Erlotinib-based targeted dual agent versus erlotinib alone in previously treated advanced non-small-cell lung cancer: a meta-analysis of 13 randomized controlled trials

Objectives: To compare the effects of an erlotinib-based targeted dual agent with erlotinib alone in previously treated patients with advanced non-small lung cancer (NSCLC).

Patients and methods: The PubMed and Embase databases and the Cochrane Central Register of Controlled Trials were searched for publications between January 2005 and March 2016. Hazard ratios (HRs) with their 95% confidence intervals (CIs), or data for calculating HRs with 95% CIs were derived. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and toxicity were assessed.

Results: Thirteen trials with a total of 4509 patients were included in this meta-analysis. Compared with erlotinib alone, combination therapy showed no improvement in OS (HR?=?0.95; 95% CI, 0.89–1.02; P?=?.132) though significantly prolonged PFS (HR?=?0.82; 95% CI, 0.75–0.90; P?<?.001). Combination therapy significantly increased ORR (RR?=?1.32; 95% CI, 1.09–1.60; P?=?.005) and DCR (RR?=?1.26; 95% CI, 1.17–1.36, P?<?.001). Sub-analysis assessment failed to identify any sub-groups which could benefit from combination therapy in terms of OS. Combination therapy was associated with more grade 3 or higher toxic effects (RR?=?1.54; 95% CI, 1.22–1.95; P?<?.001). Patients treated with combination therapy had more grade 3 or greater fatigue (RR?=?1.49; 95% CI, 1.16–1.91; P?=?.002), but did not develop more diarrhea (RR?=?2.02; 95% CI, 0.86–4.77; P?=?.107) or rash (RR?=?1.29, 95% CI, 0.90–1.85; P?=?.172). This study had limitations about heterogeneities among the included trials, and the analysis was not based on individual patient data.

Conclusions: Compared with erlotinib alone, the erlotinib-based targeted dual agent showed a minimal magnitude of improvement in PFS but did not improve OS. The role of erlotinib-based combinations in previously treated patients with NSCLC seemed insignificant.     

培美曲塞在晚期非小细胞肺癌姑息性化疗中的作用探析

目的 探讨培美曲塞在晚期非小细胞肺癌姑息性化疗中的效果.方法 66例晚期非小细胞肺癌患者,采用随机数字表法分为对照组和观察组,每组33例.两组患者均采用顺铂进行姑息性化疗治疗,在此基础上,对照组增加吉西他滨进行化疗,观察组增加培美曲塞进行化疗.比较两组患者短期疗效、化疗不良反应发生情况及治疗前后免疫功能指标.结果 观察...     

Angiogenesis inhibitors for patients with ovarian cancer: a meta-analysis of 12 randomized controlled trials

Objectives:

To investigate the effects of angiogenesis inhibitors in the treatment of patients with advanced or recurrent ovarian cancer, a meta-analysis was performed and overall survival (OS), progression-free survival (PFS), and toxicity were assessed.

Patients and methods:

The PubMed and Embase databases, and the Cochrane Central Register of Controlled Trials were searched for publications between January 2000 and June 2015. Hazard ratios (HRs) with their 95% confidence intervals (CIs), or data for calculating HRs with 95% CIs were derived.

Results:

The 12 trials in this meta-analysis were divided into three groups: four trials with a VEGF inhibitor (the bevacizumab group), six trials with VEGFR inhibitors (the VEGFRIs group), and two trials with an angiopoietin inhibitor (the trebananib group). PFS improvement was seen in all groups (HR?=?0.61, 95% CI 0.48 to 0.79, P?<?0.001 for bevacizumab; HR?=?0.71, 95% CI 0.59 to 0.87, P?=?0.001 for VEGFRIs; and HR?=?0.67, 95% CI 0.62 to 0.72, P?<?0.001 for trebananib). Regarding OS, bevacizumab showed a trend of improvement (HR?=?0.90, 95% CI 0.80 to 1.01, P?=?0.079), VEGFRIs showed no improvement (HR?=?0.92, 95% CI 0.75 to 1.11, P?=?0.368), and trebananib demonstrated a significant prolongation (HR?=?0.81, 95% CI 0.67 to 0.99, P?=?0.036). Bevacizumab was associated with more class-specific adverse events (RR?=?4.05, 95% CI 1.99 to 8.27, P?<?0.001). Although the toxicity profiles differed, VEGFRIs developed common higher incidences of hypertension, diarrhea, and fatigue. A higher incidence of edema was reported in the trebananib group (RR?=?2.60, 95% CI 0.84 to 8.00, P?=?0.097).

