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The Lancet. Oncology Sep 2013Several treatment strategies are available for adults with advanced-stage Hodgkin's lymphoma, but studies assessing two alternative standards of care-increased dose... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Several treatment strategies are available for adults with advanced-stage Hodgkin's lymphoma, but studies assessing two alternative standards of care-increased dose bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPPescalated), and doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD)-were not powered to test differences in overall survival. To guide treatment decisions in this population of patients, we did a systematic review and network meta-analysis to identify the best initial treatment strategy.
METHODS
We searched the Cochrane Library, Medline, and conference proceedings for randomised controlled trials published between January, 1980, and June, 2013, that assessed overall survival in patients with advanced-stage Hodgkin's lymphoma given BEACOPPbaseline, BEACOPPescalated, BEACOPP variants, ABVD, cyclophosphamide (mechlorethamine), vincristine, procarbazine, and prednisone (C[M]OPP), hybrid or alternating chemotherapy regimens with ABVD as the backbone (eg, COPP/ABVD, MOPP/ABVD), or doxorubicin, vinblastine, mechlorethamine, vincristine, bleomycin, etoposide, and prednisone combined with radiation therapy (the Stanford V regimen). We assessed studies for eligibility, extracted data, and assessed their quality. We then pooled the data and used a Bayesian random-effects model to combine direct comparisons with indirect evidence. We also reconstructed individual patient survival data from published Kaplan-Meier curves and did standard random-effects Poisson regression. Results are reported relative to ABVD. The primary outcome was overall survival.
FINDINGS
We screened 2055 records and identified 75 papers covering 14 eligible trials that assessed 11 different regimens in 9993 patients, providing 59 651 patient-years of follow-up. 1189 patients died, and the median follow-up was 5·9 years (IQR 4·9-6·7). Included studies were of high methodological quality, and between-trial heterogeneity was negligible (τ(2)=0·01). Overall survival was highest in patients who received six cycles of BEACOPPescalated (HR 0·38, 95% credibility interval [CrI] 0·20-0·75). Compared with a 5 year survival of 88% for ABVD, the survival benefit for six cycles of BEACOPPescalated is 7% (95% CrI 3-10)-ie, a 5 year survival of 95%. Reconstructed individual survival data showed that, at 5 years, BEACOPPescalated has a 10% (95% CI 3-15) advantage over ABVD in overall survival.
INTERPRETATION
Six cycles of BEACOPPescalated significantly improves overall survival compared with ABVD and other regimens, and thus we recommend this treatment strategy as standard of care for patients with access to the appropriate supportive care.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Dacarbazine; Doxorubicin; Etoposide; Hodgkin Disease; Humans; Prednisone; Procarbazine; Vinblastine; Vincristine
PubMed: 23948348
DOI: 10.1016/S1470-2045(13)70341-3 -
Archives of Disease in Childhood Feb 2009To determine the benefits and harms of therapies used to prevent or treat renal involvement in Henoch-Schönlein purpura. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To determine the benefits and harms of therapies used to prevent or treat renal involvement in Henoch-Schönlein purpura.
DESIGN
Systematic review of randomised controlled trials.
SETTING
Secondary and tertiary paediatric and paediatric nephrology services.
SUBJECTS
Ten trials involving 1230 children aged less than 18 years.
MAIN OUTCOME MEASURES
Persistent proteinuria and/or haematuria.
RESULTS
Meta-analyses of four trials showed no significant difference in the risk of persistent kidney disease at 6 months (379 children; relative risk (RR) 0.51, 95% CI 0.24 to 1.11) and 12 months (498 children; RR 1.02, 95% CI 0.40 to 2.62) in children given prednisone for 14-28 days at presentation of Henoch-Schönlein purpura compared with placebo or supportive treatment. In children with severe renal disease, there was no significant difference in the risk of persistent renal disease with cyclophosphamide compared with supportive treatment (one trial; 56 children; RR 1.07, 95% CI 0.65 to 1.78) and with cyclosporin compared with methylprednisolone (one trial; 19 children; RR 0.39; 95% CI 0.14 to 1.06).
CONCLUSIONS
Data from randomised trials for any intervention used to improve renal outcomes in children with Henoch-Schönlein purpura are very sparse except for short-term prednisone, which has not been shown to be effective.
