cN-II expression predicts survival in patients receiving gemcitabine for advanced non-small cell lung cancer

Resistance to gemcitabine is likely to be multifactorial and could involve a number of mechanisms involved in drug penetration, metabolism and targeting. In vitro studies of resistant human cell lines have confirmed that human equilibrative nucleoside transporter 1 (hENT1)-deficient cells display resistance to gemcitabine. Overexpression of certain nucleotidases, such as cN-II, has also been frequently shown in gemcitabine-resistant models. In this study, we applied immunohistochemical methods to assess the protein abundance of cN-II, hENT1, human concentrative nucleoside transporter 3 (hCNT3) and deoxycitidine kinase (dCK) in malignant cells in from 43 patients with treatment-na?ve locally advanced or metastatic non-small cell lung cancer (NSCLC). All patients subsequently received gemcitabine-based chemotherapy. Response to chemotherapy, progression-free survival (PFS), and overall survival (OS) were correlated with abundance of these proteins. Among the 43 samples, only 7 (16%) expressed detectable hENT1, with a low percentage of positive cells, 18 expressed hCNT3 (42%), 36 (86%) expressed cN-II and 28 (66%) expressed dCK. In univariate analysis, only cN-II expression levels were correlated with overall survival. None of the parameters were correlated with freedom from progression survival nor with response. Patients with low levels of expression of cN-II (less than 40% positively stained cells) had worse overall survival than patients with higher levels of cN-II expression (6 months and 11 months, respectively). In a multivariate analysis taking into account age, sex, weight loss, stage and immunohistochemical results, cN-II was the only predictive factor associated with overall survival. This study suggests that cN-II nucleotidase expression levels identify subgroups of NSCLC patients with different outcomes under gemcitabine-based therapy. Larger prospective studies are warranted to confirm the predictive value of cN-II in these patients.     

Correlation of CDA, ERCC1, and XPD polymorphisms with response and survival in gemcitabine/cisplatin-treated advanced non-small cell lung cancer patients.

PURPOSE: Selecting patients according to key genetic characteristics may help to tailor chemotherapy and optimize the treatment in non-small cell lung cancer (NSCLC). Polymorphisms at the xeroderma pigmentosum group D (XPD), excision repair cross-complementing 1 (ERCC1), and cytidine deaminase (CDA) genes have been associated with alterations in enzymatic activity and may change sensitivity to the widely used cisplatin-gemcitabine regimen. EXPERIMENTAL DESIGN: Analyses of CDA, XPD, and ERCC1 polymorphisms were done on blood samples of 65 chemotherapy-na?ve, advanced NSCLC patients treated with cisplatin-gemcitabine. Furthermore, CDA enzymatic activity was evaluated by high-performance liquid chromatography analysis. Association between XPD Asp(312)Asn and Lys(751)Gln, ERCC1 C118T, and CDA Lys(27)Gln polymorphisms and response, clinical benefit, toxicity, time to progression (TTP), and overall survival (OS) was estimated using Pearson's chi(2) tests, the Kaplan-Meier method, the log-rank test, and the Cox proportional hazards model. RESULTS: The CDA Lys(27)Lys polymorphism significantly correlated with better clinical benefit (P = 0.04) and grade > or =3 neutropenia and thrombocytopenia, as well as with longer TTP and OS (P = 0.006 and P = 0.002, respectively), whereas no significant associations were found among ERCC1 and XPD polymorphisms and both response and clinical outcome. Finally, the enzymatic activity assay showed a significant lower mean in subjects harboring the CDA Lys(27)Lys polymorphism. CONCLUSIONS: Our data suggested the role of CDA Lys(27)Lys polymorphism as a possible predictive marker of activity, toxicity, TTP, and OS in advanced NSCLC patients treated with cisplatin and gemcitabine. These results may be explained by the lower enzymatic activity associated with the Lys(27)Lys CDA and offer a potential new tool for treatment optimization.     

GP方案治疗RRM1蛋白低表达的晚期非小细胞肺癌的疗效观察(英文)

Objective:The aim of this study was to observe the efficacy of gemcitabine combined with cisplatin(GP)in advanced non-small cell lung cancer(NSCLC)patients with low expression of ribonucleotide reductase 1(RRM1)protein using immunohistochemistry.Methods:RRM1 protein expression in tumor tissue was detected by streptavidin-peroxidase (SP)method of immunohistochemistry.GP regimen(gemcitabine 1000-1250 mg d1,d8,cisplatin 75 mg/m2)was given to advanced NSCLC patients with low expression of RRM1 protein.Results:I...     

