培美曲塞联合顺铂治疗EGFR-TKI耐药非小细胞肺癌的疗效分析

目的 探讨培美曲塞联合顺铂治疗表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKI)耐药非小细胞肺癌(NSCLC)的疗效.方法 将120例EGFR-TKI耐药NSCLC患者随机分为观察组与对照组,两组样本量均为60例,其中观察组采用培美曲塞联合顺铂治疗,对照组采用多西紫杉醇联合顺铂治疗.结果 两组患者总缓解率(RR)、疾病控制率(DCR)、总生存期(OS)相比差异无统计学意义(P＞0.05),观察组无疾病进展时间(PFS)显著长于对照组,差异有显著性(P＜0.05).观察组中吸烟患者与不吸烟患者的RR、DCR相比差异无统计学意义(P＞0.05),但吸烟患者OS、PFS显著短于不吸烟患者,差异有显著性(P＜0.05).对照组中吸烟患者与不吸烟患者的RR、DCR相比差异无统计学意义(P＞0.05),但吸烟患者OS、PFS显著短于不吸烟患者,差异有显著性(P＜0.05).结论 培美曲塞联合顺铂与多西紫杉醇联合顺铂治疗EGFR-TKI耐药NSCLC的疗效大致相近,且吸烟对上述两个方案的疗效均有一定的影响.     

培美曲塞联合顺铂与多西他赛联合顺铂二线方案治疗晚期肺腺癌的临床对比研究

为了比较培美曲塞联合顺铂与多西他赛联合顺铂二线治疗晚期肺腺癌的临床疗效,将符合入组标准的68例晚期肺腺癌患者随机分为观察组与对照组,每组34例.观察组以培美曲塞联合顺铂化疗,对照组多西他赛联合顺铂化疗.治疗后,CR两组均为0,两组相比差异无统计学意义,P>0.05.疾病控制率(DCR),观察组为23.53%,对照组为20.59%,两组相比差异无统计学意义,P>0.05.毒副反应Ⅱ～Ⅳ级发生率观察组低于对照组,差异有统计学意义,P<0.05.培美曲塞联合顺铂二线治疗肺腺癌临床疗效与多西他赛联合顺铂二线治疗晚期肺腺癌的临床疗效相当,但毒副反应发生率降低.     

培美曲塞联合顺铂治疗晚期非小细胞肺癌的疗效观察

目的观察培美曲塞联合顺铂治疗晚期非小细胞肺癌的疗效及不良反应。方法将我院自2007年1月至2010年5月间收治的晚期非小细胞肺癌患者72例,随机分为观察组和对照组。观察组采用培美曲塞联合顺铂的化疗方案,对照组采用多西他赛联合顺铂的化疗方案。观察2组化疗后的疗效、无进展生存时间、总生存时间以及不良反应等。结果观察组患者CR率8.3%、PR率38.9%、总缓解率47.2%,与对照组患者的CR率(5.6%),PR率(36.1%)以及总缓解率(41.7%)相比,差异均无统计学意义(P>0.05)。2组患者无进展生存时间与总生存时间差异均无统计学意义(P>0.05)。观察组白细胞减少和消化道反应的发生率均显著低于对照组(P<0.05)。结论培美曲塞联合顺铂是晚期非小细胞肺癌有效的治疗方法,不良反应小,患者易于耐受。     

不同二线化疗药物治疗晚期非小细胞肺癌的疗效和安全性比较

目的探讨单用培美曲塞或多西他赛二线化疗药物治疗化疗失败的晚期非小细胞肺癌(NSCLC)的临床疗效及安全性。方法共纳入60例一线治疗失败的局部晚期NSCLC患者,采用随机数字法平均分为A组、B组。A组单用培美曲塞化疗,B组单用多西他赛治疗。观察2组患者的近远期临床疗效及不良反应的发生情况。结果 A组、B组总有效率分别为66.67%、63.33%,2组比较,差异无统计学意义(P>0.05)。A组患者白细胞降低、脱发发生率明显低于B组患者,2组比较差异有统计学意义(P<0.05);血小板降低、贫血、恶性呕吐、皮疹等比较差异不明显(P>0.05)。A组患者6个月、1年生存率分别为46.67%、30.00%,B组6个月、1年生存率分别为40.00%、23.33%,2组比较差异无统计学意义(P>0.05)。结论单用培美曲塞或多西他赛治疗化疗失败的晚期NSCLC均有较好的临床疗效,可作为二线化疗药物,但培美曲塞白细胞降低不良反应较多西他赛发生率低。     