Topics: Glucocorticoids; Hematuria; Humans; IgA Vasculitis; Immunosuppressive Agents; Kidney Diseases; Platelet Aggregation Inhibitors; Proteinuria; Randomized Controlled Trials as Topic; Research Design
PubMed: 18701559
DOI: 10.1136/adc.2008.141820 -
Medicine May 2016There are conflicts on whether influenza vaccinated systemic lupus erythematosus (SLE) patients are associated with a decreased immunogenicity and safety, compared with... (Meta-Analysis)
Meta-Analysis Review
There are conflicts on whether influenza vaccinated systemic lupus erythematosus (SLE) patients are associated with a decreased immunogenicity and safety, compared with healthy controls. We conducted meta-analyses to compare SLE patients with healthy controls for flu-vaccine immunogenicity, as well as for adverse events.PubMed, MEDLINE, and Cochrane Library were searched by October 15, 2015. Studies were included when they met the inclusion criteria. Two reviewers independently extracted data on study characteristics, methodological quality, and outcomes. The primary outcome was seroprotection (SP) rate after immunization.A total of 15 studies were included. There were significant differences in SP rates between the SLE patients and healthy controls, respectively, for H1N1 (RR 0.79, 95% CI 0.73-0.87) and B strain (RR 0.75, 95% CI 0.65-0.87), but not for H3N2 (RR 0.84, 95% CI 0.68-1.03). Subgroup analyses demonstrated SLE patients with immunosuppressants, corticosteroids, azathioprine and prednisone had significantly lower SP rates, compared with healthy controls. SLE patients with nonadjuvanted H1N1 vaccine had significantly lower SP rate, compared with healthy controls. SLE patients were not associated with increased adverse events (RR 1.88, 95% CI 0.94-3.77).SLE generates immunogenicity differently, compared with healthy controls in pandemic H1N1 and B strains, but same in seasonal H3N2 strain. Nonadjuvant and special kind of immunosuppressive biologics can play an important role in SLE immunogenicity to flu vaccine. There is no significant difference in adverse event rates between SLE patients and healthy controls.
Topics: Case-Control Studies; Humans; Immunogenicity, Vaccine; Immunosuppressive Agents; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H3N2 Subtype; Influenza Vaccines; Influenza, Human; Lupus Erythematosus, Systemic
PubMed: 27175678
DOI: 10.1097/MD.0000000000003637 -
Annales de Dermatologie Et de... Mar 2011Pemphigus is a rare autoimmune bullous disorder. Numerous treatment regimens have been proposed in the literature. (Review)
Review
BACKGROUND
Pemphigus is a rare autoimmune bullous disorder. Numerous treatment regimens have been proposed in the literature.
OBJECTIVE
To assess the efficacy and tolerance of treatment regimens proposed in pemphigus vulgaris (PV) and pemphigus foliaceus (PF), from a systematic review of the literature.
METHODS
Randomized control trials have been identified using the PubMed and Embase databases up to April 2009. Uncontrolled prospective and retrospective studies have also been analyzed.
RESULTS
Eleven randomized control trials having included a total number of 421 patients (377 PV, 44 PF) have been analyzed. Most studies had a limited statistical power due to the rather low number of cases included. Results from ten different treatment regimens have been analyzed: different dosages of prednisone and prednisolone, pulse intravenous dexamethasone, azathioprine, cyclophosphamide, cyclosporine, dapsone, mycophenolate mofetil, plasmapheresis, topical applications of epidermal growth factor (EGF), and intravenous immune globulins (IVIG). Inclusion criteria were: (i) consecutive patients in nine studies, (ii) patients who did not respond to low doses of corticosteroids in one study, and (iii) patients with relapsing type of pemphigus in one study. None of these studies allowed identifying the best effective and well tolerated regimen. Mycophenolate mofetil was more effective than azathioprine for disease control (from one study; n=40; OR=0.72; 95% CI=0.52-0.99). However, no difference in the rate of clinical remission was evidenced between these drugs. Azathioprine and cyclophosphamide seem to have a corticosteroid sparing effect.
CONCLUSION
Data from the literature did not allow identifying the best therapeutic regimen, mainly because of the lack of statistical power of most studies. The usefulness of immunosuppressant added to systemic corticosteroids as the first line of treatment is not clearly established.
