论：GEM CBP联合化疗治疗晚期非小细胞肺癌疗效较好，毒副反应可耐受。     

不可切除Ⅲ A(N2)期非小细胞肺癌的术前化疗

目的探讨不能切除的ⅢA（N2）期非小细胞肺癌（NSCLC）的治疗方法。方法1999年1月至2002年12月,76例不可切除ⅢA（N2）期NSCLC患者接受诺维苯（NVB,25mg／m^23,第1,5天）加卡铂（300mg／m^2,第1天）2个周期的化疗,第二周期化疗后3周重新评估能否手术切除。对化疗效果达到部分有效（PR）或完全有效（CR）、估计能完全切除的64例患者行剖胸探查术;对化疗后评价为稳定（SD）和进展（PD）的12例患者行放疗。64例手术患者中,完全切除（肺叶或全肺切除加纵隔淋巴结清扫术,至少达到R3水平）56例,术后继续给予诺维苯加卡铂化疗2个周期;不完全切除8例,另加局部放疗。结果76例不可切除的ⅢA（N2）期NSCLC经诱导化疗后手术或放疗,中位生存期为18．6个月,1,2,3年生存率分别为64．2％、39．4％和25．6％。其中完全切除患者的中位生存期为28．2个月,1,2,3年生存率分别为70．4％、52．5％和38．6％。结论对不可切除的局部晚期NSCLC,如诱导化疗后可以手术,应首选外科治疗。     

Advanced gastric carcinoma successfully treated with TS-1 as neoadjuvant chemotherapy

We report a patient with advanced gastric carcinoma successfully treated with the novel oral fluoropyrimidine anticancer drug TS-1 as neoadjuvant chemotherapy. The patient was a 76-year-old man who had gastric cancer clinically diagnosed as N2T4, invading the pancreas, the duodenum, and the transverse colon. He was treated as an outpatient with TS-1, 120 mg, administered orally every day for 28 days, followed by 14 days' rest, as one course. Two courses resulted in a marked reduction of the tumor without severe toxicity. Subsequently, the patient underwent curative surgery consisting of distal gastrectomy with D2 lymph node dissection. No surgical complications were observed. On microscopic examination, a few tumor cells were detected in the ulcer scar of the resected stomach and in the regional lymph nodes. Our report is the first to demonstrate the advantages of TS-1 as neoadjuvant chemotherapy for the treatment of advanced gastric carcinoma. Received: July 6, 2000 / Accepted: October 4, 2000     

升荣胶囊联合化疗治疗中晚期非小细胞肺癌

目的 观察升荣胶囊联合化疗治疗对一线治疗无效的非小细胞肺癌(NSCLC)的疗效及不良反应.方法 应用升荣胶囊联合其他常用化疗药物组成的联合化疗方案治疗NSCLC 68例,观察其疗效与不良反应.结果 试验组近期缓解率89.2%,对照组70.1%;症状改善率:试验组81.5%,对照组为53.9%;白细胞下降率治疗组为29.0%,对照组为41.9%;血小板下降率治疗组为29.0%,对照组为48.4%;两组差异均有统计学意义(P＜0.05).结论 升荣胶囊与化疗药物联合治疗NSCLC能提高疗效,减轻化疗不良反应.     

神经内分泌分化在非小细胞肺癌新辅助化疗疗效中的价值

背景与目的：非小细胞肺癌预后较差，近期研究发现非小细胞忡癌中有部分含有神经内分泌（Nemoendocrine，NE）颗粒，目前对含有NE颗粒的非小细胞肺癌的化疗疗效国内外尚有争议。本工作综合应用电镜、免疫组化和影像学分析研究非小细胞肺癌伴神经内分泌分化与化疗疗效的关系。方法：对62例NSCLC患者进行含铂类方案1～2个疗程的新辅助化疗，通过影像学判定化疗疗效。然后进行手术治疗，术后标本用光镜观察其组织病理学疗效、电镜观察NE颗粒、免疫组化法检测NE标记（CgA、Syn）。结果：本组病例NE标记阳性29例，阴性33例，阳性率为46．8％。在影像学上：NE分化阳性患者中有10例部分缓解（PR），19例为无效（NR）；阴性患者中有5例为PR，28例为无效（NR），但统计学上差异无显著性（P=0．069）。在组织病理学上：NE分化阳性患者中有21例组织学有效；阴性患者中有10例达到组织学有效，NE分化阳性的NSCLC患者化疗后病理组织学疗效较阴性者好（P=0．023）。结论：NSCLC中NE分化阳性的患者对化疗较敏感。     

