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。     

肺癌神经内分泌分化与术后生存关系探讨

目的 探讨非小细胞肺癌神经内分泌(NSCLC—NE)分化与患者手术后生存关系。方法 收集1997年4月至1999年4月98例肺癌手术切除病理标本，采用免疫组化标记特异性烯醇化酶(NSE)及突触素(SY)，并按强弱区分为“ 、 、 ”。对同一手术病例标本采用电镜观察特异性NE颗粒。术后病例随访36月，最长60月。采用Cox多因素风险模型分析NSCLC-NE分化与患者术后生存的关系。结果 91例为非小细胞肺癌。非小细胞肺癌NF阳性表达率为63．7％(58/91)，其中NSE阳性表达54例(59．3％)，SY阳性表达22例(24．1％)，电镜观察NE持异性颗粒30例(33．0%)。结合免疫组化和电镜观察，NSCLC-NE分化44例(48．4％)。Cox模型多因素分析结果表明NSCLC-NE分化者术后生存时间明显缩短(P=0.048)。术后生存与肺癌细胞分化程度(P=0．006)、病理分期(P=0．001)、NE表达强弱(P=0．054)有密切关系。结论 NSCLC-NE分化与肿瘤细胞分化和患者术后生存有关。采用NE标志物标记肿瘤，并观察其强弱改变．对术后评估具有较重要的参考意义，可作为为临床判断患者预后指标之一。     

国产紫杉醇及长春瑞宾联合铂类治疗晚期非小细胞肺癌的临床对照研究

目的　探讨国产紫杉醇及长春瑞宾加顺铂及卡铂联合方案对晚期非小细胞肺癌 (NSCLC)的疗效和毒副反应。方法　选取初治晚期NSCLC 181例 ,分别应用NP(长春瑞宾 +顺铂 )、TC(国产紫杉醇 +卡铂 )及TP(国产紫杉醇 +顺铂 )方案治疗。每例均完成两周期化疗后评价疗效及毒副反应。结果　三组患者近期有效率分别为NP组 42 .4%,TC组 40 .3 %,TP组 43 .3 %,三组间有效率比较均无显著性差异 ( χ2 =0 .10 86,P >0 .0 5 )。NP组中位生存期为 8.4个月 ,TC组 9.4个月 ,TP组 8.9个月 (P >0 .0 5 )。NP组 1、2、3年生存率分别为 3 9.0 %、16.9%、5 .1%;TC组分别为 41.9%、2 1.0 %、6.5 %;TP组分别为 40 .0 %、18.3 %、5 .0 %,三组间比较无统计学差异 ( χ2 =0 .14 0 4,P >0 .0 5 )。三组毒副反应均以骨髓抑制、脱发及恶心呕吐为主 ,但均未影响治疗。三组病例均无化疗相关死亡发生。结论　NP、TC及TP联合方案是治疗晚期NSCLC有效且耐受性较好的方案     

SPARC expression and prognostic value in non-small cell lung cancer

Secreted protein,acidic and rich in cysteine(SPARC) is expressed in numerous types of tumors and is suggested to have prognostic value.Moreover,because of its strong affinity for albumin,and hence albumin-bound drugs,SPARC has increasingly become a focus for research.In this study,we aimed to determine SPARC expression in patients with non-small cell lung cancer(NSCLC) and investigate the association of SPARC with disease prognosis.Tissue microarrays were constructed with specimens from 105 patients with NSCLC treated at Sun Yat-sen University Cancer Center,and immunohistochemical analysis was performed on these tissue microarrays to assess SPARC expression.Our results showed that SPARC expression status did not significantly relate with age,gender,and tumor stage.However,SPARC was expressed more frequently in squamous cell carcinoma than in adenocarcinoma(75% vs.43.5%,P = 0.004).Patients with smoking history had higher SPARC expression than non-smokers(68.2% vs.33.3%,P = 0.002).In both univariate and multivariate analyses,SPARC was a prognostic factor of overall survival(HR = 0.32;95% CI:0.16-0.65) but not disease-free survival.Our study indicates that SPARC expression is higher in squamous cell carcinoma than in adenocarcinoma in NSCLC.Most notably,SPARC can be used as a prognostic factor for NSCLC.     

