Safety and efficacy of addition of VEGFR and EGFR-family oral small-molecule tyrosine kinase inhibitors to cytotoxic chemotherapy in solid cancers: A systematic review and meta-analysis of randomized controlled trials

2014 ◽  
Vol 40 (5) ◽  
pp. 636-647 ◽  
Author(s):  
Tomohiro Funakoshi ◽  
Asma Latif ◽  
Matthew D. Galsky
Keyword(s):  
Systematic Review ◽  
Randomized Controlled Trials ◽  
Small Molecule ◽  
Kinase Inhibitors ◽  
Meta Analysis ◽  
Cytotoxic Chemotherapy ◽  
Controlled Trials ◽  
Safety And Efficacy ◽  
Randomized Controlled ◽  
Egfr Family

Safety and efficacy of addition of VEGFR and EGFR-family small-molecule tyrosine kinase inhibitors to cytotoxic chemotherapy in solid cancers: A meta-analysis.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 415-415
Author(s):  
Tomohiro Funakoshi ◽  
Asma Latif ◽  
Matt D. Galsky
Keyword(s):  
Adverse Events ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Small Molecule ◽  
Randomized Trials ◽  
Kinase Inhibitors ◽  
Meta Analysis ◽  
Cytotoxic Chemotherapy ◽  
Safety And Efficacy ◽  
Egfr Family

415 Background: The approach of combining cytotoxic chemotherapy with small molecule tyrosine kinase inhibitors (TKIs) has been explored in a large number of randomized trials, in a diverse range of tumor. We performed a systematic review and meta-analysis to evaluate the safety and efficacy of this therapeutic approach. Methods: PubMed and the ASCO databases were searched up to March 2013. Eligible studies included randomized trials in which the FDA approved TKI in combination with chemotherapy was compared with chemotherapy alone in patients with any type of solid cancer. The endpoints included safety [fatal adverse events (FAEs), treatment discontinuation, any severe (grade 3 or 4) adverse events (AEs), and individual severe AEs] and efficacy [progression-free survival (PFS), and overall survival (OS)]. The pooled relative risk (RR) or hazard ratio (HR), with corresponding 95% confidence intervals (CI) were calculated. Results: A total of 16,011 patients from 43 trials were included. Among the 43 trials, ten met their primary efficacy endpoints. Among the 21 phase III trials, two led to Food and Drug Administration approval for the combination. Compared with chemotherapy alone, the addition of a TKI significantly increased the risk of FAEs (RR, 1.63; 95% CI, 1.32-2.01), treatment discontinuation (RR, 1.80; 95% CI, 1.58-2.06), and any severe AE (RR, 1.25; 95% CI, 1.16-1.36). Compared with chemotherapy alone, the addition of a TKI was associated with a significant improvement in PFS (HR, 0.82; 95% CI, 0.76-0.89), but not OS (HR, 0.99; 95% CI, 0.95-1.03). Chemotherapy plus TKI was also associated with a significant higher risk of seven of the 11 evaluated individual AEs: neutropenia (RR, 1.18; P =.004), thrombocytopenia (RR, 1.70; P <.001), febrile neutropenia (RR, 1.48; P <.001), hypertension (RR, 3.01; P <.001), skin toxicities (RR, 6.38; P <.001), diarrhea (RR, 2.57; P =.002) and fatigue (RR, 1.35; P <.001). Conclusions: The addition of a VEGFR or EGFR-family TKI to chemotherapy in solid cancers increases the risk of severe toxicities and treatment discontinuations. These findings might explain the general lack of a survival benefit with these regimens.

scholarly journals A Comprehensive Evaluation Between Dexmedetomidine and Midazolam for Intraoperative Sedation in the Elderly: Protocol for a Systematic Review and Meta-analysis of Randomized Controlled Trials

2021 ◽  
Author(s):  
Chunxia Huang ◽  
Zunjiang Li ◽  
Yingxin Long ◽  
Dongli Li ◽  
Manhua Huang ◽  
...  
Keyword(s):  
Systematic Review ◽  
Randomized Controlled Trials ◽  
Meta Analysis ◽  
The Elderly ◽  
Sedative Effect ◽  
Controlled Trials ◽  
Safety And Efficacy ◽  
Quality Of Evidence ◽  
Randomized Controlled

