探究培美曲塞与多西他赛在晚期非小细胞肺癌靶向治疗失败后挽救化疗中的临床疗效

目的 研究培美曲塞与多西他赛在晚期非小细胞肺癌靶向治疗失败后挽救化疗中的应用效果。方法 筛选2018 年1 月～2020 年1 月本院的60 例晚期非小细胞肺癌靶向治疗失败后挽救化疗的患者作为研究对象，依据患者选择的药物种类分为观察组和对照组，每组各30 例，对照组采用多西他赛治疗，观察组予以培美曲塞治疗，对比分析两组的近期治疗效果、生存质量评分和毒副反应发生情况。结果 观察组病症控制率为66.67%，对照组病症控制率为36.67%，观察组病症控制效果更好；观察组生存质量评分为（65.2±3.4）分，对照组生存质量评分为（51.7±4.6）分，两组比较差异有统计学意义（t=12.926，P=0.000）；观察组各项毒副反应发生率均低于对照组，差异有统计学意义（P＜0.05）。结论 在晚期非小细胞肺癌靶向治疗失败后进行挽救化疗中选用培美曲塞有更好的治疗效果，可以较好的进行临床治疗，改善患者的生活质量，且产生的毒副反应较少，在实际临床中的应用价值较高。     

吉非替尼联合顺铂治疗晚期非小细胞肺癌的临床研究

目的 回顾性分析吉非替尼联合顺铂治疗晚期非小细胞肺癌的临床疗效。方法 选取2017年2月-2020年4月淮南东方医院集团总医院收治的60例晚期非小细胞肺癌,根据用药方案不同分为对照组和治疗组,每组各30例。对照组化疗第1天静脉滴注注射用培美曲塞二钠,500 mg/m²,注射时间大于10 min,化疗第1~3天静脉滴注顺铂注射液,75 mg/m²,给药前2~16 h和给药后至少6 h内必需进行充分的水化治疗。治疗组从化疗第1天开始口服吉非替尼片,250 mg/d,同时化疗第1~3天静脉滴注顺铂注射液,用法用量同对照组。两组均以3周为1个疗程,治疗2个疗程。观察两组的临床疗效,比较两组治疗前后生活质量相关评分、免疫功能指标、肿瘤标志物、血清细胞因子水平的变化情况。结果 治疗后,治疗组客观缓解率(ORR)、疾病控制率(DCR)分别是60.0%、90.0%,显著高于对照组的33.3%、70.0%(P<0.01)。治疗后,对照组躯体、心理、社会、总分均显著低于治疗前(P<0.05),两组KPS评分显著高于治疗前(P<0.05);治疗后治疗组患者躯体、心理、社会、总分及KPS评分均显著高于对照组(P<0.05)。治疗后,治疗组CD4⁺和CD4⁺/CD8⁺均显著上升,CD8⁺下降(P<0.05);对照组CD4⁺和CD4⁺/CD8⁺均显著下降(P<0.05),CD8⁺有上升趋势但无统计学意义。治疗后,治疗组患者CD4⁺和CD4⁺/CD8⁺显著高于对照组,CD8⁺低于对照组(P<0.05)。治疗后,两组癌胚抗原(CEA)、神经元特异性烯醇化酶(NSE)、血管内皮生长因子(VEGF)均显著下降(P<0.05);且治疗后治疗组CEA、NSE、VEGF水平显著低于对照组(P<0.05)。治疗后,两组患者白细胞介素-2(IL-2)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、干扰素-γ(INF-γ)显著升高,而白细胞介素-4(IL-4)显著降低(P<0.01);且治疗后,治疗组IL-6和INF-γ显著高于对照组(P<0.05)。随访发现,治疗组总生存率(OS)、无进展生存率(PFS)中位生存时间分别为20.6、28个月,对照组为16、19个月。Log-rank (Mantel-Cox) test结果显示,治疗组PFS显著优于对照组(P<0.05),而OS虽有一定趋势但无显著性差异。结论 吉非替尼联合顺铂可有效治疗晚期非小细胞肺癌患者,提高ORR、DCR,改善患者携瘤生活质量,提高无进展生存率,且无显著不良反应。     

