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Medical Science Monitor : International... Dec 2019BACKGROUND This study aimed to conduct a systematic review of the literature to identify key randomized controlled clinical trials (RCTs), followed by network... (Meta-Analysis)
Meta-Analysis
Comparison of Regorafenib, Fruquintinib, and TAS-102 in Previously Treated Patients with Metastatic Colorectal Cancer: A Systematic Review and Network Meta-Analysis of Five Clinical Trials.
BACKGROUND This study aimed to conduct a systematic review of the literature to identify key randomized controlled clinical trials (RCTs), followed by network meta-analysis, to compare the efficacy and safety profiles of regorafenib, fruquintinib, and TAS-102 in previously treated patients with metastatic colorectal carcinoma (mCRC). MATERIAL AND METHODS Systematic literature review was performed using the Medline, Embase, and Cochrane library online databases to identify published randomized controlled trials (RCTs). Hazard ratios (HRs) for progression-free survival (PFS), overall survival (OS), and the odds ratios (ORs) for the objective response rate (ORR), disease control rate (DCR), adverse events (AEs), serious adverse events (SAEs), and fatal adverse events (FAEs) were compared indirectly using network meta-analysis based on a random-effects model. RESULTS Five RCTs that included 2,604 patients fulfilled the eligibility criteria and were analyzed. Indirect comparisons showed that fruquintinib was associated with significant superiority for PFS (HR, 0.57; 95% CI, 0.34-0.95) and DCR (OR, 1.80; 95% CI, 1.08-3.01) when compared with TAS-102 in patients with mCRC. However, there was no significant difference between OS or ORR between regorafenib, fruquintinib, and TAS-102. Fruquintinib was associated with a significantly higher risk of SAEs when compared with TAS-102 or regorafenib. There was no significant difference in the risk of AEs or FAEs following indirect comparison between fruquintinib, regorafenib, and TAS-102. CONCLUSIONS The findings from network meta-analysis showed that fruquintinib was associated with significant superiority for PFS and DCR compared with TAS-102, but fruquintinib was associated with significantly increased risk for SAEs compared with regorafenib and TAS-102.
Topics: Antineoplastic Combined Chemotherapy Protocols; Benzofurans; Colonic Neoplasms; Colorectal Neoplasms; Disease-Free Survival; Drug Combinations; Humans; Network Meta-Analysis; Phenylurea Compounds; Pyridines; Pyrrolidines; Quinazolines; Rectal Neoplasms; Thymine; Trifluridine; Uracil
PubMed: 31790382
DOI: 10.12659/MSM.918411 -
Urology Jun 2024To determine whether neoadjuvant gemcitabine and cisplatin (GC) vs dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (ddMVAC) before radical cystectomy... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To determine whether neoadjuvant gemcitabine and cisplatin (GC) vs dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (ddMVAC) before radical cystectomy improves overall survival (OS), progression-free survival (PFS), and pathologic complete response (pCR) for patients with muscle-invasive bladder cancer with secondary analyses of pathological downstaging and toxicity.
MATERIALS AND METHODS
This systematic review and meta-analysis identified studies of patients with muscle-invasive bladder cancer treated with neoadjuvant GC compared to ddMVAC from PubMed, Web of Science, and EMBASE. Random-effect models for pooled log-transformed hazard ratios (HR) for OS and PFS and pooled odds ratios for pCR and downstaging were developed using the generic inverse variance method and Mantel-Haenszel method, respectively.
RESULTS
Ten studies were identified (4 OS, 2 PFS, and 6 pCR clinical endpoints). Neoadjuvant ddMVAC improved OS (HR 0.71 [95% confidence intervals 0.56; 0.90]), PFS (HR 0.76 [95% confidence intervals 0.60; 0.97]), and pathological downstaging (odds ratio 1.34 [95% confidence interval 1.01; 1.78]) as compared to GC. There was no significant difference between regimens for pCR rates (odds ratio 1.38 [95% confidence interval 0.90; 2.12]). Treatment toxicity was greater with ddMVAC. Limitations result from differences in number of ddMVAC cycles and patient selection between studies.
