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Photodiagnosis and Photodynamic Therapy Mar 2020Any successful endodontic therapy requires elimination of the endodontic biofilms through meticulous root canal disinfection methods. Sodium hypochlorite (NaOCl) and... (Review)
Review
BACKGROUND
Any successful endodontic therapy requires elimination of the endodontic biofilms through meticulous root canal disinfection methods. Sodium hypochlorite (NaOCl) and ethylenediaminetetraacetic acid (EDTA) are the most common effective irrigants, in removing smear-layer from the coronal and middle thirds of the dental canals but reduced considerably towards the apical one third. In recent years, newly alternative treatment modalities have been proposed, including high-power lasers and antimicrobial photodynamic therapy (aPDT). Our work was conducted to evalaute the outcome of root canal disinfection in relation to the efficacy of various treatment modalities. Furthermore, every effort was made to present an overview of the aPDT outcomes, as a model for this application, and to propose laser parameters protocol with positive results.
METHODS
The electronic databases PubMed was searched from January 2013- January 2019. Our inclusive criteria based on laser therapy applications, as a model for root canal disinfection. The search terms utilised various combinations as follows: photodynamic therapy or antimicrobial photodynamic therapy or photoactivated disinfection or light activated disinfection or laser activated disinfection or laser therapy, and endodontic.
RESULTS
The results of this systematic review concluded that the effectiveness of aPDT and various laser wavelengths protocols, in removing endodontic biofilms from infected root canals, remains unattainable.
CONCLUSIONS
Study concluded that the combination of aPDT with antimicrobial irrigants could provide a synergetic effect. However, due to the heterogeneity of the selected studies and their limitations, in terms of lack of standardised protocol or discrepancy in the methodology, authors suggest further validated approaches to achieve optimal outcomes.
Topics: Dental Pulp Cavity; Disinfection; Enterococcus faecalis; Photochemotherapy; Photosensitizing Agents; Root Canal Irrigants; Root Canal Preparation; Sodium Hypochlorite
PubMed: 31809911
DOI: 10.1016/j.pdpdt.2019.101611 -
Journal of Veterinary Emergency and... Jan 2019To systematically review available evidence and establish guidelines related to the risk of developing thrombosis and the management of small animals with...
American College of Veterinary Emergency and Critical Care (ACVECC) Consensus on the Rational Use of Antithrombotics in Veterinary Critical Care (CURATIVE) guidelines: Small animal.
OBJECTIVES
To systematically review available evidence and establish guidelines related to the risk of developing thrombosis and the management of small animals with antithrombotics.
DESIGN
Standardized, systematic evaluation of the literature (identified by searching Medline via PubMed and CAB abstracts) was carried out in 5 domains (Defining populations at risk; Defining rational therapeutic use; Defining evidence-based protocols; Refining and monitoring antithrombotic therapies; and Discontinuing antithrombotic therapies). Evidence evaluation was carried out using Population, Intervention, Comparison, Outcome generated within each domain questions to address specific aims. This was followed by categorization of relevant articles according to level of evidence and quality (Good, Fair, or Poor). Synthesis of these data led to the development of a series of statements. Consensus on the final guidelines was achieved via Delphi-style surveys. Draft recommendations were presented at 2 international veterinary conferences and made available for community assessment, review, and comment prior to final revisions and publication.
SETTINGS
Academic and referral veterinary medical centers.
RESULTS
Over 500 studies were reviewed in detail. Worksheets from all 5 domains generated 59 statements with 83 guideline recommendations that were refined during 3 rounds of Delphi surveys. A high degree of consensus was reached across all guideline recommendations.
CONCLUSIONS
Overall, systematic evidence evaluations yielded more than 80 recommendations for the treatment of small animals with or at risk of developing thrombosis. Numerous significant knowledge gaps were highlighted by the evidence reviews undertaken, indicating the need for substantial additional research in this field.
