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Efficacy and safety of apatinib alone or apatinib plus paclitaxel/docetaxel versus paclitaxel/docetaxel in the treatment of advanced non-small cell lung cancer: A meta-analysis.
Li, Z, Liu, Z, Wu, Y, Li, H, Sun, Z, Han, C, Zhang, X, Zhang, J
Thoracic cancer. 2021;(21):2838-2848
Abstract
BACKGROUND To investigate the efficacy and safety of apatinib alone or apatinib plus paclitaxel/docetaxel versus paclitaxel/docetaxel in the treatment of advanced non-small cell lung cancer (NSCLC) through pooling of open published data. METHODS The electronic databases of Medline (1960-2021.5), Cochrane central register of controlled trials (CENTRAL), EMBASE(1980-2021.5) and Wan fang (1986-2021.5) were systematically searched by two reviewers to identify the relevant clinical trials related to the above subject. The objective response rate (ORR), disease control rate (DCR) and drug relevant adverse reactions were pooled and demonstrated by risk ratio (RR) and 95% confidence interval (95% CI). The statistical heterogeneity across studies was assessed by I-square test. The publication bias was evaluated by Egger's line regression test and demonstrated by Begg's funnel plot. RESULTS Eleven prospective studies were included in the meta-analysis. The pooled results indicated that the ORR (RR = 1.62, 95% CI: 1.32-2.00, p < 0.05) and DCR (RR = 1.29, 95% CI: 1.18-1.41, p < 0.05) of apatinib alone or apatinib plus paclitaxel/docetaxel was significantly higher than that of the paclitaxel/docetaxel group for advanced NSCLC, respectively. The drug-related adverse reaction was not statistically different between apatinib alone or apatinib plus paclitaxel/docetaxel with regard to the hand-foot syndrome, gastrointestinal reaction, thrombocytopenia, anemia and leukocytopenia (pall > 0.05) except for hypertension (RR = 3.60, 95% CI: 1.26-10.31, p < 0.05). Subgroup analysis also indicated that the hypertension and hand-foot syndrome in apatinib + paclitaxel/docetaxel were higher than that of the paclitaxel/docetaxel group with a statistical difference (p < 0.05). CONCLUSIONS Apatinib alone or apatinib plus paclitaxel/docetaxel was superior to paclitaxel/docetaxel for ORR and DCR. However, combined treatment with apatinib appears to increase the risk of a patient developing an adverse reaction, especially hypertension and hand-foot syndrome.
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Clinical efficacy and safety of Aidi injection plus paclitaxel-based chemotherapy for advanced non-small cell lung cancer: A meta-analysis of 31 randomized controlled trials following the PRISMA guidelines.
Xiao, Z, Wang, C, Zhou, M, Hu, S, Jiang, Y, Huang, X, Li, N, Feng, J, Tang, F, Chen, X, et al
Journal of ethnopharmacology. 2019;:110-122
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE As an important Chinese herb injection, Aidi injection is composed of the extracts from Astragalus, Eleutherococcus senticosus, Ginseng, and Cantharis. Aidi injection plus paclitaxel-based chemotherapy is often used to in the treatment of non-small cell lung cancer (NSCLC) in China. AIM OF THE STUDY The objective of this study is to further confirm whether Aidi injection can improve the tumor responses and survivals, and reveal its safety, optimal usage and combination with paclitaxel. MATERIALS AND METHODS A meta-analysis was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. All randomized controlled trials (RCTs) concerning the Aidi injection plus paclitaxel-based chemotherapy for NSCLC were selected. Main outcomes were objective response rate (ORR), disease control rate (DCR), survivals, quality of life (QOL) and adverse drug reactions (ADRs). All data were extracted by using a standard data extraction form and synthesized through meta-analysis. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used for rating the quality of evidence. RESULTS Thirty-one RCTs involving 2058 patients were included, and most trials had an unclear methodological bias risk. The risk ratio (RR) and 95% confidence intervals (CI) of ORR, DCR, QOL, neutropenia, thrombocytopenia, gastrointestinal toxicity and liver injury were as following: 1.32 (1.20-1.46), 1.14 (1.09-1.20), 1.89 (1.66-2.16), 0.61 (0.51-0.74), 0.62 (0.45-0.87), 0.59 (0.49-0.72) and 0.52 (0.36-0.75). Compared to chemotherapy alone, all differences were statistically significant. Subgroup analysis showed that only with the TP, Aidi injection could increase the ORR and DCR. Treatment with 100 ml, 80 ml or 50 ml/time, and 14 days/2 cycles or 21 days/2-4 cycles, Aidi injection could increase the ORR and DCR, respectively. Sensitivity analysis showed that the results had good robustness. None of the trials reported the overall survivals (OS), progression free survival (PFS). The quality of evidences was moderate. CONCLUSIONS Current moderate evidence revealed that Aidi injection plus paclitaxel-based chemotherapy, especially TP can significantly improve the clinical efficacy and QOL for patients with stage III/IV NSCLC. Aidi injection can relieve the risk of hematotoxicity, gastrointestinal toxicity and liver injury in patient with NSCLC receiving paclitaxel-based chemotherapy. The optimal usage may be 50 ml/time and 14 days/2 cycles.