吉西他滨联合奥沙利铂治疗晚期非小细胞肺癌64例临床分析

目的观察吉西他滨联合奥沙利铂方案治疗晚期非小细胞肺癌疗效和毒副反应。方法64例确诊的Ⅲb-Ⅳ期患者接受了此方案的治疗。年龄35-78岁,中位年龄61岁。吉西他滨1 000 m g/m^2＋生理盐水250 m l,静滴30分钟,d1、d8;奥沙利铂130 mg/m^2,3小时静滴,d2;21天后行第二周期。观察近期疗效和1、2年生存率。同时评价其血液、消化道和神经等毒性反应。结果全组有效率为39.1%,疾病稳定为28.1%。32.8%的患者出现疾病进展,中位生存期为10个月,肿瘤进展时间为5个月。1年生存率为35.9%,2年生存率为14.1%。鳞癌的有效率为45.0%,其中有2例复治的病例达完全缓解;腺癌的有效率为31.2%,无完全缓解病例。初治者有效率为43.5%,复治者有效率为27.8%。年龄≥65周岁的有效率为41.2%,〈65周岁的有效率为38.2%。男性有效率为39.5%,女性有效率为38.1%。全组有12.5%和14.1%的患者分别出现Ⅲ-Ⅳ度白细胞和血小板下降,6.7%出现Ⅲ度贫血。消化系统毒性主要为轻微的恶心、呕吐,4.7%出现Ⅲ度腹泻。20.3%出现Ⅲ度神经毒性。无治疗相关死亡。结论吉西他滨联合奥沙利铂方案治疗晚期非小细胞肺癌疗效较好,毒副反应能耐受。     

健择联合顺铂治疗晚期非小细胞肺癌疗效观察

目的:评价健择(GEM)联合顺铂(DDP)治疗晚期非小细胞肺癌(NSCLC)的疗效和毒副反应。方法:收集NSCLC患者38例给予GP方案化疗,GEM1000mg/m2iv d1,8;DDP80mg/m2iv d1,28天为一周期,应用2周期后评价疗效。结果:全组有效率46.9%,无CR病例,鳞癌和腺癌有效率分别为44.0%和46.1%,初治、复治有效率分别为46.9%、33.3%,Ⅲ、Ⅳ期有效率为47.6%、41.2%。毒副反应主要为白细胞下降68.4%,其次为消化道症状为42.1%。结论:GP方案治疗NSCLC疗效较好,毒副反应轻。     

吉西他滨联合奥沙利铂治疗晚期非小细胞肺癌临床观察

背景与目的奥沙利铂在肺癌治疗中应用较少,本观察的目的为了解奥沙利铂联合吉西他滨治疗晚期非小细胞肺癌的疗效及毒副反应。方法对32例晚期非小细胞肺癌患者给予奥沙利铂65mg/m^2第1、8天静脉输注;吉西他滨800-1000mg/m^2,第1、8天静脉输注。21天为一个周期,完成2周期治疗后评价疗效。结果全组患者可评价疗效31例,无完全缓解,部分缓解7例,稳定15例,进展9例,总有效率22.6%,疾病控制率71.0%。中位疾病无进展生存7个月,中位生存期14.5个月。1年生存率59.0%,2年生存率45.8%。主要毒性反应为骨髓抑制和恶心呕吐。结论奥沙利铂联合吉西他滨治疗晚期非小细胞肺癌有一定疗效,可延长生存期,毒副反应可耐受,生存质量下降不明显。     

吉西他滨联合顺铂治疗晚期非小细胞肺癌的临床研究

目的评价吉西他滨(gemcitabine)联合顺铂治疗晚期非小细胞肺癌的疗效及毒副反应。方法选择经病理证实的晚期非小细胞肺癌41例住院患者采用GP方案行静脉化疗，具体为Gemcitabine 1250mg/m^2d1、d8，DDP30mg/m^2d1-d3，21天重复，至少使用2周期以上。结果完全缓解(CR)4．9％(2／41)，部分缓解(PR)43．9％(18／41)，稳定(SD)34．1％(14／41)，进展(PD)17．00k，(7／41)，总有效率(RR)48．80%；肿瘤控制率(CR PR SD)为82．19％；中位缓解期7．1m，中位生存期11m(4．5～20m)；毒副反应以白细胞及血小板下降、消化道反应、乏力为常见，均可耐受，无化疗相关死亡。结论吉西他滨联合顺铂对晚期非小细胞肺癌有较好疗效，毒副反应可以耐受，值得临床推广。     

健择联合顺铂治疗晚期非小细胞肺癌的临床研究

目的　观察健择 (gemcitabine)联合顺铂治疗晚期非小细胞肺癌的疗效及毒性反应。方法　经病理细胞学证实的 46例晚期非小细胞肺癌患者采用健择 +顺铂方案 :健择 10 0 0mg/m2 ,第 1,8天 ;顺铂 80mg/m2 ,第 1天或分 3d应用 ,2 1d为 1个周期。结果　完全缓解 (CR) 1例 ,部分缓解 (PR) 2 0例 ,稳定 (SD) 19例 ,进展 (PD) 6例 ,总有效率 45.7%。初治 2 4例中 ,CR +PR 14例 ,有效率58.3 % ;复治 2 2例中 ,CR +PR 7例 ,有效率 3 1.8% ,两组差异有显著性 (P <0 .0 5)。毒副反应以白细胞及血小板下降为常见 ,但均可耐受。结论　健择联合顺铂对晚期非小细胞肺癌有较好疗效 ,毒副反应可以耐受     