CONCLUSION
Neoadjuvant ddMVAC is associated with improved OS and PFS vs gemcitabine/cisplatin for patients with muscle-invasive bladder cancer before radical cystectomy. Although rates of pathological complete response were not significantly different, pathological downstaging correlated with OS. ddMVAC should be preferred over gemcitabine/cisplatin for patients with muscle-invasive bladder cancer who can tolerate its greater toxicity.
Topics: Urinary Bladder Neoplasms; Humans; Cisplatin; Neoadjuvant Therapy; Neoplasm Invasiveness; Antineoplastic Combined Chemotherapy Protocols; Gemcitabine; Deoxycytidine; Cystectomy; Doxorubicin; Vinblastine; Methotrexate; Chemotherapy, Adjuvant
PubMed: 38685388
DOI: 10.1016/j.urology.2024.04.034 -
Virology Journal Feb 2024Azvudine has been approved for the treatment of coronavirus disease 2019 (COVID-19) patients in China, and this meta-analysis aims to illustrate the safety of azvudine... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Azvudine has been approved for the treatment of coronavirus disease 2019 (COVID-19) patients in China, and this meta-analysis aims to illustrate the safety of azvudine and its effectiveness in reducing mortality.
METHODS
PubMed, Embase, Web of science, Cochrane Library and the Epistemonikos COVID-19 Living Overview of Evidence database (L.OVE) were searched to aggregate currently published studies. Cochrane risk of bias tool and ROBINS-I tool were used to assess the risk of bias of randomized controlled study and cohort study respectively. Odds radios (ORs) with 95% confidence interval (CIs) were combined for dichotomous variables. Publication bias was assessed by Egger's test and funnel plots.
RESULTS
A total of 184 articles were retrieved from the included databases and 17 studies were included into the final analysis. Pooled analysis showed that azvudine significantly reduced mortality risk in COVID-19 patients compared with controls (OR: 0.41, 95%CI 0.31-0.54, p < 0.001). Besides, either mild to moderate or severe COVID-19 patients could benefit from azvudine administration. There was no significant difference in the incidence of ICU admission (OR: 0.90, 95%CI 0.47-1.72, p = 0.74) and invasive ventilation (OR: 0.94, 95%CI 0.54-1.62, p = 0.82) between azvudine and control group. The incidence of adverse events was similar between azvudine and control (OR: 1.26, 95%CI 0.59-2.70, p = 0.56).
CONCLUSIONS
This meta-analysis suggests that azvudine could reduce the mortality risk of COVID-19 patients, and the safety of administration is acceptable.
TRIAL REGISTRATION
PROSPERO; No.: CRD42023462988; URL: https://www.crd.york.ac.uk/prospero/ .
Topics: Humans; COVID-19; Cohort Studies; China; Databases, Factual; Azides; Deoxycytidine
PubMed: 38395970
DOI: 10.1186/s12985-024-02316-y -
Urology Oct 2020Chemoablation is an emerging treatment for urothelial carcinomas. This review provides an overview of the evidence for intracavitary chemoablation in the treatment of...
Chemoablation is an emerging treatment for urothelial carcinomas. This review provides an overview of the evidence for intracavitary chemoablation in the treatment of urothelial carcinomas. The benefits of such agents include a reduction in morbidity and diseased organ preservation. While numerous agents have shown promise, research is limited due to small patient cohorts, varying follow-up, and no standardized methodology to assess response. Therefore, to date, chemoablation has not been widely adopted. This may change as a novel mitomycin formulation has recently been approved for treating low-grade upper tract urothelial carcinoma. Future studies are ongoing which evaluate other promising chemoablation options in urothelial carcinoma.