Topics: Adrenal Cortex Hormones; Combined Modality Therapy; Drug Therapy, Combination; Epidermal Growth Factor; Gold Compounds; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Meta-Analysis as Topic; Multicenter Studies as Topic; Niacinamide; Paraneoplastic Syndromes; Pemphigus; Plasma Exchange; Prospective Studies; Randomized Controlled Trials as Topic; Recurrence; Retrospective Studies; Tetracycline
PubMed: 21397148
DOI: 10.1016/j.annder.2011.01.016 -
Journal of Geriatric Oncology Jun 2021Novel androgen receptor axis-targeting drugs (ARATs) have been shown to improve outcomes in men with prostate cancer. Central nervous system androgen blockade may be... (Review)
Review
CONTEXT
Novel androgen receptor axis-targeting drugs (ARATs) have been shown to improve outcomes in men with prostate cancer. Central nervous system androgen blockade may be harmful for older adults who may be at increased risk of adverse cognitive and psychologic effects.
OBJECTIVE
To systematically evaluate the effect of ARATs on cognition and depression in men with metastatic prostate cancer.
EVIDENCE ACQUISITION
We searched PubMed and EMBASE for articles published in English between September 2012 and September 2019 reporting cognition and depression outcomes in men receiving ARATs for metastatic prostate cancer using validated psychometric tools. The level of evidence and risk of bias were assessed using the GRADE approach for randomized clinical trials and observational studies.
RESULTS
15 reports studying 8954 men with metastatic castration-sensitive and -resistant, or non-metastatic castration-resistant prostate cancer were identified. Data were available for abiraterone, enzalutamide and apalutamide but not darolutamide. The mean (and 95% confidence interval) and median (and min-max) of the absolute scores and changes from baseline were included, when available. There was heterogeneity in the psychometric tools used which obviated statistical pooling of results. Very limited data assessing cognition suggested that abiraterone was associated with improved cognitive functioning or perhaps less cognitive harm versus enzalutamide. Fourteen reports assessed emotional wellbeing. ARATs reduced depressive symptoms when compared to prednisone alone or placebo but not compared to bicalutamide. Abiraterone may improve short-term emotional functioning relative to enzalutamide. The quality of evidence was low when examining ARAT effect on cognitive function and moderate when examining ARAT effect on depression.
CONCLUSIONS
Depression was assessed more frequently than cognition in men receiving ARATs. Self-reported depression measures favored abiraterone over enzalutamide and both abiraterone and enzalutamide over placebo. Data evaluating apalutamide and darolutamide are lacking. Further studies of ARATs using validated clinician-based psycho-cognition tools along with self-reported measures in men with metastatic prostate cancer are needed.
Topics: Aged; Cognition; Depression; Humans; Male; Pharmaceutical Preparations; Prostatic Neoplasms, Castration-Resistant; Receptors, Androgen; Treatment Outcome
PubMed: 33234494
DOI: 10.1016/j.jgo.2020.11.002 -
Therapeutic Advances in Medical Oncology 2022Several therapies are available for the treatment of advanced/metastatic prostate cancer (PC). However, the systematic assessment of evidence pertaining to the use of... (Review)
Review
OBJECTIVES
Several therapies are available for the treatment of advanced/metastatic prostate cancer (PC). However, the systematic assessment of evidence pertaining to the use of these therapies in Asian patients is lacking.
METHODS
A systematic literature review (SLR) was conducted using PubMed/Medline search in May 2021 to identify the randomized/nonrandomized controlled trials (RCTs/non-RCTs) and real-world observational studies (prospective/retrospective). Only studies published as full manuscripts in English were included if reporting the efficacy, effectiveness, and/or safety of treatments in Asian patients with advanced/metastatic PC.
RESULTS
Of the 1,898 retrieved publications, 24 studies were included. These studies had patients with nonmetastatic castration-resistant PC (n = 2), metastatic castration-sensitive PC ( = 4), and metastatic castration-resistant PC ( = 18). Study designs included RCTs ( = 7), non-RCTs ( = 2), and real-world studies ( = 15). Treatments used in included studies were abiraterone acetate plus prednisone (AAP; = 6), enzalutamide, lutetium-177 prostate-specific membrane antigen (Lu-PSMA; = 4 each), docetaxel ( = 3), apalutamide, radium-223 ( = 2 each), darolutamide, cabazitaxel, and pembrolizumab ( = 1 each). The evidence from RCTs (i.e., ARAMIS, SPARTAN, ARCHES, TITAN, LATITUDE, PREVAIL) demonstrated the clinical benefits of apalutamide, darolutamide, enzalutamide, and AAP in terms of overall, disease-free, and metastasis-free survival in Asian patients. These treatments were reported to be well tolerated, with no new safety signals identified in Asian population. The efficacy and safety profiles in Asian patients were consistent with the overall trial population. Data from real-world studies supported the effectiveness and tolerability of AAP, enzalutamide, radium-223, docetaxel, cabazitaxel, Lu-PSMA, and pembrolizumab in patients with advanced/metastatic PC.