培美曲塞与依托泊苷分别联合顺铂治疗局部晚期非鳞非小细胞肺癌的疗效观察

目的探讨培美曲塞联合顺铂与依托泊苷联合顺铂在胸部同期放化疗中治疗局部晚期非鳞非小细胞肺癌患者的临床疗效比较。方法选取2013年9月至2015年12月间广州市番禺区中心医院收治的60例同期放化疗治疗的局部晚期非鳞非小细胞肺癌患者,采用随机数字表法分为培美曲塞联合顺铂组(AP组)31例和依托泊苷联合顺铂组(EP组)29例。两组患者同时接受胸部同步放化疗,对比两组患者客观有效率、疾病控制率及毒性反应的差异。结果 AP组客观有效率为67.7%,高于EP组的37.9%,差异有统计学意义(P<0.05);两组患者疾病控制率比较,差异无统计学意义(P>0.05)。AP组3/4级毒性反应率为41.9%(13/31),低于EP组的65.5%(19/29),差异有统计学意义(P<0.05);AP组3/4级粒细胞减少发生率为22.6%(7/31),低于EP组的55.2%(16/29),差异有统计学意义(P<0.05)。AP组不良反应发生率为9.7%,低于EP组的44.8%,差异有统计学意义(P<0.05)。结论培美曲塞联合顺铂方案较依托泊苷联合顺铂方案在同期放化疗中治疗晚期非鳞非小细胞肺癌,客观有效率高,疾病控制率相似,毒性反应及不良反应均减少,能否提高生存时间还有待进一步观察。     

吉西他滨联合顺铂化疗对非小细胞肺癌患者肿瘤标志物的影响

目的探讨吉西他滨联合顺铂化疗对非小细胞肺癌患者肿瘤标志物变化的影响。方法选取2014年3月至2014年9月间山东省日照市人民医院收治的90例非小细胞肺癌患者,采用随机数字表法分为GP组(吉西他滨+顺铂)与DP组(多西紫杉醇+顺铂),每组45例,对比两组患者临床疗效、肿瘤标志物变化、卡氏功能状态(Karnofsky)评分、无进展生存期和总生存时间。结果GP组患者治疗总有效率为75.6%,DP组为77.8%,两组比较,差异无统计学意义(P>0.05)。治疗后与治疗前相比,两组患者的肿瘤标志物糖类抗原50(CA50)、细胞角蛋白19片段(CYFRA21-1)和癌胚抗原(CEA)水平均降低,差异均有统计学意义(均P<0.05),而两组患者相比,以上肿瘤标志物水平差异均无统计学意义(均P>0.05)。两组患者的Karnofsky评分、无进展生存期和总生存时间,差异均无统计学意义(均P>0.05)。结论吉西他滨联合顺铂治疗非小细胞肺癌患者疗效突出,能降低肿瘤标志物水平,延长生存时间,提高患者生活质量。     

培美曲塞联合顺铂与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:评估培美曲塞联合顺铂与吉西他滨联合顺铂治疗晚期非小细胞肺癌（NSCLC）的近期疗效及毒副反应。方法:收集有明确病理诊断的晚期NSCLC患者78例,随机分为2组。PP组:选择培美曲塞联合顺铂;GP组:选择吉西他滨联合顺铂化疗。每组各39例,21天为1个周期,2个周期后评价疗效。结果:PP组和GP组总缓解率分别为41.0%和43.6%,无显著性差异（P＞0.05）。PP组血液学毒性的发生率明显低于GP组（P＜0.05）,其他毒副反应比较无统计学差异（P＞0.05）。结论:PP和GP方案均为治疗晚期NSCLC的有效方案,疗效、疾病控制率及中位生存期均相近,但PP方案血液学毒性和脱发较GP方案明显轻,PP方案组患者耐受性更好。     