Conclusions:

Anti-angiogenic therapy showed clear PFS benefit with increased toxicity, but its role in OS was undefined for ovarian cancer which emphasized the need for patient selection.     

Further data on beta-blockers and cancer risk: observational study and meta-analysis of randomized clinical trials

Abstract

Background:

The aim of the present paper is to provide some further data on the relationship between β-blocker treatment and the incidence of cancer, using two different approaches (epidemiological study and meta-analysis of clinical trials).     

培美曲塞治疗晚期胃肠道恶性肿瘤的临床疗效评价

目的 探讨培美曲塞治疗晚期胃肠道恶性肿瘤的临床疗效与安全性.方法 回顾性分析本院2010年1月至2012年11月人院的1 14例晚期胃肠道恶性肿瘤患者按是否给予培美曲塞治疗分为两组.单药化疗组均采用铂类、5-FU或紫杉类化疗药治疗,联合化疗组均在以上基础上加用培美曲塞治疗,比较两组患者各类型恶性肿瘤治疗效果、生存期与不良反应等.结果 联合化疗组治疗总有效率(RR)与疾病控制率(DCR)显著性高于单药化疗组,两组比较差异有统计学意义(P＜0.01);联合化疗组2年生存率明显高于单药化疗组(76.19％ vs.56.86％),差异有统计学意义(P＜0.05);3年生存率显著高于单药化疗组(49.21％ vs.23.53％),差异有统计学意义(P＜0.01);联合化疗组患者相关不良反应发生率明显高于单药化疗组(47.92％vs.69.84％),差异有统计学意义(P＜0.05).结论 培美曲塞治疗晚期胃肠道恶性肿瘤的临床疗效显著,但存在一定不良反应,应给予对症处理.     

Statin therapy on pulmonary function in patients with COPD: a meta-analysis of randomized controlled trials

In thecurrent meta-analysis, we aimed to investigate the therapeutic effects of statins on pulmonary function inpatients with chronic obstructive pulmonary disease (COPD).MEDLINE, EMBASE and Cochrane Central Register of clinical trials were systematically searched until January 2017 for RCTs of statins. Only trials with COPD patients were included.The I² statistic was used to measure heterogeneity between trials and calculated mean differences for pulmonary function parameters with fixed-effect meta-analysis.Eighteligible studies with 534 participants were identified. Statin therapy had no remarkable influence on FEV1 (SMD –0.01, 95% CI –0.204 to 0.184, I²=0.0%, P = 0.922, n = 409), FEV1/ FVC (SMD 0.163, 95% CI –0.044to 0.369, I²=0.0%, P = 0.123, n = 364), 6MWD, heart rate or CRP. However, exercise time on treadmill was remarkably improved by statin therapy (SMD 1.271, 95% CI 0.930 to 1.612, I²=0.0%, P = 0.000, n = 160). Subgroup analysis showed significant, ameliorative effect of pravastatin on FEV1/FVC (SMD 0.362, 95% CI 0.049 to 0.674, I²=0.0%, P = 0.023).The results of this meta-analysis showed non-significant effect of statins on pulmonary function in COPD patients. Based on the studies reviewed, it is not recommended to prescribe statins for COPD patients without CVD risk factors due to lack of clearly defined benefit.     

Incidence and risk of denosumab-related hypocalcemia in cancer patients: a systematic review and pooled analysis of randomized controlled studies

Abstract

Purpose:

The aim of this study is to evaluate the frequency and relative risk of hypocalcemia in cancer patients receiving denosumab.     

Risk of high-grade bleeding in patients with cancer treated with bevacizumab: a meta-analysis of randomized controlled trials

Purpose  

High-grade bleeding is a serious adverse event associated with bevacizumab, a humanized monoclonal antibody targeting vascular endothelial growth factor and widely used in the current cancer treatments. The aim of this study was to gain a better understanding of the overall incidence and risk of high-grade bleeding in cancer patients who receive bevacizumab therapy.     