Phase II study of gemcitabine plus oxaliplatin as first-line chemotherapy for advanced non-small-cell lung cancer

This phase II study evaluated the response rate and tolerability of gemcitabine-oxaliplatin chemotherapy in non-small-cell lung cancer (NSCLC) patients. Chemonaive patients with stage IIIB or IV NSCLC received gemcitabine 1000 mg m(-2) on days 1 and 8, followed by oxaliplatin 130 mg m(-2) on day 1. Cycles were repeated every 21 days for up to six cycles. From February 2002 to May 2004, 60 patients were enrolled into the study in seven Italian institutions. We observed one complete response (1.7%) and 14 partial responses (23.3%), for an overall response rate of 25.0% (95% confidence interval, 14.7-37.9%). The median duration of response was 5.9 months (range 1.5-17.1 months). With a median follow-up of 6.7 months, median time to progressive disease and overall survival were 2.7 (range 1.9-3.4 months) and 7.3 months (range 7.2-8.6 months), respectively. The main grade 3-4 haematological toxicities were transient neutropenia in 11.7% and thrombocytopenia in 8.3% of the patients. Nausea/vomiting was the main grade 3-4 nonhaematological toxicity, occurring in 10.0% of the patients. Two (3.3%) patients developed grade 3 neurotoxicity. Our results show that gemcitabine-oxaliplatin chemotherapy is active and well tolerated in patients with advanced NSCLC, deserving further study, especially for patients not eligible to receive cisplatin.     

吉西他滨用于非小细胞肺癌治疗的研究进展

吉西他滨（健择,GEM）是治疗非小细胞肺癌（NSCLC）的有效新药。GEM＋顺铂联合化疗（GP方案）治疗晚期NSCLC的有效率31％－54％,中位生存期8．4－15．4个月,一年生存率30％－59％,化疗毒性反应可接受。GP方案可被认为是NSCLC 的标准化疗方案。GP方案21天与28天用药方法的疗效基本相同。随机对照研究GP方案的顺铂用药时序,GEM放射增敏,GEM与其他新药联合疗等问题值得进一步研究。     

A retrospective analysis of cisplatin,pemetrexed, and bevacizumab in previously treated non-small-cell lung cancer

Patients with non-small-cell lung cancer (NSCLC) often have an advanced disease when firstly diagnosed. Bevacizumab is a monoclonal antibody against vascular endothelial growth factor receptor (VEGFR). In this study, we retrospectively analyzed the efficacy of cisplatin, pemetrexed, and bevacizumab in previously treated advanced NSCLC. Results showed that the objective response rate(ORR) of this novel regimen is 43%, median progression-free survival (PFS) was 5.2 months (95% CI, 3.7 to 6.7 months) and median overall survival (OS) was 11.4 months (95% CI, 8.8 to 13.9 months). Adverse events were generally mild, ranging from grade 1 to grade 3. In conclusion, the combination of cisplatin, pemetrexed, and bevacizumab obtained promising results in selected patients with NSCLC. Randomized clinical trials are needed to further investigate the efficacy of this regimen.     

Comparing effectiveness with efficacy: outcomes of palliative chemotherapy for non-small-cell lung cancer in routine practice

Introduction

Randomized controlled trials (rcts) are the “gold standard” for establishing treatment efficacy; however, efficacy does not automatically translate to a comparable level of effectiveness in routine practice. Our objectives were to

• □ describe outcomes of palliative platinum-doublet chemotherapy (ppdc) in non-small-cell lung cancer (nsclc) in routine practice, in terms of survival and well-being; and
• □ compare the effectiveness of ppdc in routine practice with its efficacy in rcts.

Methods

Electronic treatment records were linked to the Ontario Cancer Registry to identify patients who underwent ppdc for nsclc at Ontario’s regional cancer centres between April 2008 and December 2011. At each visit to the cancer centre, a patient’s symptoms are recorded using the Edmonton Symptom Assessment System (esas). Score on the esas “well-being” item was used here as a proxy for quality of life (qol). Survival in the cohort was compared with survival in rcts, adjusting for differences in case mix. Changes in the esas score were measured 2 months after treatment start. The proportion of patients having improved or stable well-being was compared with the proportion having improved or stable qol in relevant rcts.