Topics: Animals; Cat Diseases; Cats; Critical Care; Delphi Technique; Dog Diseases; Dogs; Fibrinolytic Agents; Practice Patterns, Physicians'; Thrombosis; Veterinary Medicine
PubMed: 30654421
DOI: 10.1111/vec.12801 -
The Cochrane Database of Systematic... Dec 2020The use of insulin-sensitising agents, such as metformin, in women with polycystic ovary syndrome (PCOS) who are undergoing ovulation induction or in vitro fertilisation... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The use of insulin-sensitising agents, such as metformin, in women with polycystic ovary syndrome (PCOS) who are undergoing ovulation induction or in vitro fertilisation (IVF) cycles has been widely studied. Metformin reduces hyperinsulinaemia and suppresses the excessive ovarian production of androgens. It is suggested that as a consequence metformin could improve assisted reproductive techniques (ART) outcomes, such as ovarian hyperstimulation syndrome (OHSS), pregnancy, and live birth rates.
OBJECTIVES
To determine the effectiveness and safety of metformin as a co-treatment during IVF or intracytoplasmic sperm injection (ICSI) in achieving pregnancy or live birth in women with PCOS.
SEARCH METHODS
We searched the Cochrane Gynaecology and Fertility Group Specialised Register, CENTRAL via the Cochrane Register of Studies Online (CRSO), MEDLINE, Embase, PsycINFO, LILACS, the trial registries for ongoing trials, and reference lists of articles (from inception to 13 February 2020).
SELECTION CRITERIA
Types of studies: randomised controlled trials (RCTs) comparing metformin treatment with placebo or no treatment in women with PCOS who underwent IVF or ICSI treatment.
TYPES OF PARTICIPANTS
women of reproductive age with anovulation due to PCOS with or without co-existing infertility factors. Types of interventions: metformin administered before and during IVF or ICSI treatment.
PRIMARY OUTCOME MEASURES
live birth rate, incidence of ovarian hyperstimulation syndrome.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected the studies, extracted the data according to the protocol, and assessed study quality. We assessed the overall quality of the evidence using the GRADE approach.
MAIN RESULTS
This updated review includes 13 RCTs involving a total of 1132 women with PCOS undergoing IVF/ICSI treatments. We stratified the analysis by type of ovarian stimulation protocol used (long gonadotrophin-releasing hormone agonist (GnRH-agonist) or short gonadotrophin-releasing hormone antagonist (GnRH-antagonist)) to determine whether the type of stimulation used influenced the outcomes. We did not perform meta-analysis on the overall (both ovarian stimulation protocols combined) data for the outcomes of live birth and clinical pregnancy rates per woman because of substantial heterogeneity. In the long protocol GnRH-agonist subgroup, the pooled evidence showed that we are uncertain of the effect of metformin on live birth rate per woman when compared with placebo/no treatment (risk ratio (RR) 1.30, 95% confidence interval (CI) 0.94 to 1.79; 6 RCTs; 651 women; I = 47%; low-quality evidence). This suggests that if the chance for live birth following placebo/no treatment is 28%, the chance following metformin would be between 27% and 51%. Only one study used short protocol GnRH-antagonist and reported live birth rate. Metformin may reduce live birth rate compared with placebo/no treatment (RR 0.48, 95% CI 0.29 to 0.79; 1 RCT; 153 women; low-quality evidence). This suggests that if the chance for live birth following placebo/no treatment is 43%, the chance following metformin would be between 13% and 34% (short GnRH-antagonist protocol). We found that metformin may reduce the incidence of OHSS (RR 0.46, 95% CI 0.29 to 0.72; 11 RCTs; 1091 women; I = 38%; low-quality evidence). This suggests that for a woman with a 20% risk of OHSS without metformin, the corresponding risk using metformin would be between 6% and 14%. Using long protocol GnRH-agonist stimulation, metformin may increase clinical pregnancy rate per woman compared with placebo/no treatment (RR 1.32, 95% CI 1.08 to 1.63; 10 RCTs; 915 women; I = 13%; low-quality evidence). Using short protocol GnRH-antagonist, we are uncertain of the effect of metformin on clinical pregnancy rate per woman compared with placebo/no treatment (RR 1.38, 95% CI 0.21 to 9.14; 2 RCTs; 177 women; I = 87%; very low-quality evidence). We are uncertain of the effect of metformin on miscarriage rate per woman when compared with placebo/no treatment (RR 0.86, 95% CI 0.56 to 1.32; 8 RCTs; 821 women; I = 0%; low-quality evidence). Metformin may result in an increase in side effects compared with placebo/no treatment (RR 3.35, 95% CI 2.34 to 4.79; 8 RCTs; 748 women; I = 0%; low-quality evidence). The overall quality of evidence ranged from very low to low. The main limitations were inconsistency, risk of bias, and imprecision.