Topics: Administration, Intravesical; Antineoplastic Agents; Aziridines; BCG Vaccine; Carcinoma, Transitional Cell; Clinical Trials as Topic; Cystoscopy; Deoxycytidine; Epirubicin; Ethanol; Forecasting; Humans; Indolequinones; Injections, Intralesional; Interferon-alpha; Interleukin-2; Mitomycin; Urinary Bladder Neoplasms; Urothelium; Gemcitabine
PubMed: 32540302
DOI: 10.1016/j.urology.2020.05.066 -
Expert Opinion on Pharmacotherapy May 2020In recent years, different studies regarding psoriatic arthritis (PsA) have shown the pathogenetic role of dysfunction of signaling pathways involving the...
INTRODUCTION
In recent years, different studies regarding psoriatic arthritis (PsA) have shown the pathogenetic role of dysfunction of signaling pathways involving the phosphodiesterase-4 enzyme and transcription factors or enzymes belonging to the kinase (JAK)-signal family pathway. These also represent the target of several drugs known as targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs).
AREAS COVERED
The authors performed a systematic literature search using the PubMed database, as well as through retrieving data from randomized controlled trials, their analysis, and pooled data analysis on the efficacy and safety profile of the PDE4 inhibitor (PDE4i), apremilast, and the inhibitors of JAK (JAKis), tofacitinib, filgotinib, baricitinib, and upadacitinib, in PsA.
EXPERT OPINION
In PsA, the PDE4i, apremilast, and the JAKi, tofacitinib, are effective across multiple clinical domains and have an acceptable tolerability profile, thus expanding the treatment options available for PsA patients. Apremilast and tofacitinib show several advantages mainly represented by their oral administration, a fast onset of action, and a short half-life. Data on tsDMARDs in PsA are still limited, and randomized trials and real-life studies are advocated.
Topics: Administration, Oral; Antirheumatic Agents; Arthritis, Psoriatic; Azetidines; Humans; Janus Kinases; Molecular Targeted Therapy; Phosphodiesterase 4 Inhibitors; Piperidines; Purines; Pyrazoles; Pyrimidines; Pyrroles; Randomized Controlled Trials as Topic; Sulfonamides; Thalidomide; Treatment Outcome
PubMed: 32057269
DOI: 10.1080/14656566.2020.1726317 -
Expert Review of Hematology Oct 2019: The genomic landscape of Waldenström macroglobulinemia (WM) is characterized by recurrent () and mutations (), detected in 90% and 30% of cases, respectively. The...
: The genomic landscape of Waldenström macroglobulinemia (WM) is characterized by recurrent () and mutations (), detected in 90% and 30% of cases, respectively. The role of in clinical features and outcomes to therapy in WM patients is evolving. : We performed a systematic review aimed at evaluating the prevalence of in WM patients, and at assessing differences in clinical features and outcomes to therapy between WM patients with and without . Seventeen studies were included in our analysis. The pooled prevalence of in WM patients was 31%; 34% in and 5% in patients. were associated with higher serum IgM levels and higher risk of hyperviscosity than patients. Very good partial response (VGPR) and progression-free survival (PFS) rates to ibrutinib, with and without rituximab, appeared lower in than in patients. Response and PFS rates were not affected by status on patients treated with proteasome inhibitors. : Our systematic review shows that WM patients with have specific clinical features and have lower response and PFS rates to BTK inhibitors. Our findings support standardization of testing and development of CXCR4-directed therapy.