贝伐单抗联合培美曲塞加顺铂化疗方案对非小细胞肺癌患者生存率的影响

目的 分析贝伐单抗联合培美曲塞加顺铂化疗方案对非小细胞肺癌患者生存率的影响.方法 将我院收治的42例非小细胞肺癌患者随机分为观察组和对照组各21例,观察组患者采用贝伐单抗联合培美曲塞加顺铂化疗方案,对照组患者给予培美曲塞加顺铂化疗方案,21天为1个周期,观察比较两组患者2个周期以上的的近期疗效、远期疗效以及不良反应.结果 观察组客观有效率(ORR)为52.38%,显著高于对照组的28.57%,观察组的疾病控制率(DCR)为71.42%,显著高于对照组的61.9%,两组比较差异有统计学意义;观察组1年、3年和5年的生存率均明显高于对照组,差异有统计学意义;观察组的无进展生存时间(pFS)和总生存时间(OS)均显著优于对照组,两组比较差异有统计学意义;两组的不良反应主要表现在骨髓抑制和胃肠道反应方面,具体表现在血小板减少、贫血、白细胞减少、恶心呕吐、高血压、蛋白尿和鼻出血、咳血等方面,及时给予对症治疗后患者能够继续接受化疗.两组不良反应比较,差异无统计学意义.结论 贝伐单抗联合培美曲塞加顺铂化疗方案对非小细胞肺癌患者的治疗,与培美曲塞加顺铂化疗方案相比,疗效更加显著,患者的生存时间和生存率更高,没有加重患者的不良反应,患者的耐受性比较好,值得临床推广使用.     

多西他赛或培美曲塞联合铂类治疗吉非替尼治疗失败NSCLC的临床比较

目的 探讨多西他赛与培美曲塞分别联合铂类治疗吉非替尼治疗失败NSCLC患者的疗效及不良反应.方法 选取吉非替尼治疗失败NSCLC患者110例,随机数字法分为A组(n=55)和B组(n=55),分别在铂类应用基础上加用多西他赛或培美曲塞辅助治疗.比较两组患者近期疗效、总生存、无进展生存、EORTC QLQ-C30评分和KPS评分改变以及严重不良反应发生率等.结果 两组患者客观缓解率(objective response rate,ORR)和疾病控制率(disease control rate,DCR)比较差异均无统计学意义(均P＞0.05).B组患者无进展生存时间长于A组,差异具有统计学意义(P＜0.05).两组总生存时间比较差异无统计学意义(P＞0.05).两组治疗后EORTC QLQ-C30评分和KPS评分均高于治疗前,且B组治疗后各项评分高于A组(均P＜0.05).B组Ⅲ～Ⅳ级白细胞减少、血红蛋白减少、血小板减少、恶心呕吐、皮疹及肝功能损伤发生率低于A组(均P ＜0.05);两组Ⅲ～Ⅳ级腹泻和脱发发生率比较差异均无统计学意义(均P＞0.05).结论 多西他赛或培美曲塞联合铂类治疗吉非替尼治疗失败NSCLC患者疗效接近,但培美曲塞联合铂类方案可有效延长无进展生存时间,提高生活质量,以及减少严重不良反应发生.     

参芪扶正注射液联合培美曲塞钠+顺铂化疗方案治疗晚期非小细胞肺癌的疗效研究

目的 探讨参芪扶正注射液联合培美曲塞钠+顺铂化疗方案治疗晚期非小细胞肺癌(NSCLC)的临床疗效.方法 将150例晚期NSCLC患者根据用药方案不同分为参芪扶正注射液联合培美曲塞钠+顺铂化疗方案治疗的观察组(72例)和单用培美曲塞钠+顺铂化疗方案治疗的对照组(78例).观察两组患者的近期临床疗效、外周血T淋巴细胞亚群水平、不良反应以及卡氏功能状态(KPS)评分变化.结果 观察组患者的疾病控制率为79.17％,高于对照组的64.10％(P<0.05).治疗后,对照组患者CD3+、CD4+和CD4+/CD8+水平均较治疗前降低(P<0.05),观察组患者CD3+、CD4+和CD4+/CD8+水平均明显高于对照组(P<0.01).观察组患者白细胞减少、血小板减少、肝肾功能不全、胃肠道反应发生率均低于对照组(P<0.05).观察组患者KPS评分有效率为84.72％,高于对照组的67.95％(P<0.05).结论 参芪扶正注射液联合培美曲塞钠+顺铂化疗方案治疗晚期NSCLC能够提高疾病控制率,有效减轻培美曲塞钠+顺铂化疗方案引起的免疫抑制及不良反应,改善患者生活质量.     