Vascular Invasion as An Independent Prognostic Indicator in Radically Resected Non-small Cell Lung Cancer

Objective： A retrospective study was performed to analyze the impact of vascular invasion on prognosis in a series of radically resected non-small cell lung cancer （NSCLC） and the subgroup of T1-4 nodal negative NSCLC patients. Methods： A total of 259 NSCLC patients who had undergone radical resection were entered into this study. Detailed clinical data including five-year survival were obtained for all the patients. The tumors were reviewed for the presence or absence of vascular invasion. Fisher＇s exact tests were used to assess the relationship between vascular invasion and other clinicopathological variables. Survival time was defined as the interval from the date of operation to either death from lung cancer or the last follow-up. Univariate analysis of survival curve was performed by the Kaplan-Meier method using the Log rank test. Multivariate survival analysis was carried out by Cox regression. P〈0.05 was considered statistically significant. Results： In 259 patients, 33 cases were diagnosed as having vascular invasion. The overall 5-year survival was 37.5%. Patients with vascular invasion had a median survival of 20 months compared with 43 months for those without vascular invasion （P〈0.01）. Multivariate analysis indicated that vascular invasion was a significant independent prognostic predictor for shortened cancer-related survival in the patients. The relative risk for cancer-related survival was 2.2-fold greater in patients with vascular invasion （95% CI： 1.45-3.32）. Subgroup analysis revealed that patients with vascular invasion had a 5-year survival of 11.1% compared with 57.1% for those without vascular invasion in the resected lung cancer patients at T1-4N0M0 （P=0.002）. Conclusion： Vascular invasion can serve as an independent prognostic factor in radically resected NSCLC.     

Association of ABCC2 polymorphisms with platinum-based chemotherapy response and severe toxicity in non-small cell lung cancer patients

Platinum-based chemotherapy is the most common treatment for non-small cell lung cancer (NSCLC), and expression levels of drug metabolism and transport proteins are correlated with its efficacy and toxicity. In this study, we investigated the association of three putative functional polymorphisms of ABCC2 (C-24T, G1249A, and C3972T) with tumor response and occurrence of the grade 3 or 4 toxicity in 445 patients with stage III and IV NSCLC treated with platinum-based chemotherapy. We determined the genotypes of these three polymorphisms by the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MassArray) method. We found that the common homozygotes of -24C was associated with a better treatment response (adjusted odds ratios [ORs], 1.84; 95% confidence interval [CI], 1.05-3.23; P = 0.032). Furthermore, patients with 3972T had increased risk of severe thrombocytopenia toxicity (adjusted OR, 2.43; 95% CI, 1.06-5.56; P = 0.034); and in female subgroup analyses, this variant was associated with significantly increased risk of overall toxicity (adjusted OR, 2.63; 95% CI, 1.17-5.95; P = 0.02), particularly of hematologic toxicity (adjusted OR, 3.80; 95% CI, 1.62-8.87; P = 0.002). Moreover, -24T/3972T haplotype was also associated with significantly increased risk of hematologic toxicity. Our results suggested that C-24T variants had an effect on treatment response and that C3972T had an effect on severe toxicities among platinum-treated non-small cell lung cancer patients.     

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.     

Oxaliplatin doublets in non-small cell lung cancer: a literature review

Nowadays cisplatin doublets are considered the gold-standard treatment in advanced non-small cell lung cancer (NSCLC) patients, but are often associated to poor toxicity profile. In the last years different schedules have been developed in order to improve the tolerability of these regimens. Carboplatin is gradually replacing cisplatin in clinical practice as well as in clinical trials even if it is still unclear whether it has an equivalent efficacy compared to cisplatin. Oxaliplatin, the trans-l oxalato platinum compound, showed encouraging antineoplastic activity and favourable toxicity profile in NSCLC, but confirmatory randomized phase III trials are warranted. We performed a literature search in order to better understand the possible role of oxaliplatin-based combinations in advanced NSCLC treatment strategies.     

Docetaxel and mitomycin as second-line treatment in advanced non-small cell lung cancer

Purpose: To evaluate the feasibility, toxicity and efficacy of the combination of docetaxel and mitomycin C as second-line chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). Patients and methods: Thirty-eight patients with histologically confirmed, locally advanced or metastatic NSCLC were included in this phase II trial. All patients had been previously treated with a platinum-based regimen. Treatment consisted of docetaxel (75 mg/m²) followed by mitomycin C (8 mg/m²) on day 1, every 21 days. Patients received a minimum of three courses unless progressive disease was detected. Results: A total of 190 courses of docetaxel-mitomycin C were administered (median five courses per patient). This combination was well tolerated with grade 3–4 toxicity experienced with the following frequency: neutropenia in five patients (13%), fatigue in four (11%), anaemia, thrombocytopenia, nausea/vomiting and peripheral neuropathy in one each (3%). Three of 38 patients had a partial response (8%, 95% confidence interval 2.6–21.6%), 14 patients (37%) experienced stabilization of disease and 21 (55%) had disease progression. Median time to progression was 3.6 months. Overall median survival was 10.4 months, with the 1-year actuarial survival rate being 35%. Conclusions: The addition of mitomycin C to docetaxel as second-line therapy in NSCLC is well tolerated but does not seem to improve the response rate.     