清气化痰汤联合化疗对中晚期非小细胞肺癌痰热阻肺证患者CEA、CA125及Cyfra21-1水平的影响

目的:观察清气化痰汤联合化疗对中晚期非小细胞肺癌痰热阻肺证患者血清肿瘤标志物癌胚抗原(CEA)、糖类抗原125(CA125)、细胞角蛋白19片段(CYFRA21-1)的影响。方法:选取2013年1月至2016年12月无锡市中医医院收治的ⅢB、Ⅳ期非小细胞肺癌痰热阻肺证患者40例,随机分为对照组和观察组,每组20例。对照组患者采用化疗,观察组患者在对照组基础上加用清气化痰汤联合治疗。比较2组治疗方案的近期疗效,评价患者的生命质量变化,监测治疗前后血清肿瘤标志物CEA、CA125及Cyfra21-1水平变化,记录不良反应。结果:观察组近期疗效65.0%,高于对照组的30%,差异有统计学意义(P0.05)。观察组经治疗后与生命质量相关的情感、活动功能、生理、社会FACT-L评分较对照组升高显著,差异有统计学意义(P0.05)。观察组患者治疗后的肿瘤标志物CEA、CA125、CYFRA21-1水平均显著低于对照组患者,差异有统计学意义(P0.05)。2组患者均出现恶心呕吐、便秘、血小板降低、白细胞减少等不良反应,观察组发生率均明显降低,与对照组比较差异性显著,差异有统计学意义(P0.05)。结论:清气化痰汤联合化疗能显著提高中晚期非小细胞肺癌痰热阻肺证患者的生命质量,减毒增效优势突出,其机制与下调CEA、CA125、CYFRA21-1等因子表达而诱导癌细胞凋亡有一定相关性,值得临床推广运用。     

重组人血管内皮抑素与薄芝糖肽联合化疗治疗晚期非小细胞肺癌的临床研究

目的：探讨重组人血管内皮抑素与薄芝糖肽联合化疗治疗晚期非小细胞肺癌的近期临床效果和安全性。方法选取2012年1月~2014年4月来本院就诊的102例经病理证实的晚期非小细胞肺癌患者,根据治疗方法,将患者分为两组。对照组48例单纯给予奥沙利铂(L-OHP)+培美曲塞(PEM)化疗方案;实验组54例在对照组基础上给予重组人血管内皮抑素和薄芝糖肽治疗。比较两组患者的临床疗效、生活质量KPS评分、药物毒性反应发生率以及外周血免疫功能变化情况。结果治疗后,实验组患者的近期临床疗效、生活质量KPS评分优于对照组(P<0.05)。两组患者治疗后的CD4+、CD8+均较治疗前降低,对照组降低更明显,两组治疗后的CD4+、CD8+差异有统计学意义(P<0.05)。结论重组人血管内皮抑素与薄芝糖肽联合化疗治疗晚期非小细胞肺癌具有较好的近期效果,能提高患者在化疗过程中的生活质量,改善其免疫功能。     

The Safety and Efficacy of Single‐Agent Pemetrexed in Platinum‐Resistant Advanced Urothelial Carcinoma: A Large Single‐Institution Experience

Background.

Pemetrexed is a commonly used treatment for platinum-resistant advanced urothelial carcinoma (UC) based on objective response rates of 8% and 28% in two small phase II studies. To address the discrepancy in reported response rates and to assess efficacy and toxicity outside of a clinical trial setting, we performed a large retrospective analysis of pemetrexed use at Memorial Sloan Kettering Cancer Center. We also investigated candidate prognostic factors for overall survival in this setting to explore whether the neutrophil-lymphocyte ratio (NLR) had independent prognostic significance.

Patients and Methods.