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Evidence of Astragalus injection combined platinum-based chemotherapy in advanced nonsmall cell lung cancer patients: A systematic review and meta-analysis.
Cao, A, He, H, Wang, Q, Li, L, An, Y, Zhou, X
Medicine. 2019;(11):e14798
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Abstract
BACKGROUND Platinum-based chemotherapy is one of the standard treatments for advanced nonsmall cell lung cancer (NSCLC). Despite on an effective treatment for advanced NSCLC patients, its high toxicity and limited clinical effects have raised big concerns. Astragalus injection (AGI) has been commonly employed as an adjutant chemotherapy drug for NSCLC in China. This review was conducted to evaluate the beneficial of AGI in combination with platinum-based chemotherapy in advanced NSCLC. METHODS We collected all studies about AGI plus platinum-based chemotherapy for advanced NSCLC in the PubMed, EMBASE, China National Knowledge Infrastructure Database, the Cochrane Library, Wanfang Database, China Biological Medicine Database, and Chinese Scientific Journal Database established on July 2018 without language restriction. Cochrane handbook was applied to assess the quality of included trials. Stata (version 12.0) and RevMan (version 5.3) were employed for data analysis. The quality of the evidence was assessed with the GRADE approach. RESULTS Nineteen randomized controlled trials (RCTs) including 1635 patients were included to determine the effectiveness and safety of AGI combined with platinum-based chemotherapy in the treatment of NSCLC. The result of meta-analysis indicated that comparing with chemotherapy alone, AGI combined chemotherapy could significantly improve the objective response rate (relative risk [RR] = 1.19, 95% confidence interval [CI] [1.06, 1.33], P = .002), the Karnofsky performance status (RR = 2.28, 95% CI [1.63, 3.18], P < .00001), and 1-year survival rate (RR = 1.40, 95% CI [1.16, 1.70], P = .0005), meanwhile increase the percentages of CD3 (weighted mean differences [WMD] = 11.98, 95% CI [8.0, 15.96], P < .00001), CD4 (WMD = 2.98, 95% CI [0.45, 5.52], P = .02), CD4/CD8 (WMD = 0.33, 95% CI [0.20, 0.46], P < .00001), and NK cells (WMD = 9.5, 95% CI [7.25, 11.76], P < .00001), decrease the incidence of leukopenia (RR = 0.52, 95% CI [0.44, 0.61], P < .00001), platelet toxicity (RR = 0.62, 95% CI [0.50, 0.76], P < .00001), and vomiting (RR = 0.72, 95% CI [0.60, 0.87], P = .0006). Based on the system evaluation results, the GRADE system recommendation grading method was adopted to evaluate the evidence quality. The results showed that the level of evidence was low. CONCLUSIONS The AGI apparently has attenuation and synergistic efficacy to platinum-based chemotherapy patients. However, considering the limits of articles included in the present researches, the recommendation is likely to be weak. High-quality RCTs are urgently used to generate conclusive results.