AUTHORS' CONCLUSIONS
This updated review on metformin versus placebo/no treatment before or during IVF/ICSI treatment in women with PCOS found no conclusive evidence that metformin improves live birth rates. In a long GnRH-agonist protocol, we are uncertain whether metformin improves live birth rates, but metformin may increase the clinical pregnancy rate. In a short GnRH-antagonist protocol, metformin may reduce live birth rates, although we are uncertain about the effect of metformin on clinical pregnancy rate. Metformin may reduce the incidence of OHSS but may result in a higher incidence of side effects. We are uncertain of the effect of metformin on miscarriage rate per woman.
Topics: Abortion, Spontaneous; Bias; Confidence Intervals; Female; Fertilization in Vitro; Humans; Hyperandrogenism; Hyperinsulinism; Hypoglycemic Agents; Live Birth; Metformin; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Placebos; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Rate; Randomized Controlled Trials as Topic; Sperm Injections, Intracytoplasmic
PubMed: 33347618
DOI: 10.1002/14651858.CD006105.pub4 -
The American Journal of Emergency... Jan 2022Safe and effective tranquilization of the acutely agitated patient is challenging, and head-to-head comparisons of medications are limited. We aimed to identify the most... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Safe and effective tranquilization of the acutely agitated patient is challenging, and head-to-head comparisons of medications are limited. We aimed to identify the most optimal agent(s) for rapid tranquilization of the severely agitated patient in the emergency department (ED).
METHODS
The protocol for systematic review was registered (PROSPERO; CRD42020212534). We searched MEDLINE, Embase, PsycINFO, and Cochrane Database/CENTRAL from inception to June 2, 2021. We limited studies to randomized controlled trials that enrolled adult ED patients with severe agitation and compared drugs for rapid tranquilization. Predetermined outcomes were: 1) Adequate sedation within 30 min (effectiveness), 2) Immediate, serious adverse event - cardiac arrest, ventricular tachydysrhythmia, endotracheal intubation, laryngospasm, hypoxemia, hypotension (safety), and 3) Time to adequate sedation (effect onset). We extracted data according to PRISMA-NMA and appraised trials using Cochrane RoB 2 tool. We performed Bayesian network meta-analysis (NMA) using a Markov Chain Monte Carlo method with random-effects model and vague prior distribution to calculate odds ratios with 95% credible intervals for dichotomous outcomes and frequentist NMA to calculate mean differences with 95% confidence intervals for continuous outcomes. We assessed confidence in results using CINeMA. We used surface under the cumulative ranking (SUCRA) curves to rank agent(s) for each outcome.
RESULTS
Eleven studies provided data for effectiveness (1142 patients) and safety (1147 patients). Data was insufficient for effect onset. The NMA found that ketamine (SUCRA = 93.0%) is most likely to have superior effectiveness; droperidol-midazolam (SUCRA = 78.8%) is most likely to be safest. There are concerns with study quality and imprecision. Quality of the point estimates varied for effectiveness but mostly rated "very low" for safety.
CONCLUSIONS
Available evidence suggests that ketamine and droperidol have intermediate effectiveness for rapid tranquilization of the severely agitated patient in the ED. There is insufficient evidence to definitively determine which agent(s) may be safest or fastest-acting. Further, direct-comparison study of ketamine and droperidol is recommended.
Topics: Adult; Droperidol; Emergence Delirium; Emergency Service, Hospital; Humans; Ketamine; Network Meta-Analysis; Psychomotor Agitation; Randomized Controlled Trials as Topic; Severity of Illness Index; Treatment Outcome
PubMed: 34823192
DOI: 10.1016/j.ajem.2021.11.011 -
Cancer Science Jul 2021Chemotherapy for non-Hodgkin lymphoma (NHL) in the hemodialysis (HD) patient is a challenging situation. Because many drugs are predominantly eliminated by the kidneys,...