康莱特联合化疗治疗中晚期非小细胞肺癌

背景与目的 化疗是中晚期非小细胞肺癌常用的治疗方法，但化疗有效率较低，约20％～50％，而且存在较为严重的副作用。为提高疗效，改善患者生活质量，降低毒副反应，本研究对康莱特联合化疗和单纯化疗治疗中晚期非小细胞肺癌的疗效、毒副反应及对生存质量的影响进行了比较。方法 将100例患者随机分成两组。单纯化疗组（对照组）50例，采用GP方案：吉西他滨1000mg／m^3，第1、8天，顺铂80mg／m^3，第2天，3周为一周期。康莱特联合化疗组（康莱特组）50例，化疗方案同对照组，于每周期化疗第一天开始静脉滴注10％康莱特注射液200ml，连用10天。两周期治疗结束后对其近期疗效、毒副反应及生存质量进行评价。结果 康莱特组有效率为52％，对照组为32％，两组比较有显著性差异（X^2-4．04，P〈0．05）。两组疗后的生存质量有显著性差异（t=2．8，P〈0．05）。康莱特组的不良反应发生率低于对照组，且发生的程度较轻。结论 康莱特联合化疗能提高有效率，降低不良反应，改善患者的生存质量。     

羟基喜树碱联合异环磷酰胺治疗铂类耐药的非小细胞肺癌的临床研究

背景与目的肿瘤细胞对铂类药物的耐药是非小细胞肺癌化疗失败的重要因素之一。研究和探讨抑制或／和逆转肺癌多药耐药的有效药物和化疗方案是肺癌临床研究的热点课题。本研究的目的是比较羟基喜树碱(HCPT)联合异环磷酰胺(IFO)治疗铂类耐药的NSCLC的疗效和毒性反应。方法2002年6月至2003年12月，入组NSCLC69例，予滴注HCPT6～8mg／m^2，第1～5天，IFO1．2mg／m^2，第1～3天，异环磷酰胺使用后第0、4、8小时给予美安解毒。每21天为一周期。疗效及毒性评定按照WHO标准。结果53例可评价疗效，无完全缓解者，部分缓解6例，稳定21例，进展26例，总有效率为11．3％(6／53)，临床受益率为50．9％(27／53)。化疗后PS评分显著提高。所有63例患者均可评价毒性反应，主要表现为不同程度的骨髓抑制，其中白细胞降低发生率为85．5％(59／69)，Ⅲ Ⅳ度下降达17．3％(12／69)；Ⅲ度血小板下降为5．9％(4／69)，无Ⅳ度毒性；Ⅲ度血红蛋白下降5．9％(4／69)，无Ⅳ度毒性。脱发明显，达87．0％。结论羟基喜树碱联合异环磷酰胺治疗铂类耐药的NSCLC有效，不良反应可耐受，安全性高，患者可接受。     

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.     

改进的多西紫杉醇联合顺铂方案治疗晚期非小细胞肺癌的临床观察

目的目前临床上广泛应用多西紫杉醇联合顺铂作为晚期非小细胞肺癌（NSCLC）的一线化疗方案，但传统3wk方案毒副反应较大。因此本研究为比较多西紫杉醇联合顺铂改进的3wk方案与传统3wk方案治疗晚期NSCLC的疗效、毒副反应及1a生存率。方法68例经组织学或细胞学确诊的Ⅲb或Ⅳ期NSCLC病人，随机分为两组，分别接受改进方案（A组）和传统3wk方案（B组）化疗。A组：多西紫杉醇总剂量按75mg／m^2，分2次分别于d1、d8，静脉滴注；每天顺铂25mg／m^2，静脉滴注，dl-d3，每3wk重复；B组：多西紫杉醇75mg／m^2，静脉滴注，d1，顺铂用法同A组，每3wk重复。2周期后评价疗效与毒副反应，并随访la生存率。结果两组均无CR，A组PR10例，SD20例，PD4例，总有效率为29.4％；B组PR11例，SD20例，PD3例，总有效率为32.4％；A组1a生存率为38．2％，B组1a生存率为35.3％，两组疗效（P=0．793）及1a生存率（P=0．801）差异无显著性。中性粒细胞Ⅲ／Ⅳ度减少A组17．6％；B组47．1％，两组差异有显著性（P=0．010）。结论多西紫杉醇联合顺铂改进的3wk方案治疗NSCLC与传统3wk方案相比，疗效相似，但血液学毒性明显下降，耐受性好。     

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.     