Topics: Adenine; Agammaglobulinaemia Tyrosine Kinase; Antineoplastic Agents; Blood Viscosity; Gene Expression; Humans; Immunoglobulin M; Mutation; Myeloid Differentiation Factor 88; Piperidines; Progression-Free Survival; Proteasome Inhibitors; Pyrazoles; Pyrimidines; Receptors, CXCR4; Rituximab; Treatment Outcome; Waldenstrom Macroglobulinemia
PubMed: 31343930
DOI: 10.1080/17474086.2019.1649132 -
The Journal of International Medical... Apr 2022To undertake a meta-analysis of the treatment effects of different second-line chemotherapy regimens compared with FOLFIRINOX (FOL [folinic acid], F [fluorouracil], IRIN... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To undertake a meta-analysis of the treatment effects of different second-line chemotherapy regimens compared with FOLFIRINOX (FOL [folinic acid], F [fluorouracil], IRIN [irinotecan], OX [oxaliplatin]) after failure of gemcitabine-based first-line therapy in patients with pancreatic cancer.
METHODS
This meta-analysis searched electronic databases, including Embase®, Medline, PubMed® and the Cochrane library, for eligible studies that reported the use of FOLFIRINOX and other drug regimens as second-line chemotherapy after failure of gemcitabine-based chemotherapy. Pooled analyses for progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR) and grade 3/4 treatment-emergent adverse events (TRAEs) were undertaken.
RESULTS
The analysis included six studies with a total of 858 patients. Compared with the three other second-line regimens, FOLFIRINOX had a significantly longer PFS (hazard ratio [HR] 0.68, 95% confidence interval [CI] 0.52, 0.89) and OS (HR 0.71, 95% CI 0.59, 0.86); and a significantly better ORR (HR 0.43, 95% CI 0.23, 0.80) and DCR (HR 0.71, 95% CI 0.58, 0.88). However, grade 3/4 adverse events were more frequently reported in patients administered FOLFIRINOX compared with the other three regimens.
CONCLUSION
FOLFIRINOX is recommended as a second-line chemotherapy regimen for patients with pancreatic cancer that have failed on gemcitabine-based first-line therapy.Research Registry number: reviewregistry1300.
Topics: Antineoplastic Combined Chemotherapy Protocols; Deoxycytidine; Fluorouracil; Humans; Irinotecan; Leucovorin; Oxaliplatin; Pancreatic Neoplasms; Gemcitabine
PubMed: 35481414
DOI: 10.1177/03000605221093225 -
Expert Review of Hematology May 2020: The traditional therapeutic modalities to manage SR-acute GVHD have focused on the inhibition of the alloreactive T-cell response, while in the setting of SR-chronic...
: The traditional therapeutic modalities to manage SR-acute GVHD have focused on the inhibition of the alloreactive T-cell response, while in the setting of SR-chronic GVHD the focus has been on a combination of T-cell and B-cell targeting strategies. However, new therapeutic modalities have shown promise. The purpose of this review is to summarize the current treatment landscape of SR-acute and chronic GVHD.: A systematic search of MEDLINE, EMBASE, and clinicaltrials.gov databases for published articles, abstracts, and clinical trials pertaining to available therapeutic modalities for SR-acute and SR-chronic GVHD was conducted. Also highlighted is a number of ongoing clinical trials in both SR-acute and SR-chronic GVHD with strategies targeting the JAK-1/2 pathway, the Treg:Tcon ratio, the immunomodulation mediated by mesenchymal stem cells, and the gut microbiome, among others. : Ruxolitinib has emerged as the preferred therapeutic modality for SR-acute GVHD, with alpha-1-antitrypsin and extracorporeal photophoresis (ECP) being reasonable alternatives. Ruxolitinib and Ibrutinib are among the preferred options for SR-chronic GVHD, with ECP being a viable alternative particularly if the skin is involved. A number of novel therapeutic modalities, including those enhancing the activity of regulatory T-cells have shown great promise in early phase trials of SR-chronic GVHD.