培美曲塞与DP方案在非小细胞肺癌二线治疗中临床疗效观察

目的 比较DP 方案与培美曲塞在晚期非小细胞肺癌(NSCLC) 治疗中的近期疗效和毒副反应.方法 NSCLC 患者27例.分别接受DP方案和培美曲塞两种方案的治疗,其中培美曲塞组13例,DP组14例,治疗2个周期后分别评价疗效和毒副反应.结果 有效率培美曲塞组为23.1%,DP组为28.6%,差异无统计学意义(P>0....     

Meta-analysis of randomized controlled trials for the incidence and risk of fatal adverse events in cancer patients treated with ipilimumab

Background: Ipilimumab is a fully human immunoglobulin G1 monoclonal antibody that increases antitumor T-cell responses. We conducted a meta-analysis of randomized controlled trials (RCTs) to evaluate the risk of FAEs associated with ipilimumab.

Methods: We searched PubMed, EMBASE, and ASCO meeting abstract up to September 2016 for RCT comparing ipilimumab with no ipilimumab on cancer patients. Incidence rates, relative risk ratios (RRs), and 95% confidence intervals (CIs) were calculated using fixed- or random effects models. The primary end point was the association of ipilimumab with FAEs. Subgroup analyses were performed according to tumor type, concurrent therapy, and dose of ipilimumab.

Results: A total of 5,466 patients from 10 RCTs were included. For patients receiving ipilimumab, the overall incidences of FAEs was 0.99% (95% CI: 0.48%-1.69%). Allocation to ipilimumab therapy increased the risk of FAEs (RR = 2.16, 95% CI, 1.03–4.54) significantly. Subgroup analyses reached statistical significance for prostate cancer, high dose of ipilimumab, and placebo as a control group. No evidence of publication bias was observed.

Conclusions: Compared with control or placebo, ipilimumab was associated with an increased risk of FAEs in cancer patients. As ipilimumab gains greater clinical use, practitioners must be aware of the risks associated with its use.     

培美曲塞治疗晚期复发非小细胞肺癌临床观察

目的评价培美曲塞治疗晚期化疗后进展的非小细胞肺癌的疗效和毒副反应。方法46例经病理确诊既往化疗失败的晚期非小细胞肺癌患者,培美曲塞500mg／m^2静脉滴注,第1天,每21d为1个周期,并口服地塞米松、叶酸和肌内注射维生素B12以减轻毒副反应。根据RECIST标准对客观缓解率进行评价,毒副反应评价按美国NCI制定的毒性评价标准。结果46例可评价,总RR为10．6％。疾病控制率为45．7％,中位无进展生存期为3个月,中位生存期为7个月。毒副反应主要是中性粒细胞下降。结论培美曲塞治疗既往化疗失败的晚期非小细胞肺癌,具有较好的疗效和安全性。     

培美曲塞和多西他赛分别与顺铂联用治疗非小细胞肺癌的效果观察

目的观察培美曲塞和多西他赛分别联合N$13治疗非小细胞肺癌（NSCLC）的临床疗效及不良反应发生情况。方法共纳入NSCLC患者54例。培美曲塞组28例,接受培美曲塞500-600mg／m^2＋顺铂75mg／m^2治疗,第1天。多西他赛组26例,给予多西他赛70—80mg／m^2＋顺铂75mg／m^2治疗,第1天。2组均应用地塞米松预防过敏。3周为1个化疗周期,化疗3个周期。观察化疗期间疗效及药物不良反应。结果培美曲塞组患者部分缓解10例（35．7％）,稳定14例（50．0％）,进展4例（14．3％）,客观缓解率为35．7％,疾病控制率为85．7％。多西他赛组部分缓解9例（34．6％）,稳定13例（50．0％）,进展4例（15．4％）,客观缓解率为34．6％,疾病控制率为84．6％。2组药物客观缓解率和疾病控制率差异无统计学意义（均P〉0．05）。多西他赛组血液毒性和脱发发生率明显高于培美曲塞组[分别为65．4％（17／26）比50．0％（14／28）,23．1％（6／26）比0．0;均P〈0．05]。结论培美曲塞联合顺铂与多西他赛联合顺铂治疗NSCLC近期疗效相似,但培美曲塞不良反应更小。     

Efficacy of gemcitabine-based chemotherapy in metastatic breast cancer: a meta-analysis of randomized controlled trials

Abstract

Objectives:

To compare the effects of gemcitabine-based chemotherapy and gemcitabine-free regimens, a meta-analysis of all relevant randomized controlled trials was performed to investigate the improvement in overall response rate (ORR), time to progression (TTP), and overall survival (OS). A subgroup of gemcitabine-based doublet compared with single agent was also analyzed.     