Efficacy of third-line pemetrexed monotherapy versus pemetrexed combination with bevacizumab in patients with advanced EGFR mutation-positive lung adenocarcinoma

Objective

The purposes of this study were to observe the effects of different treatment strategies, including third-line pemetrexed alone versus its combination with bevacizumab, in patients with advanced epidermal growth factor receptor (EGFR) mutation-positive lung adenocarcinoma, and to analyze the effects of the different medication orders of first- and second-line drugs on third-line efficacy.

Patients and methods

One hundred and sixteen cases of patients with EGFR-positive lung adenocarcinoma who had received third-line pemetrexed alone or in combination with bevacizumab between March 2010 and March 2014 at Guangzhou Institute of Respiratory Diseases, the First Affiliated Hospital of Guangzhou Medical University were analyzed retrospectively. Additionally, all the patients were treated with first-line gemcitabine and cisplatin (GP) chemotherapy and second-line EGFR tyrosine kinase inhibitor (TKI) or with first-line EGFR-TKI and second-line GP chemotherapy.

Results

The median survival of 61 cases with third-line pemetrexed monotherapy was 36.22 months, the median survival time of 55 cases with third-line pemetrexed plus bevacizumab was 38.76 months, and there was a significant difference in survival time between the two groups (P=0.04). Subgroup analysis revealed that among the 55 cases with third-line bevacizumab plus pemetrexed treatment, the median survival of 29 patients with first-line GP and second-line EGFR-TKI was 42.80 months, while the median survival of 26 patients with first-line EGFR-TKI and second-line GP was only 34.46 months; additionally, there was a significant difference in the survival time between the two subgroups (P=0.001). Among 61 cases with third-line pemetrexed treatment, the median survival of 34 patients with first-line GP and second-line EGFR-TKI was 38.72 months, while the median survival of 27 patients with first-line EGFR-TKI and second-line GP was only 32.94 months; the survival time of the two subgroups was significantly different (P=0.001).

Conclusions

Regardless of the order of the first- and second-line chemotherapy and TKI therapy, the pemetrexed plus bevacizumab regimen was superior to the pemetrexed monotherapy as the third-line therapy in patients with advanced EGFR-positive lung adenocarcinoma. However, this strategy is worth further investigation in prospective studies.     

吉非替尼联合培美曲塞和顺铂治疗晚期非小细胞肺癌的安全性和有效性

目的:比较单用培美曲塞/顺铂化疗或吉非替尼联合培美曲塞/顺铂化疗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,为临床应用提供参考。方法:选择标准一线化疗后复发的晚期NSCLC患者112例,其中联合治疗组52例接受培美曲塞/顺铂及吉非替尼治疗,化疗组60例仅采用培美曲塞和顺铂化疗,评价两组患者的临床疗效及不良反应。结果:联合组客观有效率（objective response rate,ORR）为36.5%,高于化疗组的18.3%（P=0.030）;两组疾病控制率（disease control rate,DCR）分别为71.2%和55.0%（P=0.035）;两组患者的中位无进展生存期（progression free survival,PFS）分别为8.7个月和6.7个月,差别有统计学意义（P=0.047）,但两组患者的中位总生存期（overall survival,OS）差别无统计学意义（P=0.265）。与治疗前相比,两组患者的肿瘤标志物均明显下降,但联合组的CEA和CYFRA21-1水平比化疗组更低（P<0.05）。联合组皮疹和腹泻的发生率高于化疗组（P<0.05）,两组之间其它不良反应的发生率无明显差别（P>0.05）。结论:晚期NSCLC患者一线化疗失败后,采用培美曲塞/顺铂化疗联合吉非替尼靶向治疗较单用化疗显示出更高的ORR和中位PFS,且不良反应可以耐受,值得临床推广运用。     