Topics: Acute Disease; Adenine; B-Lymphocytes; Chronic Disease; Graft vs Host Disease; Humans; Immunomodulation; Janus Kinase 1; Janus Kinase 2; Nitriles; Photopheresis; Piperidines; Pyrazoles; Pyrimidines; T-Lymphocytes, Regulatory; alpha 1-Antitrypsin
PubMed: 32249631
DOI: 10.1080/17474086.2020.1752175 -
Clinical Drug Investigation Sep 2019Oral nucleoside/nucleotide analogues (NAs) have been advocated for chronic hepatitis B (CHB) treatment with good efficacy. However, less attention has been put on their... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVE
Oral nucleoside/nucleotide analogues (NAs) have been advocated for chronic hepatitis B (CHB) treatment with good efficacy. However, less attention has been put on their adverse events. Therefore, a Bayesian network meta-analysis (NMA) was performed to evaluate the relative safety of five NAs (lamivudine, adefovir dipivoxil, entecavir, telbivudine, and tenofovir disoproxil fumarate) in CHB treatment among adults.
METHODS
Eligible randomized clinical trials (RCTs) and prospective cohort studies were systematically and thoroughly searched until May 1, 2019. Poisson-prior-based Bayesian NMA was performed to synthesize both direct and indirect evidence with reporting hazard ratios (HRs) and 95% credible intervals (CrIs) for serious adverse events (SAEs) and hepatic/renal impairments.
RESULTS
Thirty-three RCTs and 11 prospective cohort studies were identified. As to SAEs, no statistically significant difference was found of any comparison among five NAs. In terms of hepatotoxicity, lamivudine was safer than telbivudine (HR 0.45; 95% CrI 0.21, 0.85), and entecavir increased the risk by 102% (entecavir vs lamivudine: HR 2.02; 95% CrI 1.19, 3.27).
CONCLUSIONS
The findings from this large NMA could influence clinical practice, and the methodological framework of this study could provide evidence-based support to analyze sparse safety data in the field.
Topics: Adenine; Antiviral Agents; Bayes Theorem; Guanine; Hepatitis B, Chronic; Humans; Lamivudine; Network Meta-Analysis; Organophosphonates; Prospective Studies; Telbivudine; Tenofovir
PubMed: 31228017
DOI: 10.1007/s40261-019-00802-8 -
Medicine Dec 2021Recent randomized controlled trials revealed the combination of gemcitabine and capecitabine (GemCap) regime shows promising efficacy in pancreatic cancer patients.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Recent randomized controlled trials revealed the combination of gemcitabine and capecitabine (GemCap) regime shows promising efficacy in pancreatic cancer patients. Here, we conducted a meta-analysis to compare the efficacy and safety of gemcitabine (Gem) with GemCap for pancreatic cancer.
METHODS
The database of MEDLINE (PubMed), EMBASE, Cochrane Central Controster of Controlled Trials, Web of Science was searched for relevant randomized controlled trials before 8 April, 2020. The outcomes were overall survival (OS), 12-month survival rate, progress free survival (PFS), partial response rate (PRR), objective response rate (ORR), and Grade 3/4 toxicities.
RESULTS
Five randomized controlled trials involving 1879 patients were included in this study. The results showed that GemCap significantly improves the OS (hazard ratio = 1.15, 95% CI: 1.037-1.276, P = .008), PFS (hazard ratio = 1.211, 95% CI 1.09-1.344, P = 0), PRR (relative risk (RR) = 0.649, 95% CI 0.488-0.862, P = .003), ORR (RR = 0.605, 95% CI 0.458-0.799, P = 0), and the overall toxicity (RR = 0.708, 95% CI 0.620-0.808, P = .000) compared to Gem alone. However, no significant difference was found in 12-month survival.
CONCLUSIONS
Despite a higher incidence of Grade 3/4 toxicity, GemCap was associated with better outcomes of OS, PFS, PRR, ORR, as compared with Gem, which is likely to become a promising therapy for pancreatic cancer.
Topics: Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Deoxycytidine; Drug Therapy, Combination; Humans; Pancreatic Neoplasms; Randomized Controlled Trials as Topic; Treatment Outcome; Gemcitabine
PubMed: 35049189
DOI: 10.1097/MD.0000000000027870