培美曲塞和多西他赛在老年晚期非鳞非小细胞肺癌二线治疗中的疗效及安全性比较

目的比较培美曲塞和多西他赛在老年晚期非鳞非小细胞肺癌（NSCLC）二线治疗中的疗效和安全性。方法收集2009年1月至2012年3月首都医科大学宣武医院胸外科收治的年龄≥65岁晚期非鳞NSCLC患者的病历资料进行回顾性分析。按照化疗方案将患者分为培美曲塞组 （500 mg/m2静脉滴注,第1天）和多西他赛组（75 mg/m2静脉滴注,第1天）。每个治疗周期均约3～4周。比较2组患者治疗2个周期后的客观有效率、疾病控制率和不良反应发生率。结果纳入分析的患者共146例。培美曲塞组56例,男性30例,女性26例,年龄65～83岁,平均（69.6±4.7）岁;多西他赛组90例,男性62例,女性28例,年龄65～83岁,平均（67.9±4.5）岁。2组患者肺癌病理类型、分期和体力状况评分差异均无统计学意义。治疗2个周期后培美曲塞组客观有效率明显高于多西他赛组［32.1%（18/56）比17.8%（16/90）,P=0.046］,疾病控制率培美曲塞组与多西他赛组差异无统计学意义［73.2%（41/56）比77.8%（16/90）,P=0.530］。2组均有患者出现粒细胞减少、血小板减少、贫血、恶心呕吐、周围神经毒性、脱发等不良反应,培美曲塞组Ⅲ～Ⅳ级粒细胞减少、脱发和Ⅰ～Ⅱ级周围神经毒性发生率均明显低于多西他赛组 ［7.1%（4/56）比27.8%（25/90）,P=0001;21.4%（12/56）比52.2%（47/90）, P=0000;17.9%（10/56）比33.3%（30/90）, P=004）］。 2组均无发生肾功能损害者及因化疗不良反应而死亡者。结论培美曲塞和多西他赛用于老年晚期非鳞NSCLC二线治疗均有效,但培美曲塞较多西他赛更安全。     

培美曲塞二钠联合卡铂治疗老年中晚期非小细胞肺癌的临床探讨

目的 探讨培美曲塞二钠联合卡铂治疗老年中晚期非小细胞肺癌的临床效果.方法 采集我院2012年9月至2014年12月收治的100例中晚期非小细胞肺癌患者,将所有患者随机分为观察组和对照组,每组50例.观察组患者采用培美曲塞二钠联合卡铂治疗,对照组患者采用吉西他滨联合卡铂治疗.结果 观察组患者的总有效率为56％,对照组患者的总有效率为50％,两组比较差异无统计学意义(P＞0.05).观察组患者治疗后血液学毒性不良反应共9例,消化道毒性不良反应共5例,生化毒性不良反应共3例,其他不良反应共4例,均明显少于对照组(P＜0.05).观察组患者的肿瘤进展时间(TTP)为(6.9±1.1)个月,中位生存时间(MST)为(8.6±1.3)个月,1年生存率为52.6％,与对照组比较均有统计学差异(P＜0.05).结论 培美曲塞二钠联合卡铂治疗老年中晚期非小细胞肺癌不良反应少,生存时间长.     

Erlotinib and pemetrexed as maintenance therapy for advanced non-small-cell lung cancer: a systematic review and indirect comparison

Abstract

Background:

Two new agents have recently been licensed as maintenance therapy for advanced non-small-cell lung cancer (NSCLC) by the US Food and Drug Administration. This paper aims to systematically review the evidence from all available clinical trials of erlotinib and pemetrexed as maintenance therapy for advanced NSCLC.     

Paclitaxel-based versus docetaxel-based regimens in metastatic breast cancer: a systematic review and meta-analysis of randomized controlled trials

Abstract

Objectives:

Docetaxel and paclitaxel show significant clinical activity in metastatic breast cancer (MBC) and have been approved for MBC by the U.S. Food and Drug Administration, but it is still unclear whether a paclitaxel-based regimen improves outcomes over a docetaxel-based regimen in patients with MBC. We therefore performed a meta-analysis of randomized controlled trials to compare the safety and efficacy of these two regimens in MBC.