Chemotherapy for non-Hodgkin lymphoma (NHL) in the hemodialysis (HD) patient is a challenging situation. Because many drugs are predominantly eliminated by the kidneys, chemotherapy in the HD patient requires special considerations concerning dose adjustments to avoid overdose and toxicities. Conversely, some drugs are removed by HD and may expose the patient to undertreatment, therefore the timing of drug administration in relation to HD sessions must be carefully planned. Also, the metabolites of some drugs show different toxicities and dialysability as compared with the parent drug, therefore this must also be catered for. However, the pharmacokinetics of many chemotherapeutics and their metabolites in HD patients are unknown, and the fact that NHL patients are often treated with distinct multiagent chemotherapy regimens makes the situation more complicated. In a realm where uncertainty prevails, case reports and case series reporting on actual treatment and outcomes are extremely valuable and can aid physicians in decision making from drug selection to dosing. We carried out an exhaustive review of the literature and adopted 48 manuscripts consisting of 66 HD patients undergoing 71 chemotherapy regimens for NHL, summarized the data, and provide recommendations concerning dose adjustments and timing of administration for individual chemotherapeutics where possible. The chemotherapy regimens studied in this review include, but are not limited to, rituximab, cyclophosphamide + vincristine + prednisolone (CVP) and cyclophosphamide + doxorubicin + vincristine + prednisolone (CHOP)-like regimens, chlorambucil, ibrutinib, bendamustine, methotrexate, platinum compounds, cytarabine, gemcitabine, etoposide, ifosfamide, melphalan, busulfan, fludarabine, mogamulizumab, brentuximab vedotin, and Y-ibritumomab tiuxetan.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Child; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Female; Hematopoietic Stem Cell Transplantation; Humans; Kidney; Lymphoma, Non-Hodgkin; Male; Middle Aged; Prednisone; Renal Dialysis; Rituximab; Vincristine; Young Adult
PubMed: 33938097
DOI: 10.1111/cas.14933 -
International Forum of Allergy &... Jan 2024The heterogeneity of existing studies, along with the fact that there are no published head-to-head trials, are the main reasons for the lack of guidelines regarding the... (Review)
Review
Chronic rhinosinusitis with nasal polyps (CRSwNP) treated with omalizumab, dupilumab, or mepolizumab: A systematic review of the current knowledge towards an attempt to compare agents' efficacy.
BACKGROUND
The heterogeneity of existing studies, along with the fact that there are no published head-to-head trials, are the main reasons for the lack of guidelines regarding the selection of the proper biologic in treatment of chronic rhinosinusitis (CRS) with nasal polyps. The aim of this study is to summarize the current knowledge regarding the efficacy of omalizumab, dupilumab, and mepolizumab in CRS treatment. We also attempt to proceed to an indirect comparison of the agents and try to answer the tricky question: which agent to select and why?
METHODS
An extensive search in English literature was conducted in PubMed/Medline, Embase, Google Scholar, and Cochrane Database/Library. Eligibility criteria included papers with full text published in English, adult population studies, clearly described intervention protocol, and documented primary and secondary outcomes.
RESULTS
The studies included numbered 37. All agents provided significant improvement in polyp size, sinuses opacification, severity of symptoms, need for surgery and systemic corticosteroids use. Analysis of available systematic reviews, meta-analyses and indirect treatment comparison studies showed that dupilumab appeared to be the most beneficial agent, in terms of primary and secondary outcomes. However, these results are of relatively low level of evidence due to several methodological limitations.
CONCLUSIONS
Although the present analysis showed a moderate supremacy of dupilumab, there is still no evidence-based answer to the question "which biologic agent is the most effective in CRS treatment?" Improved statistical methodology, head-to-head trials, and real-life studies could lead to more robust conclusions, establishing the real role of the specific biologic agents.
Topics: Adult; Humans; Nasal Polyps; Omalizumab; Rhinosinusitis; Sinusitis; Chronic Disease; Biological Products; Rhinitis; Quality of Life; Antibodies, Monoclonal, Humanized
PubMed: 37394893
DOI: 10.1002/alr.23234 -
International Journal of Epidemiology Oct 2006The association between parental exposure to Agent Orange or dioxin and birth defects is controversial, due to inconsistent findings in the literature. The principal aim... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The association between parental exposure to Agent Orange or dioxin and birth defects is controversial, due to inconsistent findings in the literature. The principal aim of this study was to conduct a meta-analysis of relevant epidemiological studies that examined this association and to assess the heterogeneity among studies.