吉西他滨联合奥沙利铂或顺铂治疗老年人晚期非小细胞肺癌的随机对照临床研究

背景与目的化疗可延长患者生存期，改善生活质量，是治疗晚期非小细胞肺癌的主要方法。对于70岁及以上的老年晚期非小细胞肺癌患者，治疗的毒副反应和治疗耐受性尤其重要。本研究的目的是观察比较吉西他滨联合奥沙利铂和吉西他滨联合顺铂治疗70岁及以上老年人晚期非小细胞肺癌的疗效和毒副反应。方法42例患者按随机表法分为GO组20例（吉西他滨1000mg／m^2，第1、8天；奥沙利铂65mg／m^2，第1、8天）和GP组22例（吉西他滨1000mg／m^2，第1、8天；顺铂30mg／m^2，第1～3天），28天为一周期，均治疗2周期以上。结果GO组CR1例，PR10例，SD7例，PD2例，有效率为55．0％；中位生存期为11．2月，1年生存率为45％。GP组PR9例，SD10例，PD3例，有效率为40．9％；中位生存期为11．8月，1年生存率为50％。两组有效率、中位生存期和1年生存率比较均无显著性差异（P均〉0．05）。毒副反应以白细胞降低和胃肠道反应为主，GP组Ⅲ＋Ⅳ度白细胞下降发生率和恶心呕吐发生率均显著高于GO组（17．4％VS4．8％，20．7％VS3．6％，P均〈0．05），GP组Ⅰ＋Ⅱ度脱发和肾功能异常发生率均显著高于GO组（43．5％ vs 10．7％，14．1％ vs 2．4％，P均〈0．05）。结论对于70岁及以上老年人晚期非小细胞肺癌，吉西他滨加奥沙利铂方案有较好的近期疗效，毒副反应轻，治疗耐受性好，临床应用更安全。     

Nedaplatin/gemcitabine versus carboplatin/gemcitabine in treatment of advanced non-small cell lung cancer: A randomized clinical trial

Objective: To evaluate the efficacy and safety of nedaplatin/gemcitabine (NG) and carboplatin/gemcitabine (CG) in the management of untreated advanced non‐small cell lung cancer (NSCLC). Methods: Sixty‐two patients with previously untreated advanced NSCLC were recruited between June 2006 and November 2007. Subjects were randomly assigned to the NG arm (n=30) and the CG arm (n=32). Only patients (24 and 25 in the NG and CG arms, respectively) who completed ≥2 chemotherapy cycles were included in the data analysis. The primary outcome measure was the objective response rate (ORR). The secondary outcome measures included progression‐free survival (PFS), overall survival (OS) and adverse events. Results: There were no statistically significant differences in the efficacy measures (ORR, P=0.305; median PFS, P=0.198; median OS, P=0.961) or in the major adverse events (grade 3/4 neutropenia, P=0.666; grade 3/4 anemia, P=0.263; grade 3/4 thrombocytopenia, P=0.212) between the two treatment arms. However, there was a trend towards higher ORR (37.5% vs. 24.0%), longer PFS (6.0 vs. 5.0 months), and less adverse events in the NG arm. Conclusion: NG regimen seems to be superior over CG regimen for advance NSCLS, but further investigation is needed to validate this superiority.     

吉西他滨联合培美曲塞治疗晚期非小细胞肺癌

目的观察吉西他滨联合培美曲塞方案治疗晚期非小细胞肺癌（NSCLC）的疗效及毒性。方法经组织学证实的NSCLC患者13例,给予吉西他滨联合培美曲塞方案化疗：吉西他滨（gem c itab ine）1 000 mg/m2,静脉注射,d1、d8;培美曲塞（pem etrexed）500 mg/m2,静脉注射,d1。培美曲塞用药前预防性应用维生素B12、叶酸及地塞米松。21-28天为1个周期。2周期后进行疗效评价。结果完全缓解（CR）0例,部分缓解（PR）2例,稳定（SD）5例,进展（PD）6例,有效率（RR）为15.4%,临床获益率（CBR）为53.8%。中位疾病进展时间（TTP）为4.4（2-6）月。主要毒性反应为骨髓抑制,表现为可逆性的白细胞减少及血小板减少。结论吉西他滨联合培美曲塞方案治疗晚期非小细胞肺癌是一种疗效可靠,毒性可以耐受的方案。     

