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Frontiers in Oncology 2024This study aimed to evaluate the relative efficacy and safety of first-line treatment options for metastatic castration-resistant prostate cancer (mCRPC).
OBJECTIVE
This study aimed to evaluate the relative efficacy and safety of first-line treatment options for metastatic castration-resistant prostate cancer (mCRPC).
METHODS
We systematically searched electronic databases, including PubMed and Web of Science, for studies published from their inception to April 3rd, 2023. Inclusion criteria were: 1) Completed Phase III or IV randomized controlled trials (RCTs) registered on ClinicalTrials.gov; 2) Patients with a confirmed diagnosis of mCRPC who had not previously received chemotherapy or novel endocrine therapies. We conducted a network meta-analysis using R software (version 3.4.0). Network graphs and risk of bias graphs were generated using Stata 14.0 and RevMan 5.4, respectively. The primary outcome was overall survival (OS), and the secondary outcome was the incidence of severe adverse events (SAEs).
RESULTS
Seven RCTs encompassing 6,641 patients were included. The network meta-analysis revealed that both docetaxel+prednisone (DP) and cabazitaxel+prednisone (CP) significantly improved OS compared to abiraterone. Compared to placebo, DP showed comparable results to both cabazitaxel 20 mg/m+prednisone (C20P) and cabazitaxel 25 mg/m+prednisone (C25P) in terms of OS. For SAEs, both DP and C20P were superior to C25P, with no statistical difference between C20P and DP. The probability ranking plots indicated that C25P ranked highest for OS, while DP ranked highest for SAEs.
CONCLUSIONS
Based on our network meta-analysis, we recommend cabazitaxel 20 mg/m+prednisone (C20P) as the primary choice for first-line management of mCRPC, followed by DP. Enzalutamide and abiraterone are suggested as subsequent options. Radium-223 may be considered for patients presenting with bone metastases.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD42023443943.
PubMed: 38686197
DOI: 10.3389/fonc.2024.1378993 -
Rheumatology (Oxford, England) Mar 2022SS with childhood onset is a rare autoimmune disease characterized by heterogeneous presentation. The lack of validated classification criteria makes it challenging to...
OBJECTIVES
SS with childhood onset is a rare autoimmune disease characterized by heterogeneous presentation. The lack of validated classification criteria makes it challenging to diagnose. Evidence-based guidelines for treatment of juvenile SS are not available due to the rarity of disease and the paucity of research in this patient population. This systematic review aims to summarize and appraise the current literature focused on pharmacological strategies for management of SS with childhood onset.
METHODS
PubMed and MEDLINE/Scopus databases up to December 2020 were screened for suitable reports highlighting pharmacological treatment of SS with childhood onset using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2009 reporting checklist. Animal studies were excluded.
RESULTS
A total of 43 studies (34 case reports, 8 mini case series and 1 pilot study) were eligible for analysis. The studies retrieved included girls in 88% (120/137) of cases and had very low confidence levels. HCQ was prescribed for parotid swelling, as well as in association with MTX and NSAIDs in patients with arthritis and arthralgia. Corticosteroids such as long courses of oral prednisone and i.v. methylprednisolone were commonly prescribed for children with severe disease presentations. Rituximab was mainly indicated for mucosa-associated lymphoid tissue lymphoma and renal and nervous system complications. Other conventional DMARDs were prescribed in selected cases with extraglandular manifestations.
CONCLUSION
Various therapies are used for the management of juvenile SS and are prescribed based on expert clinician's opinion. There are currently no good-quality studies that allow clinical recommendations for treatment of SS with childhood onset.
Topics: Antirheumatic Agents; Azathioprine; Cyclophosphamide; Cyclosporine; Glucocorticoids; Humans; Hydroxychloroquine; Methotrexate; Rituximab; Sjogren's Syndrome
PubMed: 34289032
DOI: 10.1093/rheumatology/keab579 -
Experimental and Therapeutic Medicine Jan 2021The present study aimed to review relevant, randomized, controlled trials in order to determine the effects of aspirin and heparin treatment on recurrent spontaneous...