CONCLUSIONS
This SLR of the Asian data on therapies for advanced PC from the pivotal and real-world studies confirms similar efficacy and safety outcomes, consistent with the results from the pivotal clinical trials. These findings will help clinicians make better treatment decisions in clinical practice for patients with advanced/metastatic PC.
PubMed: 36407784
DOI: 10.1177/17588359221131525 -
Journal of Cancer Research and Clinical... Apr 2022Smoldering multiple myeloma (SMM) is an intermediate pre-malignant condition with individuals having a distinct risk of progression to overt myeloma. The optimal... (Review)
Review
The effect of intervention versus watchful waiting on disease progression and overall survival in smoldering multiple myeloma: a systematic review of randomized controlled trials.
BACKGROUND
Smoldering multiple myeloma (SMM) is an intermediate pre-malignant condition with individuals having a distinct risk of progression to overt myeloma. The optimal management option has remained controversial due to the heterogeneous nature of the condition in which progression to overt diseases is variable. The question of who, when, and what to use for the treatment of SMM remains equivocal. We performed a systematic review of randomized controlled trials and summarized the current evidence supporting the best approach to the management of SMM.
METHODS
A comprehensive literature search of Medline/PubMed, PubMed Central, Embase, Scopus, Web of Science, Wiley Cochrane Library, CINAHL, clinicaltrial.gov, and conference proceedings of ASCO, ASH, EHA, and ESMO was performed on October 25, 2020. Synthesis of the result was done using narrative analysis.
RESULT
Of the total 1560 identified records, 10 eligible studies involving 1157 patients made up of 580 in the intervention group and 577 in the control group were included in this review. Three early trials of melphalan and prednisone fail to demonstrate any significant impact on disease progression with major toxicities reported. Three trials on bisphosphonate monotherapy show reduced skeletal-related events without any clinical effect on disease progression. Lenalidomide monotherapy or as part of a combination therapy demonstrates superiority in delaying disease progression over observation. Only Lenalidomide and dexamethasone combination demonstrated superior overall survival over observation across the trials.
CONCLUSION
Trials of lenalidomide in a less intensive approach has shown promise in delaying disease progression and should be investigated further in clinical trials.
Topics: Disease Progression; Humans; Lenalidomide; Randomized Controlled Trials as Topic; Smoldering Multiple Myeloma; Watchful Waiting
PubMed: 35059867
DOI: 10.1007/s00432-022-03920-7 -
The Journal of Rheumatology Aug 2015To determine the most effective immunosuppressive therapy for the longterm management of proliferative lupus nephritis (PLN) based on the outcome of renal failure. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To determine the most effective immunosuppressive therapy for the longterm management of proliferative lupus nephritis (PLN) based on the outcome of renal failure.
METHODS
A systematic review of randomized controlled trials (RCT) was conducted. MEDLINE and EMBASE were searched. RCT designed to examine the maintenance treatment effectiveness of immunosuppressive agents for PLN were included. A Bayesian network metaanalysis of 2-arm and 3-arm trials was used. A skeptical prior assumption was used in sensitivity analysis. Four immunosuppressive agents were evaluated: cyclophosphamide (CYC), azathioprine (AZA), mycophenolate mofetil (MMF), and prednisone alone. The outcome of interest was renal failure during the study period, defined by serum creatinine (sCr) > 256 µmol/l, doubling of sCr from baseline, and/or endstage renal disease.
RESULTS
The OR (95% credible interval) of developing renal failure at 2-3 years was 0.72 (0.11, 4.49) for AZA versus CYC, 0.32 (0.04, 2.25) for MMF versus CYC, 2.40 (0.22, 36.94) for prednisone alone versus CYC, and 0.45 (0.11, 1.48) for MMF versus AZA. The probability (95% credible interval) of developing renal failure at 2 years as expected for each agent was 6% (0.7%, 24%) for MMF, 12% (2%, 37%) for AZA, 16% (5%, 33%) for CYC, and 31% (5%, 81%) for prednisone alone. After applying a skeptical prior in the Bayesian analysis, there was no evidence of benefit for 1 therapy over another.