Clinical Efficacy of Bevacizumab Concomitant with Pemetrexed in Patients with Advanced Non-small Cell Lung Cancer

Objective: To observe the clinical efficacy of bevacizumab concomitant with pemetrexed in patients withadvanced non-small cell lung cancer (NSCLC). Materials and Methods: A total of 72 patients were randomlydivided into a combination group (pemetrexed+bevacizumab, n=36) and a pemetrexed group (n=36) and assessedfor disease control (CR+PR+SD) after 4-cycles of first-line GP chemotherapy (gemcitabine+cisplatin). Clinicalefficacy, progression-free survival time (PFS), overall survival time (OS), overall response rate (ORR), diseasecontrol rate (DCR) and rate of adverse responses between two groups were observed and compared. Results:ORR and DCR were 27.8% and 83.4% in combination group, and 16.7% and 69.5% in the pemetrexed group,respectively, but there were no significant differences (P>0.05). PFS in combination group and pemetrexedgroup were 4.6 months and 3.9 months respectively (P=0.09), whereas OS in the combination group was 14months, evidently higher than in the pemetrexed group (11 months, P=0.004). Adverse responses in both groupsincluded high blood pressure, bleeding, thrombocytopenia, anemia, elevated transaminase, diarrhea, vomitingand proteinuria, but there were no significant differences (P>0.05). Conclusions: Bevacizumab concomitantwith pemetrexed has better clinical efficacy and safety, giving rise to prolonged survival time in patients withadvanced NSCLC.     

培美曲塞联合顺铂与多西他赛联合顺铂治疗晚期非小细胞肺癌的疗效比较

目的比较培美曲塞联合顺铂与多西他赛联合顺铂治疗晚期非小细胞肺癌(NSCLC)的疗效及毒副反应。方法选择我科收治的Ⅲb/Ⅳ期非小细胞肺癌患者60例,采用同期对照研究,随机分为观察组和对照组,每组30例。观察组:培养曲塞500 mg.m-2静滴,d1,顺铂25 mg.m-2静滴,d1～3;对照组:多西地赛75 mg.m-2静滴,d1,8,顺铂25 mg.m-2静滴,d1～3。每3周为1周期重复。每2周期评价疗效,直至疾病进展。结果 60例患者均可评价疗效,观察组总有效率为15.6%,疾病控制率为42.3%,中位生存期为8.9个月,1 a生存率为26.7%;对照组总有效率为13.3%,疾病控制率为40.0%,中位生存期为8.2个月,1 a生存率为23.3%,2组比较差异均无统计学意义(P均>0.05)。观察组骨髓抑制、胃肠道反应、肝功能损害等毒副反应显著低于对照组(P均<0.05)。结论培美曲塞联合顺铂治疗晚期NSCLC的疗效与多西他赛联合顺铂的疗效相近,但毒副反应明显减少,可作为晚期NSCLC患者的一线治疗用药。     

The impact of induction chemotherapy on the outcome of second-line therapy with pemetrexed or docetaxel in patients with advanced non-small-cell lung cancer.

BACKGROUND: Using data from a large phase III study of previously treated advanced non-small-cell lung cancer (NSCLC) that showed similar efficacy for pemetrexed and docetaxel, this retrospective analysis evaluates the impact of first-line chemotherapy on the outcome of second-line chemotherapy. PATIENTS AND METHODS: In all, 571 patients with advanced NSCLC were randomly assigned to receive pemetrexed 500 mg/m(2) or docetaxel 75 mg/m(2) on day 1 of a 21-day cycle. Comparisons were made based on type of first-line therapy [gemcitabine + platinum (GP), taxane + platinum (TP), or other therapies (OT)], response to initial therapy, time since initial therapy, and clinical characteristics. The two second-line treatment groups were pooled for this analysis due to similar efficacy and were assumed to have no interaction with the first-line therapies. RESULTS: Baseline characteristics were generally balanced. By multivariate analysis, gender, stage at diagnosis, performance status (PS), and best response to first-line therapy significantly influenced overall survival (OS). Additional factors by univariate analysis, histology, and time elapsed from first- to second-line therapy significantly influenced OS. CONCLUSIONS: Future trials in the second-line setting should stratify patients by gender, stage at diagnosis, PS, and best response to first-line therapy.     