吉西他滨联合顺铂治疗老年晚期非小细胞肺癌临床观察

为了评价吉西他滨联合顺铂进行适当剂量调整后,在治疗老年晚期非小细胞肺癌患者中的疗效和毒副反应,对病理确诊的112例晚期老年NSCLC患者采用GP方案化疗.吉西他滨800 mg/m2,d1,d8,静脉滴入;顺铂25 mg/m2,d1～d3,静脉滴入.21 d为1个周期,至少化疗2个周期后评价疗效.4例完全缓解(CR),33例部分缓解(PR),24例稳定(SD),51例进展(PD),总有效率为33.0%.其中腺癌有效率为31.0%,鳞癌有效率为37.0%,腺癌、鳞癌两组之间比较差异无统计学意义,P>0.05.初治有效率为40.0%,复治有效率为19.4%,两组疗效比较差异有统计学意义,P<0.05.吉西他滨联合顺铂方案治疗老年非小细胞肺癌疗效较好,且毒副反应轻,对于老年、体能状态评分(PS)不佳的晚期复发进展NSCLC患者值得推荐.     

Elderly patients with advanced non-small cell lung cancer. A pase II study with weekly cisplatin and gemcitabine

OBJECTIVES: The incidence of non-small cell lung cancer (NSCLC) is increasing among the elderly. We studied the toxicity and efficacy of a weekly schedule of gemcitabine and cisplatin in elderly patients with advanced NSCLC. METHODS: Patients aged 70 years or above with advanced NSCLC were treated in a phase II prospective trial with gemcitabine 1,000 mg/m(2) and cisplatin 35 mg/m(2) on days 1, 8 and 15 every 28 days. RESULTS: Forty-eight patients with a median age of 74 years (range 70-78) participated in the study. We observed 14 cases with partial response, 14 with stable disease and 16 with progressive disease, whilst 4 patients were not evaluable. By intention-to-treat analysis, partial response rate was 31.8% whilst progressive disease was 33.3%. Median survival was 9 months; 1-year survival probability was 34.4% and median time to progression was 4 months. Grade III-IV leukopenia was observed in 5/48 patients (10.4%), 20/48 patients (41.7%) had grade III-IV thrombocytopenia and 7/48 patients (14.6%) had grade III-IV anemia. One patient experienced grade III emesis and 2 patients had grade III-IV fatigue. CONCLUSIONS: At this dose and schedule the combination of gemcitabine and cisplatin appears to be an active and well-tolerated regimen for elderly patients with advanced NSCLC.     

吉西他滨调整方案治疗晚期非小细胞肺癌的Ⅱ期临床试验

背景与目的吉西他滨与铂类的联合化疗是晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)最常用的治疗方案。通常3周方案中的吉西他滨需间隔1周给药。为提高依从性,本研究将吉西他滨第8天给药时间调整为第5天,并评价调整方案一线治疗晚期NSCLC的疗效及安全性。方法 2007年10月-2009年10月共入组83例晚期NSCLC患者,采用吉西他滨1,000mg/m2-1,250mg/m2第1天、第5天静脉滴注30min,联合顺铂75mg/m2,或联合卡铂(AUC=5)第1天静滴,每21天为1周期,每例至少完成2周期治疗后评价疗效,观察毒性反应及无进展生存期和总生存期。结果 83例患者的客观有效率为37.3%,中位无进展生存期和中位生存期分别为6.1个月和15.0个月,1年、2年生存率分别为57.8%与16.2%。调整方案的主要不良反应为血液学毒性与胃肠道反应,III度-IV度白细胞、血红蛋白、血小板减少发生率分别为26.5%、10.8%、7.2%,联合顺铂治疗组III度-IV度胃肠道反应发生率为27.5%。无治疗相关死亡。结论吉西他滨联合铂类5天调整方案一线治疗晚期NSCLC疗效肯定,毒副反应可耐受,值得进一步开展随机对照研究。     

国产吉西他滨联合顺铂治疗28例晚期非小细胞肺癌

目的：评价国产吉西他滨（gemcitabine,GEM）联合顺铂方案治疗晚期非小细胞肺癌的疗效和不良反应。方法：对经病理组织学或细胞学证实的28例晚期非小细胞肺癌患者采用GP方案化疗：GEM1000mg/m^2ivdrip第1、8日,DDP30mg/m^2ivdrip第1-3日,21日为1周期。结果：CR0例,PR12例,SD14例,PD2例,总有效率为42.8%,初治、复治各14例,均有6例PR,有效率均为42.8%,不良反应以消化道反应及白细胞、血小板下降为主,均可耐受。结论：国产吉西他滨联合顺铂对晚期非小细胞肺癌有较好疗效,毒副反应可以耐受,可作为一线或二线化疗方案。