Patients receiving pemetrexed for platinum-resistant advanced UC between 2008 and 2013 were identified. The Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) were used to determine response rate. Kaplan-Meier and Cox regression analyses were used to examine the association of various factors with efficacy and survival outcomes. Hematologic toxicity and laboratory abnormalities were recorded.

Results.

One hundred and twenty-nine patients were treated with pemetrexed. The objective response rate was 5% (95% confidence interval: 1%–9%), and the median duration of response was 8 months. Median progression-free survival (PFS) was 2.4 months, and the 6-month PFS rate was 14%. There was no significant difference in response rate by age, Eastern Cooperative Oncology Group (ECOG) performance status, or number of prior therapies. On multivariable analysis, ECOG performance status (p < .01), liver metastases (p = .02), and NLR (p < .01) had independent prognostic significance for overall survival.

Conclusion.

This 129-patient series is the largest reported data set describing pemetrexed use in advanced UC. Activity was modest, although discovery of molecular biomarkers predictive of response would be valuable to identify the small subset of patients who do gain significant benefit. Overall, the data highlight the urgent need to develop novel therapies for these patients.     

Retrospective efficacy and safety analyses of erlotinib,pemetrexed, and docetaxel in EGFR-mutation-negative patients with previously treated advanced non-squamous non-small-cell lung cancer

ObjectiveSeveral guidelines recommend erlotinib, pemetrexed, or docetaxel for second-line chemotherapy in patients with advanced non-squamous non-small-cell lung cancer (NSCLC). The aim of this study was to retrospectively evaluate the efficacy of erlotinib, pemetrexed, and docetaxel in epidermal growth factor receptor (EGFR) mutation-negative patients with previously treated advanced non-squamous NSCLC.Materials and methodsWe analyzed the efficacy of these agents in patients with previously treated advanced non-squamous NSCLC who had EGFR wild-type tumors, performance status (PS) of 0, 1, or 2 and received erlotinib, pemetrexed, or docetaxel between December 2007 and September 2011. Variability among patient backgrounds was evaluated using propensity scores to assess comparability. The efficacy of these agents was evaluated in patient subgroups with low variability.ResultsThe propensity scores showed that the backgrounds of the groups that received second-line therapy with each agent had low variability and were adequate for comparison. Patients were divided into the PS0/1 and PS2 groups for analysis. The median progression-free survival (PFS) in patients treated with erlotinib was 2.8 months in the PS0/1 group, as compared with 1.0 month in the PS0/1/2 group and 0.90 months in the PS2 group. PFS in PS0/1 patients who received erlotinib was comparable to that in PS0/1 patients who received pemetrexed (2.5 months) or docetaxel (1.9 months). Overall survival (OS) in erlotinib-, pemetrexed-, and docetaxel-treated PS0/1 patients was 16.1, 7.4 and 10.0 months, respectively. The study had limited power to detect differences in PFS and OS because of the small sample size.ConclusionsErlotinib appears to be a useful second-line option in PS0/1 patients with EGFR mutation-negative advanced non-squamous NSCLC given its mild adverse effects. The results should be carefully interpreted because of the small sample size, limited power, and retrospective nature of the study.     

培美曲塞联合顺铂对吸烟与不吸烟晚期肺腺癌患者的临床疗效观察

目的观察吸烟对肺腺癌患者培美曲塞联合顺铂治疗疗效的影响。方法分析2010年2月-2012年2月徐州医学院附属医院肿瘤科收治的83例经病理学或细胞学确诊的初治ⅢB、Ⅳ期肺腺癌患者。吸烟组33例,不吸烟组50例,初治采用培美曲塞联合顺铂方案（培美曲塞500 mg·m^-2第1天静脉滴注,顺铂30 mg·m^-2第1-3天静脉滴注）化疗,21天为1个周期,每治疗两个周期后评价疗效,直至病情进展。近期疗效评价指标为疾病控制率（DCR）,远期疗效评价指标为疾病进展时间（TTP）和1年生存率,毒副反应评价指标为骨髓抑制毒性、消化道反应等。结果吸烟组与不吸烟组DCR分别为60.6%和76.0%;TTP分别为（5.7±1.6）月和（6.7±1.8）月,1年生存率分别为24.24%和46.0%。两组DCR比较（χ2=2.238,P=0.135）,差异无统计学意义,TTP（t=2.55,P=0.013）及1年生存率（χ2=4.022,P=0.045）的差异有统计学意义。吸烟组与不吸烟组骨髓抑制毒性、消化道反应、口腔炎/咽炎、感染发生率的差异均无统计学意义（P〉0.05）。结论不吸烟晚期肺腺癌患者一线应用培美曲塞治疗较吸烟患者可有更明显的远期获益。     