CONCLUSION
Although the data suggest that MMF may be superior to other treatments for the maintenance treatment of PLN, the evidence is not conclusive.
Topics: Azathioprine; Cyclophosphamide; Humans; Immunosuppressive Agents; Lupus Nephritis; Mycophenolic Acid; Prednisone; Remission Induction; Treatment Outcome
PubMed: 26077406
DOI: 10.3899/jrheum.141650 -
Deutsches Arzteblatt International Aug 2018Hodgkin lymphoma is the most common neoplasm in young adults, with an incidence of 2 to 3 cases per 100 000 persons per year. Risk-adapted chemotherapy and radiotherapy...
BACKGROUND
Hodgkin lymphoma is the most common neoplasm in young adults, with an incidence of 2 to 3 cases per 100 000 persons per year. Risk-adapted chemotherapy and radiotherapy usually lead to cure. Finding ways to lessen the treatment- associated morbidity and mortality is a major goal of current research.
METHODS
For the creation of an updated guideline (DKH grant number 111778), a systematic literature search was carried out in medical databases (MEDLINE, CENTRAL) and guideline databases (GIN) (search dates: January 2012 to June 2017).
RESULTS
Results from 10 meta-analyses, 89 randomized and controlled trials, and 81 prospective or retrospective trials were evaluated. The use of positron emission tomography (PET) is strongly recommended in the initial diagnostic evaluation, as well as for the guidance of treatment in advanced stages. In early stages, two cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) and involved-site radiotherapy (IS-RT) at a dose of 20 Gy are recommended. For the treatment of intermedi- ate stages, two cycles of escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) + two cycles of ABVD and 30 Gy IS-RT are recommended. In advanced stages, two cycles of escalated BEACOPP are administered, and then PET is performed for the guidance of further treatment: two further cycles of escalated BEACOPP are recommended if the PET is negative and four further cycles if it is positive, followed by radiotherapy of PET- positive residual tumor tissue. The five-year survival of patients with Hodgkin lymphoma is 95%. In case of disease recurrence, high-dose chemotherapy followed by autologous stem-cell transplantation is performed, and targeted drugs including brentuxi- mab vedotin, nivolumab, and pembrolizuab are used.
CONCLUSION
The highly favorable long-term prognosis of HL necessitates careful consideration of the intensity of treatment as well as thorough follow-up to enable the detection of late sequelae, such as second tumors or organ damage.
Topics: Adult; Drug Therapy; Guidelines as Topic; Hodgkin Disease; Humans; Neoplasm Staging; Prognosis; Radiotherapy
PubMed: 30149835
DOI: 10.3238/arztebl.2018.0535 -
Lupus May 2022Belimumab is the first biological agent approved for the treatment of systemic lupus erythematosus (SLE). The efficacy and safety of belimumab for SLE patients are not... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Belimumab is the first biological agent approved for the treatment of systemic lupus erythematosus (SLE). The efficacy and safety of belimumab for SLE patients are not clear. Therefore, this meta-analysis is integrating the efficacy and safety of belimumab for patients with SLE.
METHODS
PubMed, EMBASE, and Cochrane Library were searched for randomized clinical trials (RCTs) that studied the efficacy and safety of belimumab plus standard therapy before November 1, 2021. Data were pooled using the random-effects model and are expressed as risk ratios (RRs) or mean difference (MD) and corresponding 95% confidence intervals (CIs). Heterogeneity was assessed and quantified using .
RESULTS
Seven RCTs with 3,009 participants were included in this meta-analysis. Belimumab showed significantly decreased at least a 4-point improvement in Safety of Estrogen in Lupus National Assessment (SELENA)-Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score than placebo (RR, 1.32; 95% CI, 1.21-1.44; < 0.001). However, belimumab significantly reduced the prednisone dose by 50% or more than placebo (RR, 1.59; 95% CI, 1.17-2.15; = 0.003) and belimumab significantly increased the 36 Physical Component Summary (PCS) score (MD, 1.60; 95% CI, 0.30-2.90; = 0.02). Regarding adverse events, there was no significant difference between the belimumab group and the control group.
CONCLUSION
The results suggest that belimumab plus standard therapy is more effective than placebo plus standard therapy in SLE patients.
Topics: Antibodies, Monoclonal, Humanized; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Odds Ratio; Treatment Outcome
PubMed: 35321609
DOI: 10.1177/09612033221090888