培美曲塞单药或联合吉非替尼治疗EGFR-TKI耐药后晚期非小细胞肺癌临床观察

背景与目的:生长因子受体-酪氨酸激酶抑制剂(epidermal growth factor receptor-tyrosine kinase inhibitor,EGFR-TKI)治疗晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)获得性耐药后尚无标准的治疗方案,亟待探寻有效的后续治疗方法.为临床应用提供指导,该研究旨在比较后续治疗采用培美曲塞单药或联合吉非替尼治疗EGFR-TKI获得性耐药的晚期NSCLC的临床疗效及安全性.方法:入组既往接受过EGFR-TKI治疗后进展的晚期NSCLC患者62例.其中32接受培美曲塞联合吉非替尼治疗,设为联合组;30例单用培美曲塞治疗,设为化疗组.评价临床疗效及不良反应.结果:联合组客观有效率(objective response rate,ORR)为46.9%,高于化疗组的20%,差异有统计学意义(χ2=4.933,P<0.05);两组疾病控制率(disease control rate,DCR)差异无统计学意义(P>0.05);联合组的中位无病生存期(progression-free survival,PFS)为8.0个月,化疗组中位PFS为6.3个月,差异有统计学意义(χ2=8.063,P<0.05),两组总生存期(overall survival,OS)差异无统计学意义(P>0.05).联合组中性粒细胞减少、皮疹的发生率高于化疗组,差异有统计学意义(P<0.05),Ⅲ~Ⅳ不良反应两组差异无统计学意义(P>0.05).结论:晚期NSCLC患者EGFR-TKI获得性耐药后,采用培美曲塞联合吉非替尼较单用培美曲塞显示出更优势临床有效率和中位PFS,不良反应可耐受,值得临床推广运用.     

安罗替尼联合化疗二线治疗晚期非小细胞肺癌的疗效和安全性

目的:观察安罗替尼联合化疗二线治疗晚期非小细胞肺癌（NSCLC）的疗效与安全性,探索疗效预测指标。方法:2018年11月-2020年5月住院的一线治疗失败的67例Ⅲb/Ⅳ期NSCLC患者,随机分成观察组（34例）和对照组（33例）,两组化疗方案采用多西他赛/培美曲塞单药,观察组联合安罗替尼治疗。观察肿瘤控制率、无进展生存期、总生存期及不良反应,并探索性观察CEA、VEGF及CT碘基值与疗效的相关性。结果:观察组和对照组ORR分别为38.2%和27.2%（P=0.339）,DCR分别为82.4%和57.6%（P=0.027）。两组mPFS分别为6.4个月和4.5个月（P=0.029）,mOS分别为11.2个月和9.2个月（P=0.056）。两组常见不良反应为高血压、乏力、厌食、中性粒细胞减少、手足综合征;不良反应多属1-2级,3级发生率低,未出现药物相关死亡。在CEA、VEGF、CT碘基值方面,观察组治疗前与2周期治疗后均有显著差异（P＜0.05）,对照组治疗前后差异无统计学意义（P＞0.05）,在疗效为CR/PR患者中下降最为显著（P＜0.001）。结论:安罗替尼联合化疗二线治疗晚期NSCLC疗效和生存优于多西他赛/培美曲塞单药,且不良反应可控;CEA、VEGF、CT碘基值有预测疗效价值。     