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Pretreatment prognostic nutritional index as a prognostic factor in lung cancer: Review and meta-analysis.
Wang, Z, Wang, Y, Zhang, X, Zhang, T
Clinica chimica acta; international journal of clinical chemistry. 2018;:303-310
Abstract
BACKGROUND Numerous studies have explored the association between pretreatment prognostic nutritional index (PNI) and prognosis in lung cancer (LC), but the results are still inconclusive. We systematically evaluated the prognostic value of pretreatment PNI in LC patients by conducting a meta-analysis. METHODS A comprehensive literature search was performed by retrieving PubMed, EMBASE, and Web of Science, Wan Fang and CNKI databases. We used hazard ratios (HRs) and their 95% confidence intervals (CIs) to assess the associations of PNI with overall survival (OS), disease-free survival/recurrence-free survival (DFS/RFS) and progression-free survival (PFS) in LC patients. RESULTS A total of 21 studies were enrolled into this meta-analysis, with 17 about no-small cell lung cancer (NSCLC) and 4 about on small-cell lung cancer (SCLC). The results indicated that NSCLC patients with low PNI had shorter OS (HR: 1.59, 95% CI: 1.28-1.96, P = 0.001), DFS/RFS (HR = 1.74, 95% CI = 1.08-2.80, P = 0.017), and PFS (HR = 1.52, 95% CI = 1.26-1.83, P = 0.002) than patients with high PNI. The robustness of these pooled results were verified by our stratified analysis and sensitivity analysis. Besides, a pooled analysis of 4 studies about SCLC suggested that low PNI was closely associated with worse OS in SCLC patients as well. CONCLUSION Low PNI predicts poor survival in LC patients.
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Prognostic value of pretreatment prognostic nutritional index in non-small cell lung cancer: A systematic review and meta-analysis.
Hu, Y, Shen, J, Liu, R, Feng, Z, Zhang, C, Ling, L, Chen, L
The International journal of biological markers. 2018;(4):372-378
Abstract
BACKGROUND The pretreatment prognostic nutritional index has been considered a potential prognostic biomarker in patients with non-small cell lung cancer (NSCLC), but this remains controversial. Therefore, we performed a meta-analysis to systematically assess the prognostic value of the prognostic nutritional index in patients with NSCLC. METHODS We systematically searched PubMed, EMBASE, Web of Science, and CNKI. The hazard ratios (HRs) with their corresponding 95% confidence intervals (CIs) were used to evaluate the link between the prognostic nutritional index and the oncological outcomes of patients with NSCLC, including overall survival, disease-free survival/recurrence-free survival, and progression-free survival. RESULTS Fifteen studies were included in this meta-analysis. Twelve of these studies explored the association between the prognostic nutritional index and the overall survival of patients with NSCLC. Our pooled analysis indicated that a low prognostic nutritional index was significantly related to adverse overall survival (HR 1.61; 95% CI 1.44, 1.81; P < 0.001). Our results also showed that the prognostic nutritional index was a negative predictor for disease-free survival/recurrence-free survival, and progression-free survival in patients with NSCLC. CONCLUSION Our meta-analysis demonstrated that there was a close association between the prognostic nutritional index value and prognosis in NSCLC patients and that the prognostic nutritional index may act as a useful prognostic biomarker in NSCLC patients.
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Association between Retinoic acid receptor-β hypermethylation and NSCLC risk: a meta-analysis and literature review.