Phase I Trial of Cediranib in Combination with Cisplatin and Pemetrexed in Chemonaive Patients with Unresectable Malignant Pleural Mesothelioma (SWOG S0905)

IntroductionIn malignant pleural mesothelioma, targeting angiogenesis with cediranib, a vascular endothelial growth factor receptor and platelet-derived growth factor receptor inhibitor, may have therapeutic potential.MethodsS0905 phase I combined cediranib (two dose cohorts [30 mg and 20 mg daily]) with cisplatin-pemetrexed for six cycles followed by maintenance cediranib in unresectable chemonaive patients with malignant pleural mesothelioma of any histologic subtype. The primary end point established the maximum tolerated dose in combination with cisplatin-pemetrexed in a dose deescalation scheme.ResultsA total of 20 patients were enrolled (seven to the 30-mg cohort and 13 to the 20-mag cohort). In the cediranib 30-mg cohort, two of the initial six patients reported dose-limiting toxicities and the dose was deemed too toxic to continue. In the next cohort, two patients experienced dose-limiting toxicities, and thus, the maximum tolerated dose of cediranib was established as 20 mg. During the six cycles of cisplatin-pemetrexed-cediranib, 20 mg, there were grade 3 toxicities (neutropenia and gastrointestinal) and grade 4 thrombocytopenia. No patients had any significant episodes of bleeding. According to the Response Evaluation Criteria in Solid Tumors (n = 17 evaluable patients), the median progression-free survival was 12.8 months (95% confidence interval [CI]: 6.9–17.2); according to the Modified Response Evaluation Criteria in Solid Tumors (n = 19 evaluable patients), the median progression-free survival was 8.6 months (95% CI: 6.1–10.9). For all patients, the disease control rate at 6 weeks was 90% and median overall survival time was 16.2 months (95% CI: 10.5–28.7).ConclusionsCediranib combined with cisplatin-pemetrexed has a reasonable toxicity profile and preliminary promising efficacy. The phase II S0905 trial will evaluate the efficacy of the triplet regimen compared with the current standard of care, cisplatin-pemetrexed.     

吉非替尼联合培美曲塞治疗吉非替尼二线治疗进展后肺腺癌的疗效观察

目的观察吉非替尼联合培美曲塞治疗吉非替尼二线治疗进展后肺腺癌的疗效及安全性。方法选取2010年10月至2012年12月间74例一线化疗进展后给予吉非替尼治疗有效再次进展患者,随机分为观察组和对照组两组。观察组患者36例,采用培美曲塞500mg/m2,静脉滴注;吉非替尼250mg/d,口服,21d为1个周期;对照组患者38例,单用培美曲塞500mg/m2,静脉滴注,21d为1个周期。所有患者至少治疗2个周期。结果观察组近期治疗效果优于对照组,但两组差异无统计学意义;与对照组相比,观察组死亡率略低,中位进展时间和中位生存时间均更长,两组在死亡率、生存时间和进展时间方面比较,差异无统计学意义（P〉0.05）;两组不良反应差异无统计学意义（P〉0.05）。结论采用吉非替尼二线治疗进展后联合培美曲塞治疗非小细胞癌肺腺癌,其治疗效果明显,不良反应能耐受,有利于提高肺腺癌患者的生活质量,有望成为非小细胞肺癌（NSCLC）患者标准的三线治疗方案。