METHODS
Relevant studies were identified through a computerized literature search of Medline and Embase from 1966 to 2002; reviewing the reference list of retrieved articles and conference proceedings; and contacting researchers for unpublished studies. A specified protocol was followed to extract data on study details and outcomes. Both fixed-effects and random-effects models were used to synthesize the results of individual studies. The Cochrane Q test and index of heterogeneity (I2) were used to evaluate heterogeneity, and a funnel plot and Egger's test were used to evaluate publication bias.
RESULTS
In total, 22 studies including 13 Vietnamese and nine non-Vietnamese studies were identified. The summary relative risk (RR) of birth defects associated with exposure to Agent Orange was 1.95 [95% confidence interval (95% CI) 1.59-2.39], with substantial heterogeneity across studies. Vietnamese studies showed a higher summary RR (RR = 3.00; 95% CI 2.19-4.12) than non-Vietnamese studies (RR = 1.29; 95% CI 1.04-1.59). Sub-group analyses found that the magnitude of association tended to increase with greater degrees of exposure to Agent Orange, rated on intensity and duration of exposure and dioxin concentrations measured in affected populations.
CONCLUSION
Parental exposure to Agent Orange appears to be associated with an increased risk of birth defects.
Topics: 2,4,5-Trichlorophenoxyacetic Acid; 2,4-Dichlorophenoxyacetic Acid; Abnormalities, Drug-Induced; Agent Orange; Defoliants, Chemical; Female; Humans; Infant, Newborn; Male; Maternal Exposure; Paternal Exposure; Polychlorinated Dibenzodioxins; Pregnancy; Prenatal Exposure Delayed Effects; Vietnam
PubMed: 16543362
DOI: 10.1093/ije/dyl038 -
Expert Opinion on Investigational Drugs Jun 2008Enzastaurin is a novel antineoplastic and antiangiogenic agent that acts through inhibition of protein kinase C (PKC). (Review)
Review
BACKGROUND
Enzastaurin is a novel antineoplastic and antiangiogenic agent that acts through inhibition of protein kinase C (PKC).
OBJECTIVE
This review summarizes the scientific rationale and current clinical evidence for the use of enzastaurin in oncology.
METHODS
We performed a systematic review of the literature using the keywords protein kinase C-beta and enzastaurin in order to characterize the therapeutic target PKC-beta. We then reviewed the in-vitro, Phase I, and Phase II data for enzastaurin with a focus on hematologic malignancies.
RESULTS/CONCLUSIONS
After preliminary Phase I trials established a favorable toxicity profile, enzastaurin has been studied in completed and ongoing Phase II and III studies in solid and hematologic malignancies, including B-cell lymphomas where the rationale for its use is most promising.
Topics: Angiogenesis Inhibitors; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Clinical Trials as Topic; Enzyme Activation; Humans; Indoles; Neoplasm Invasiveness; Neoplasm Proteins; Neoplasms; Neovascularization, Pathologic; Phosphoinositide-3 Kinase Inhibitors; Phosphorylation; Protein Kinase C; Protein Kinase C beta; Protein Kinase Inhibitors; Protein Processing, Post-Translational; Proto-Oncogene Proteins c-akt; Salvage Therapy; Signal Transduction; Vascular Endothelial Growth Factor A
PubMed: 18491994
DOI: 10.1517/13543784.17.6.939 -
The Cochrane Database of Systematic... Apr 2021Immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis have changed the first-line treatment of people with advanced non-small cell lung cancer (NSCLC).... (Meta-Analysis)
Meta-Analysis
Single or combined immune checkpoint inhibitors compared to first-line platinum-based chemotherapy with or without bevacizumab for people with advanced non-small cell lung cancer.