Li, Y, Lu, DG, Ma, YM, Liu, H
Oncotarget. 2017;(4):5814-5822
Abstract
Emerging evidence indicates that Retinoic acid receptor-β (RARβ) is a tumor suppressor in many types of tumor. However, whether or not RARβ is a risk factor and is correlated to clinicopathological characteristics of non-small cell lung cancer (NSCLC) remains unclear. In this report, we performed a meta-analysis to determine the effects of RARβ hypermethylation on the incidence of NSCLC and clinicopathological characteristics in human NSCLC patients. Final valuation and analysis of 1780 cancer patients from 16 eligible studies was performed. RARβ hypermethylation was found to be significantly higher in NSCLC than in normal lung tissue, the pooled OR from 7 studies including 646 NSCLC and 580 normal lung tissues, OR = 6.05, 95% CI = 3.56-10.25, p<0.00001. RARβ hypermethylation was significantly higher in adenocarcinoma (AC) compared to squamous cell carcinoma (SCC), pooled OR is 0.68 (95% CI = 0.52-0.89, p = 0.005). RARβ hypermethylation was also found to occur significantly higher in smoker (n = 232) than non-smoker (n = 213) (OR = 2.46, 95% CI = 1.54-3.93, p = 0.0002). Our results indicate that RARβ hypermethylation correlates well with an increased risk in NSCLC patients. RARβ geneinactivation caused by RARβ methylation contributes the NSCLC tumorigenesis and may serve as a potential risk factor, diagnostic marker and drug target of NSCLC.
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Evaluation of efficacy and safety of different pembrolizumab dose/schedules in treatment of non-small-cell lung cancer and melanoma: a systematic review.
Abdel-Rahman, O
Immunotherapy. 2016;(12):1383-1391
Abstract
AIM: Pembrolizumab is a fully humanized anti-PD-1 agent currently approved for the treatment of advanced melanoma and pretreated non-small-cell lung cancer (NSCLC). OBJECTIVE To assess the efficacy and safety of different dose schedules of pembrolizumab in the treatment of patients with advanced NSCLC and melanoma. Search method: MEDLINE database has been searched. Reference lists of original studies and review articles were checked for other related articles. SELECTION CRITERIA Prospective clinical trials reporting the outcomes of more than one dose schedule of pembrolizumab in the treatment of advanced NSCLC and melanoma. DATA COLLECTION & ANALYSIS The review author extracted information on the outcomes of the study for this review, and presented the results. MAIN RESULTS Four trials with 3425 patients were included in this systematic review. Pooled analysis for the odds ratio of objective response rate comparing 2 versus 10 mg/kg every 3 weeks in advanced melanoma was 1.03 (95% CI: 0.71-1.49; p = 0.89), while for advanced NSCLC, it was 0.97 (95% CI: 0.66-1.43; p = 0.87). Moreover, odds ratio for selected side effects between the two doses was as follows: rash: 0.83 (95 CI: 0.58-1.18; p = 0.29); vitiligo: 1.27 (95% CI: 0.62-2.61; p = 0.52); diarrhea: 0.94 (95% CI: 0.63-1.42; p = 0.79); hypothyroidism: 0.97 (95% CI: 0.63-1.50; p = 0.90); hepatitis/elevated transaminases: 1.86 (95% CI: 0.91-3.79; p = 0.09); nephritis: 0.88 (95% CI: 0.32-2.44; p = 0.80); pneumonitis: 1.17 (95% CI: 0.62-2.23; p = 0.63). CONCLUSIONS Given the equivalence in efficacy and safety between lower doses and higher doses of pembrolizumab, 2 mg/kg every 3 weeks seems to be an appropriate dose for routine practice in advanced pretreated NSCLC and melanoma.
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BRAF mutations in patients with non-small cell lung cancer: a systematic review and meta-analysis.
Chen, D, Zhang, LQ, Huang, JF, Liu, K, Chuai, ZR, Yang, Z, Wang, YX, Shi, DC, Liu, Q, Huang, Q, et al
PloS one. 2014;(6):e101354
Abstract
BACKGROUND BRAF mutations have been well described in non-small cell lung cancer (NSCLC) for several years, but the clinical features of patients harboring BRAF mutations are still not well described. We performed a meta-analysis to identify common clinical features in NSCLC patients carrying BRAF mutations. METHODS We identified clinical studies that examined the association between BRAF mutations and features of NSCLC within PubMed, Embase and ISI Science Citation Index database up to October 2013. The effect size of clinical features was estimated by odds ratios (ORs) with 95% confidence interval (CI) for each study, using a fixed-effects or random-effects model. RESULTS Ten studies with a total of 5599 NSCLC patients were included. There was a 3% (170/5599) BRAF mutation rate. BRAF mutations in NSCLC were significantly associated with adenocarcinomas (ADCs) (compared with non-ADCs, OR = 4.96, 95%CI = 2.29-10.75). There were no significant differences in gender, smoking and stage in patients with and without BRAF mutations. The BRAFV600E mutation was more frequent in women than non-BRAFV600E mutations (OR = 0.27, 95%CI = 0.12-0.59), and was closely related to never smokers (OR = 0.14, 95%CI = 0.05-0.42). CONCLUSIONS These findings have important implications for the prediction of the NSCLC sub-types more accurately combined with other genetic changes.