多西他赛联合卡铂治疗晚期非小细胞肺癌的疗效

背景与目的 化疗是治疗晚期非小细胞肺癌的主要方法.本研究旨在分析多西他赛加卡铂治疗晚期非小细胞肺癌的疗效.方法 本组共治疗64例ⅢB、Ⅳ期非小细胞肺癌,采用多西他赛75 mg/m2静脉注射,第1天,卡铂AUC=5静脉注射,第2天.结果 全组总有效率CR PR为42.6%,临床获益率CR PR SD为68.9%,中位生存期14个月,1年生存率45.23%.初治病例1年生存率48.84%,中位生存期14个月;复治病例1年生存率37.89%,中位生存期12个月,两组之间差异有统计学意义(P=0.0233).ⅢB期病例1年生存率44.86%,中位生存期15个月;Ⅳ期病例1年生存率39.75%,中位生存期12个月,两组之间差异有统计学意义(P=0.0354).腺癌、鳞癌患者的疗效差异无统计学意义.主要毒副反应为粒细胞下降、乏力、恶心呕吐及脱发等.结论 多西他赛联合卡铂方案治疗晚期非小细胞肺癌疗效可靠,副反应轻微,可作为晚期非小细胞肺癌的一线和二线治疗方案.     

Ｅ-ｃａｄｈｅｒｉｎ在非小细胞肺癌中的表达及其与预后的关系

目的　探讨上皮细胞钙粘附蛋白（Ｅ-ｃａｄｈｅｒｉｎ）在非小细胞肺癌（ＮＳＣＬＣ）中的表达及其与预后的关系。方法 免疫组化法检测８０例ＮＳＣＬＣ组织及１０例肺良性病变组织中Ｅ-ｃａｄｈｅｒｉｎ蛋白的表达水平。结果　ＮＳＣＬＣ组织中Ｅ-ｃａｄｈｅｒ ｉｎ的阳性表达率为３３.７５％ （２７／８０）,显著低于肺良性病变组织的８０.０％（８／１０）,差异有统计学意义（Ｐ＝０.０１２）。Ｅ-ｃａｄｈｅｒｉｎ表达水平与ＮＳＣＬＣ患者淋巴结转移呈负相关（Ｐ＝０.０３０）,与性别、年龄、吸烟、肿瘤大小、病理类型、分化程度、临床分期均无明显相关性。Ｅ-ｃａｄｈｅｒｉｎ表达与ＮＳＣＬＣ患者的总生存期（ＯＳ）显著相关（Ｐ＝０.０１８）;Ｅ-ｃａｄｈｅｒｉｎ阴性表达者的中位ＯＳ为３１.５个月,阳性表达者为４４.９个月,差异有统计学意义（Ｐ＝０.００３）。结论　Ｅ-ｃａｄｈｅｒｉｎ在ＮＳＣＬＣ淋巴结转移中可能具有重要作用,且与预后密切相关。     

Role of pemetrexed in non-small cell lung cancer

Pemetrexed was approved for the treatment of relapsed or chemotherapy refractory non-small cell lung cancer patients, as it produced similar response and survival outcomes and less toxicity as compared to taxotere. Pemetrexed in combination with platinum analogs or with gemcitabine or vinorelbine, produce equivalent responses and overall survival results compared to combinations of platinum analogs with other drugs. The role of bevacizumab and the inhibitors of epithelial growth factor receptor also should be evaluated in selected patients with NSCLC treated with pemetrexed combinations. Further increases in drug dose may be possible using transfer of drug resistance genes in hematopoietic stem cells.     

顺铂为主的联合化疗治疗晚期非小细胞肺癌120例近期疗效观察

 本文报告了我院1986年1月至1993年10月未用顺铂为主的联合化疗治疗晚期柞小细胞肺癌120例，取得了较好的近期疗效。完全缓解(CR ) 3例(2.5%),部分缓解(PR ) 38例(31.70a),稳定(NS) 49例(40.80a)，进展(PD) 30例(25肠)。有效率(CR+PR)为34.1%。主要毒副l反应为胃肠道反应和骨髓抑制。     

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。     

NP方案治疗晚期非小细胞肺癌疗效观察

目的　观察NVB加PDD治疗晚期非小细胞肺癌疗效。方法　 1999年 7月～ 2 0 0 1年 8月我们应用进口长春瑞滨 (法国皮尔法伯制药公司生产 ) ,NVB 2 5～ 30mg/m2 ,d1,d8,溶于 0 .9%生理盐水15 0ml中快速静滴 ,再以 2 5 0ml0 .9%生理盐水快速静滴 ,DDP 4 0～ 5 0mg/d1,2 ,3,静脉滴注 ,同时给予水化。 2 1天为一周期。结果　本联合化疗方案治疗晚期非小细胞肺癌 4 0例 ,取得了较好疗效 ,其中CR 4例、PR 2 6例 ,总有效率 75 %。结论　NP联合方案治疗晚期肺癌是合理、方便、安全、有效的一种可行的方案 ,可以作为一线方案推荐临床推广。