Abstract Background: The sedative effect of intraoperative sedation in elderly surgery exerts critical influence on the prognosis. Comparison on the safety and efficacy between Dexmedetomidine and Midazolam in many clinical randomized controlled trials (RCTs) were inconsistent and suspicious. We aimed to comprehensively evaluate the safety and efficacy between Dexmedetomidine and Midazolam for intraoperative sedation in the elderly via meta-analysis and systematic reviews.Methods: RCTs regarding to the comparison of sedative effects and safety between Dexmedetomidine and Midazolam in elderly patients (aged ≥ 60 years) will be comprehensively searched from 2000.10 to 2021.05 through 4 English databases and 4 Chinese databases. After extraction in duplicate, the systematic review and meta-analysis will be performed on the primary outcomes (hemodynamic changes, sedative effect, cognitive function) and secondary outcomes (analgesic effect, surgical characteristics, complications or adverse reactions) for assessing the two therapy methods using Review manage software (Version 5.3). Sensitivity analysis will be conducted to evaluate the heterogeneity of the results, funnel plot and Egger’s test will be performed to analyze publication bias of the included studies, and test sequential analysis will be applied to assess the robustness and reliability of preliminary meta-analysis results. Finally, rating quality of evidence and strength of recommendations on the meta results will be summarized by rating quality of evidence and strength of recommendations (GRADE) approach. Discussion: This systematic review and meta-analysis will evaluate the safety and efficacy between Dexmedetomidine and Midazolam for intraoperative sedation in the elderly, it will give an insight on the application of Dexmedetomidine and Midazolam, and will provide evidences-based reference for clinical decision makings.Systematic review registration: PROSPERO (CRD42021221897).

scholarly journals Safety and efficacy of gefapixant, a novel drug for the treatment of chronic cough: A systematic review and meta-analysis of randomized controlled trials

2021 ◽  
Vol 16 (2) ◽  
pp. 127
Author(s):  
Ahmed Abu-Zaid ◽  
AseelKhalid Aljaili ◽  
Amnah Althaqib ◽  
Fatima Adem ◽  
DoaaAli Alhalal ◽  
...  
Keyword(s):  
Systematic Review ◽  
Randomized Controlled Trials ◽  
Chronic Cough ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Safety And Efficacy ◽  
Randomized Controlled ◽  
Novel Drug

scholarly journals Safety and efficacy of active and passive immunotherapy in mild-to-moderate Alzheimer’s disease: A systematic review and network meta-analysis

2019 ◽  
Vol 42 (1) ◽  
pp. E53-E65 ◽  
Author(s):  
Naghmeh Foroutan ◽  
Robert B. Hopkins ◽  
Jean-Eric Tarride ◽  
Ivan D. Florez ◽  
Mitchell Levine
Keyword(s):  
Systematic Review ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Randomized Controlled Trials ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Controlled Trials ◽  
Safety And Efficacy ◽  
Randomized Controlled ◽  
Clinically Significant

Objective: The objective of this study was to systematically review and conduct a direct and network meta-analysis of randomized controlled trials that have examined the clinical safety and efficacy of using passive and active immunotherapies in Alzheimer’s disease (AD). Research questions: (1) Is amyloid-based immunotherapy in patients with mild-to-moderate AD associated with more efficacy benefits compared to placebo? (2) Which immunotherapy agent is associated with more comparative benefit? (3) Is passive or active immunotherapy associated with more benefits? Data sources: A systematic review of published randomized controlled trials was performed in MEDLINE, EMBASE, PubMed and Cochrane library. Review methods and meta-analysis: Two reviewers independently selected the studies, extracted the data and assessed risk of bias. Important AD cognitive scales as clinical efficacy outcomes were ADAS-cog, CDR and MMSE whereas edema, neoplasms and mortality were included as safety outcomes. A direct comparison meta-analysis using a random effect model and a network (direct and indirect) comparison was conducted to calculate mean differences in treatment effects, SUCRA and ranking probabilities for each medicine per safety and efficacy outcome. Quality of network results were assessed using GRADE methodology. Principle findings: Thirteen RCT-assessed patients with mild-to-moderate AD were included in the final analysis. The results showed that immunotherapies compared with placebo produced a statistically, but not clinically significant, improvement in ADAS-cog (MD=-0.39; 95% CI -0.42, -0.35, P=0.00) and MMSE. In terms of safety, the rate of ARIA-E was significantly higher with monoclonal antibodies. Solanezumab and AN1792 (vaccine) were the drugs of choice both from efficacy and safety perspectives. Conclusion: In terms of efficacy, the review showed a statistically, but not clinically significant, improvement in favor of immunotherapy versus placebo. Further clinical trials are required to demonstrate any cognitive benefits of immunotherapies in mild-to-moderate AD.

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