BACKGROUND
Immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis have changed the first-line treatment of people with advanced non-small cell lung cancer (NSCLC). Single-agent pembrolizumab (a PD-1 inhibitor) is currently the standard of care as monotherapy in patients with PD-L1 expression ≥ 50%, either alone or in combination with chemotherapy when PD-L1 expression is less than 50%. Atezolizumab (PD-L1 inhibitor) has also been approved in combination with chemotherapy and bevacizumab (an anti-angiogenic antibody) in first-line NSCLC regardless of PD-L1 expression. The combination of first-line PD-1/PD-L1 inhibitors with anti-CTLA-4 antibodies has also been shown to improve survival compared to platinum-based chemotherapy in advanced NSCLC, particularly in people with high tumour mutational burden (TMB). The association of ipilimumab (an anti CTLA4) and nivolumab (PD-1 inhibitor) has been approved by the US Food and Drug Administration (FDA) in all patients with PD-L1 expression ≥1%. Although these antibodies are currently used in clinical practice, some questions remain unanswered, such as the best-treatment strategy, the role of different biomarkers for treatment selection and the effectiveness of immunotherapy according to specific clinical characteristics.
OBJECTIVES
To determine the effectiveness and safety of first-line immune checkpoint inhibitors (ICIs), as monotherapy or in combination, compared to platinum-based chemotherapy, with or without bevacizumab for people with advanced NSCLC, according to the level of PD-L1 expression.
SEARCH METHODS
We performed an electronic search of the main databases (Cochrane Central Register of Controlled Trials, MEDLINE, Embase) from inception until 31 December 2020 and conferences meetings from 2015 onwards.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) reporting on the efficacy or safety of first-line ICI treatment for adults with advanced NSCLC who had not previously received any anticancer treatment. We included trials comparing single- or double-ICI treatment to standard first-line therapy (platinum-based chemotherapy +/- bevacizumab). All data come from 'international multicentre studies involving adults, age 18 or over, with histologically-confirmed stage IV NSCLC.
DATA COLLECTION AND ANALYSIS
Three review authors independently assessed the search results and a fourth review author resolved any disagreements. Primary outcomes were overall survival (OS) and progression-free survival (PFS); secondary outcomes were overall objective response rate (ORR) by RECIST v 1.1, grade 3 to 5 treatment-related adverse events (AEs) (CTCAE v 5.0) and health-related quality of life (HRQoL). We performed meta-analyses where appropriate using the random-effects model for hazard ratios (HRs) or risk ratios (RRs), with 95% confidence intervals (95% CIs), and used the I² statistic to investigate heterogeneity.
MAIN RESULTS
Main results We identified 15 trials for inclusion, seven completed and eight ongoing trials. We obtained data for 5893 participants from seven trials comparing first-line single- (six trials) or double- (two trials) agent ICI with platinum-based chemotherapy, one trial comparing both first-line single- and double-agent ICsI with platinum-based chemotherapy. All trials were at low risk of selection and detection bias, some were classified at high risk of performance, attrition or other source of bias. The overall certainty of evidence according to GRADE ranged from moderate-to-low because of risk of bias, inconsistency, or imprecision. The majority of the included trials reported their outcomes by PD-L1 expressions, with PD-L1 ≥ 50 being considered the most clinically useful cut-off level for decision makers. Also, iIn order to avoid overlaps between various PDL-1 expressions we prioritised the review outcomes according to PD-L1 ≥ 50. Single-agent ICI In the PD-L1 expression ≥ 50% group single-agent ICI probably improved OS compared to platinum-based chemotherapy (hazard ratio (HR) 0.68, 95% confidence interval (CI) 0.60 to 0.76, 6 RCTs, 2111 participants, moderate-certainty evidence). In this group, single-agent ICI also may improve PFS (HR: 0.68, 95% CI 0.52 to 0.88, 5 RCTs, 1886 participants, low-certainty evidence) and ORR (risk ratio (RR):1.40, 95% CI 1.12 to 1.75, 4 RCTs, 1672 participants, low-certainty evidence). HRQoL data were available for only one study including only people with PD-L1 expression ≥ 50%, which suggested that single-agent ICI may improve HRQoL at 15 weeks compared to platinum-based chemotherapy (RR: 1.51, 95% CI 1.08 to 2.10, 1 RCT, 297 participants, low-certainty evidence). In the included studies, treatment-related AEs were not reported according to PD-L1 expression levels. Grade 3-4 AEs may be less frequent with single-agent ICI compared to platinum-based chemotherapy (RR: 0.41, 95% CI 0.33 to 0.50, I² = 62%, 5 RCTs, 3346 participants, low-certainty evidence). More information about efficacy of single-agent ICI compared to platinum-based chemotherapy according to the level of PD-L1 expression and to TMB status or specific clinical characteristics is available in the full text. Double-agent ICI Double-ICI treatment probably prolonged OS compared to platinum-based chemotherapy in people with PD-L1 expression ≥50% (HR: 0.72, 95% CI 0.59 to 0.89 2 RCTs, 612 participants, moderate-certainty evidence). Trials did not report data on HRQoL, PFS and ORR according to PD-L1 groups. Treatment related AEs were not reported according to PD-L1 expression levels. The frequency of grade 3-4 AEs may not differ between double-ICI treatment and platinum-based chemotherapy (RR: 0.78, 95% CI 0.55 to 1.09, I² = 81%, 2 RCTs, 1869 participants, low-certainty evidence). More information about efficacy of double-agent ICI according to the level of PD-L1 expression and to TMB status is available in the full text.