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Methylenetetrahydrofolate reductase gene C677T polymorphism and lung cancer: an updated meta-analysis.
Hou, XH, Huang, YM, Mi, YY
Asian Pacific journal of cancer prevention : APJCP. 2012;(5):2025-9
Abstract
OBJECTIVE Methylenetetrahydrofolate reductase (MTHFR) catalyzes the metabolism of folate and nucleotides needed for DNA synthesis and repair. Variations in MTHFR functions likely play roles in the etiology of lung cancer (LC). So far, several studies between MTHFR C677T polymorphism and LC provide controversial or inconclusive results. METHODS To better assess the purported relationship, we performed a meta-analysis of 14 publications. Eligible studies were identified by searching the Pubmed, Embase, Web of Science and Google Scholar databases. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association. RESULTS Overall, no significant association was detected between the MTHFR C677T polymorphism and LC risk, the same as in race subgroup. However, in the stratified analysis by histological type, significantly increased non-small-cell lung cancer (NSCLC) risk was indicated (T-allele vs. C-allele: OR=1.11, 95%CI=1.03-1.19; TT vs. CC: OR=1.24, 95%CI=1.09-1.41; TC vs. CC: OR=1.11, 95%CI=1.03-1.20 and TT+TC vs. CC: OR=1.09, 95%CI=1.03-1.15). At the same time, ever-smokers who carried T-allele (TT+TC) had a 10% decreased LC risk compared with CC genotype carriers. CONCLUSIONS Our study provided evidence that the MTHFR 677T null genotype may increase NSCLC risk, however, it may protect ever-smokers against LC risk. Future studies with large sample sizes are warranted to further evaluate this association in more detail.
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A literature-based meta-analysis of clinical risk factors for development of radiation induced pneumonitis.
Vogelius, IR, Bentzen, SM
Acta oncologica (Stockholm, Sweden). 2012;(8):975-83
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INTRODUCTION The risk of developing side effects after radiotherapy is not only dependent on radiation dose, but may also be affected by patient-related risk factors. Here we perform a literature-based meta-analysis to estimate the effect of various clinical risk factors on the incidence of symptomatic radiation pneumonitis (RP). MATERIAL AND METHODS A systematic review of English language articles in the Pubmed, Embase and Cochrane controlled trials registers. Studies with the mesh term "radiation pneumonitis" or the search term "radiation pneumonitis" were included. Additional studies were identified by manual searching of the references. Studies reporting crude incidence or odds ratios (OR) for radiation pneumonitis vs. age, disease location, smoking status, chemotherapy schedule or comorbidity were included. A systematic overview (meta-analysis) was conducted to synthesize data across multiple studies. RESULTS Significant risk factors for RP were: older age (OR = 1.7, p < 0.0001); disease located in mid-lower lung (OR = 1.9, p = 0.002); presence of comorbidity (OR = 2.3, p = 0.007). Ongoing smoking was found to protect against RP (OR = 0.6, p = 0.008). History of smoking tended to protect against RP (OR = 0.7, p = 0.06). Sequential (rather than concomitant) chemotherapy scheduling (OR = 1.6, p = 0.01) increased RP risk, but treatment intensity and patients selection are likely confounders. CONCLUSION This systematic overview revealed several clinical risk factors for RP that have not been unambiguously identified in the literature. These risk factors should be considered when defining dose-volume constraints for radiation treatment plan optimization.