复治晚期非小细胞肺癌EGFR-TKI治疗失败后培美曲塞与多西他赛挽救性化疗的疗效比较

目的 比较复治晚期非小细胞肺癌（NSCLC）表皮生长因子受体 酪氨酸激酶抑制剂（EGFR TKI）治疗失败后用培美曲塞或多西他赛挽救性化疗的疗效及毒副反应。方法120例复治晚期NSCLC患者于EGFR-TKI治疗失败后分别接受培美曲塞（500mg／m2,d1）或多西他赛（75mg／m2,d1）的挽救性化疗,均21天为1周期。记录并比较两者的疗效和预后。结果培美曲塞组和多西他赛组的有效率（RR）分别为13.4％和5.3％（P=0.307）,疾病控制率（DCR）分别为58.5％和42.1％（P=0.093）,中位无进展生存期（PFS）分别为2.83个月和2.10个月（P=0.862）,中位总生存期（OS）分别为8.40个月和9.10个月（P=0.527）。EGFR-TKI治疗有效和挽救性化疗前行为状态评分（PS）≤1者的中位PFS较长。培美曲塞组1～4级中性粒细胞减少的发生率低于多西他赛组,分别为41.5％和65.8％（P=0.013）。在非血液学毒性方面两组差异均无统计学意义（P＞0.05）。结论 复治晚期NSCLC TKI治疗失败后用培美曲塞或多西他赛挽救性化疗,部分患者仍可以获益,两组疗效相当,且大部分患者能够耐受化疗的毒副反应。对于EGFR-TKI治疗有效、挽救性化疗前PS评分较好的患者,有可能从挽救性化疗中获益更大。     

Meta-analysis of Seven Randomized Control Trials to Assess the Efficacy and Toxicity of Combining EGFR-TKI with Chemotherapy for Patients with Advanced NSCLC who Failed First-Line Treatment

Background: Some recent clinical trials have been conducted to evaluate a combination of EGFR- TKI withchemotherapy for advanced NSCLC patients as second-line therapy, but the results on the efficacy of such trialsare inconsistent. The aim of this meta-analysis was to evaluate the efficacy and safety of combination of EGFR-TKIand chemotherapy for patients with advanced NSCLC who failed first-line treatment. Materials and Methods:We searched relative trials from PubMed, EMBASE, ASCO Abstracts, ESMO Abstracts, Cochrane Libraryand Clinical Trials.gov. Outcomes analyzed were overall response rate (ORR), progression- free survival (PFS),overall survival (OS) and major toxicity. Results: Seven trails eventually were included in this meta-analysis,covering 1,168 patients. The results showed that the combined regimen arm had a significant higher ORR (RR1.76 [1.16, 2.66], p=0.007) and longer PFS (HR 0.75 [0.66-0.85], p<0.00001), but failed to show effects on OS (HR0.88 [0.68- 1.15], p=0.36). In terms of subgroup results, continuation of EGFR-TKI in addition to chemotherapyafter first-line EGFR-TKI resistance confered no improvement in ORR (RR 0.95 [0.68, 1.33], p=0.75) and PFS(HR 0.89[0.69, 1.15], p=0.38), and OS was even shorter (HR1.52 [1.05- 2.21], p=0.03). However, combinationtherapy with EGFR-TKI and chemotherapy after failure of first-line chemotherapy significantly improvedthe ORR (RR 2.06 [1.42, 2.99], p=0.0002), PFS (HR 0.71 [0.61, 0.82], p<0.00001) and OS (HR 0.74 [0.62- 0.88],p=0.0008), clinical benefit being restricted to combining EGFR-TKI with pemetrexed, but not docetaxel. Grade3-4 toxicity was found at significantly higher incidence in the combined regimen arm. Conclusions: Continuationof EGFR-TKI in addition to chemotherapy after first-line EGFR-TKI resistance should be avoided. Combinationtherapy of EGFR-TKI and pemetrexed for advanced NSCLC should be further investigated for prognostic andpredictive factors to find the group with the highest benefit of the combination strategy.     

培美曲塞二钠或多西他赛单药二线治疗晚期非小细胞肺癌的疗效和毒性分析

目的 探讨培美曲塞二钠或多西他赛单药二线治疗晚期非小细胞肺癌的疗效和毒性.方法 选择48例经一线化疗失败的晚期NSCLC患者,按照随机数表法将其分为2组.2组分别实施培美曲塞二钠、多西他赛单药治疗,观察治疗后的不良反应、近期及远期疗效.结果 2组患者化疗后的近期疗效以及远期疗效比较,差异不具有统计学意义(P＞0.05);而培美曲塞二钠组患者化疗后的不良反应远低于多西他赛组,差异具有统计学意义(P＜0.05).结论 培美曲塞二钠在保证对NSCLC的临床治疗效果的同时可以降低其不良反应.