AUTHORS' CONCLUSIONS
Authors' conclusions The evidence in this review suggests that single-agent ICI in people with NSCLC and PD-L1 ≥50% probably leads to a higher overall survival rate and may lead to a higher progression-free survival and overall response rate when compared to platinum-based chemotherapy and may also lead to a lower rate of adverse events and higher HRQoL. Combined ICI in people with NSCLC and PD-L1 ≥50% also probably leads to a higher overall survival rate when compared to platinum-based chemotherapy, but its effect on progression-free survival, overall response rate and HRQoL is unknown due to a lack of data. The rate of adverse events may not differ between groups. This review used to be a living review. It is transitioned out of living mode because current research is exploring ICI in association with chemotherapy or other immunotherapeutic drugs versus ICI as single agent rather than platinum based chemotherapy.
Topics: Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; B7-H1 Antigen; Bevacizumab; Bias; Carcinoma, Non-Small-Cell Lung; Female; Humans; Immune Checkpoint Inhibitors; Lung Neoplasms; Male; Middle Aged; Nivolumab; Platinum Compounds; Progression-Free Survival; Randomized Controlled Trials as Topic
PubMed: 33930176
DOI: 10.1002/14651858.CD013257.pub3 -
Cancer Treatment Reviews Feb 2018Despite a lack of improvement in overall survival (OS) with doxorubicin-based combinations over doxorubicin alone in advanced STS, the role of multi-agent chemotherapy... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Despite a lack of improvement in overall survival (OS) with doxorubicin-based combinations over doxorubicin alone in advanced STS, the role of multi-agent chemotherapy remains poorly defined.
METHODS
We conducted a systematic review and meta-analysis to evaluate benefits and harms of multi-agent chemotherapy in advanced STS. Eligible studies were randomized trials of chemotherapy in advanced STS comparing single agent to multi-agent therapy. Data from studies reporting a hazard ratio (HR) and 95% confidence intervals (CI) for OS and progression-free survival (PFS) were pooled in a meta-analysis. Meta-regression was utilized to explore the association between efficacy (OS and PFS) and both toxicity and dose intensity.
RESULTS
We identified 22 trials published between 1974 and April 2016 and comprising 5044 patients. Overall, multi-agent chemotherapy was associated with improved OS (HR:0.79, p = 0.02), and borderline improvement in PFS (HR:0.86, p = 0.05). While the effect on OS was similar in trials with non-anthracycline controls compared to those with anthracycline controls (HR for OS 0.73 vs. 0.82, p for difference = 0.63) there was a non-significantly greater effect for multi-agent chemotherapy on PFS in non-anthracycline RCT (HR for PFS 0.73 vs. 0.91, p for difference = 0.13). Compared to studies with cytotoxic therapy-based multi-agent therapy, a non-significantly greater magnitude of effect among studies with biological/cytostatic experimental groups was seen (HR for OS 0.64 vs. 0.86, p for difference = 0.37). There was a borderline significant association between dose reductions (which were more common in combination arms) and worse PFS (beta = 0.70, p = 0.053).
CONCLUSION
Multi-agent chemotherapy is associated with a modest, but statistically significant improvement in outcomes in STS. Combining chemotherapy with non-cytotoxic agents might represent a promising strategy.
Topics: Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Disease-Free Survival; Doxorubicin; Humans; Randomized Controlled Trials as Topic; Sarcoma
PubMed: 29253836
DOI: 10.1016/j.ctrv.2017.12.003