Results

We identified 906 patients with pre-ppdc esas records. Median survival was 31 weeks compared with 28–48 weeks in rcts. After accounting for deaths and cases lost to follow-up, we estimated that, at 2 months, 62% of the cohort had improved or stable well-being compared with 55%–63% who had improved or stable qol in rcts.

Conclusions

The effectiveness of ppdc for nsclc in routine practice in Ontario is consistent with its efficacy in rcts, both in terms of survival and improvement in well-being.     

晚期非小细胞肺癌的维持化疗

维持化疗对晚期非小细胞肺癌(NSCLC)可延长生存期.诱导化疗方案中证实有效的药物可用于维持化疗,二线、三线化疗药物及分子靶向药物似乎更适合用于晚期NSCLC维持化疗.     

吉西他滨联合顺铂治疗晚期非小细胞肺癌的临床观察

目的：总结西宁地区（海拔2260m）盐酸吉西他滨联合顺铂化疗方案治疗晚期非小细胞肺癌（NSCLC）的疗效及不良反应。方法：我科30例Ⅲ、Ⅳ期非小细胞肺癌患者，应用GP方案盐酸吉西他滨t250mg／m2（d，8）于60rain内静脉滴注，顺铂30mg／m2（d1-2）静脉滴注，21d为1周期，治疗2个周期后评价疗效。结果：CR0例，PR14例，sD8例，PD8例，总有效率（PR＋CR）为46．7％（14／30）；不良反应为白细胞、血小板下降和恶心、呕吐，但均可耐受。结论：高海拔地区应用盐酸吉西他滨联合顺铂方案，治疗晚期非小细胞肺癌有较好的疗效，且不良反应可以耐受。     

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。     

一线序贯应用厄洛替尼与化疗治疗晚期非小细胞肺癌的临床研究

 目的　评价化疗后序贯给予厄洛替尼在一线治疗非小细胞肺癌（NSCLC）中的客观缓解率和不良反应。方法　23例PS 0～1分的ⅢB～Ⅳ期NSCLC患者一线接受GC化疗方案（吉西他滨1250 mg／m2 第1、8天,顺铂75 mg／m2 第1天或卡铂AUC＝5第1天）,并序贯给予厄洛替尼（150 mg,第15天至第28天）,每28 d为1个周期,观察患者的客观疗效及不良反应。结果　23例患者接受95个周期的化疗,所有患者均可评价疗效。完全缓解（CR）0例,部分缓解（PR）7例（30.4 %）,疾病稳定（SD）14例（60.9 %）,疾病进展（PD）2 例（8.7 %）;总体客观缓解（RR）30.4 %,疾病控制（DCR ）91.3 %。Ⅲ度以上不良反应为白细胞减少3例（13.0 %）,皮疹2例（8.7 %）,恶心呕吐、血小板减少各2例（8.7 %）,没有出现治疗相关的间质性肺病。结论　GC化疗方案序贯厄洛替尼治疗模式的近期疗效较好,不良反应在患者可耐受范围内,远期疗效有待进一步观察。     

吉西他滨治疗高龄晚期非小细胞肺癌

目的:观察吉西他滨治疗高龄晚期非小细胞肺癌的疗效,并与同期单纯支持治疗的患者比较,以探讨高龄晚期非小细胞肺癌的治疗方案。方法:吉西他滨组21例,采用吉西他滨单药化疗,剂量为1250mg/m2,静脉滴注,第1、8天用药,每21天为1周期,共4周期。对照组23例不用任何化疗,单纯支持对症治疗。结果:吉西他滨组总有效率为28.6%,其中PR6例,SD12例,PD3例。对照组无CR和PR者。吉西他滨组中位缓解期6.3个月。吉西他滨组和对照组中位肿瘤进展时间分别为5.8和2.6个月,中位生存时间分别为12.8和4.6个月(P<0.01);1年生存率分别为46.6%和9.2%(P<0.01)。吉西他滨组KPS、体重增加和临床症状改善情况均显著高于对照组(P<0.01)。毒副反应方面吉西他滨组12例(57.1%)出现Ⅰ、Ⅱ级血小板减少,7例(33.3%)出现Ⅰ、Ⅱ级白细胞下降,未见Ⅲ、Ⅳ级毒性反应。少数患者血红蛋白下降Ⅰ度,恶心呕吐Ⅰ/Ⅱ度。结论:吉西他滨单药治疗高龄晚期非小细胞肺癌是安全有效的。