The present study aimed to review relevant, randomized, controlled trials in order to determine the effects of aspirin and heparin treatment on recurrent spontaneous abortion (RSA) in women with antiphospholipid syndrome (APS). Previous relevant studies were identified using PubMed, Cochrane, Embase, CNKI, VANFUN and VIP by retrieving appropriate key words. Additionally, key relevant sources in the literature were reviewed and articles published before May 2019 were included. The 22 selected studies included 1,515 patients in the treatment group and 1,531 patients in the control group. These previous studies showed that heparin and aspirin significantly improved live birth rate when compared with treatments using intravenous immunoglobulin, aspirin alone or aspirin combined with prednisone. Moreover, heparin and aspirin greatly increased the birth weight compared with placebo and improved vaginal delivery relative to intravenous immunoglobulin. The gestational age at birth was significantly higher in the heparin and aspirin group compared with the placebo group and the incidence of intrauterine growth restriction was lower in the heparin and aspirin group compared with the placebo group. Furthermore, heparin and aspirin markedly reduced the incidence of miscarriage compared with the aspirin group and the placebo group, and the incidence of pre-eclampsia was lower in the heparin and aspirin group than the placebo group. Thus, heparin and aspirin could be further examined for the treatment of RSA in women with APS.
PubMed: 33365057
DOI: 10.3892/etm.2020.9489 -
Integrative Medicine Research Jun 2022Myasthenia Gravis (MG) is a disorder of neuromuscular transmission bringing mild ocular weakness to severe generalized muscle weakness and disability. The conventional... (Review)
Review
BACKGROUND
Myasthenia Gravis (MG) is a disorder of neuromuscular transmission bringing mild ocular weakness to severe generalized muscle weakness and disability. The conventional treatments have long-term side effects, and Chinese herbal medicines (CHM) have shown possible effect and safety for MG patients, but the existing evidence was not robust enough and the results were out of date.
METHODS
Searching for randomized controlled trials (RCTs) was conducted in 7 databases and clinical trial registries until July 2021. The ROB 2 tool was used to assess the study quality and GRADE was used to assess the quality of whole evidence. Meta-analyses were conducted and the results were presented as risk ratio (RR) or mean difference (MD) with 95% confidence interval (CI).
RESULTS
Nineteen RCTs (1283 participants) testing 13 kinds of CHM with adequate randomization were included and six RCTs investigating Compound Huangqi were included in the meta-analyses. In addition to conventional treatment, nine CHMs reduced symptom scores of MG. Compound Huangqi plus conventional treatment (pyridostigmine bromide or prednisone or both) reduced the symptom scores compared with conventional treatment (MD = -3.56, 95%CI -4.86 to -2.26). Less adverse events happened in the CHM groups (3/247 in the CHM groups, 52/245 in the control groups, RR = 0.13, 95%CI 0.06 to 0.30, 9 RCTs, a total of 492 participants). The effect on quality of life was inconsistent.
CONCLUSION
Nine CHMs could probably bring benefit for MG symptom improvement. Moderate to low certainty of evidence supported Compound Huangqi added-on conventional treatment probably bring extra benefit of improving MG symptoms. Adding CHMs could be safer than giving only conventional treatment.
STUDY REGISTRATION
The protocol was registered in PROSPERO (ID: 32718).
PubMed: 35024335
DOI: 10.1016/j.imr.2021.100806 -
Frontiers in Oncology 2022Interstitial pneumonitis (IP), a potentially fatal complication of non-Hodgkin Lymphoma (NHL) patients received CHOP (cyclophosphamide and doxorubicin and vincristine...
OBJECTIVES
Interstitial pneumonitis (IP), a potentially fatal complication of non-Hodgkin Lymphoma (NHL) patients received CHOP (cyclophosphamide and doxorubicin and vincristine and prednisone)-like chemotherapy, negatively affected patients' clinical outcome and quality of life. We aimed to explore patient-related, disease-related and drug-related risk factors associated with IP and gain a better understanding of the incidence in NHL patients.
METHODS
Databases, including PubMed, Ovid, China National Knowledge Internet (CNKI), and Wanfang Database from inception to January 20, 2022, were searched to identify studies evaluating the risk factors and incidence of IP. The included studies were assessed by Newcastle-Ottawa Quality Scale and above 7 points was considered high quality. The statistical analysis of risk factors was assessed by RevMan software (version 5.3) and incidence of IP was calculated by R software (version 4.1.2). Fixed-or random-effects models were applied to estimated the relative risks (RRs) and 95% confidence interval (Cl).
RESULTS
A total of 12 studies comprised of 3423 NHL patients were included in the analysis. Among the 3 available patient-related risk factors, 6 disease-related risk factors and 3 drug-related risk factors, it was found that only drug-related risk factors were significantly associated with IP development: pegylated liposomes doxorubicin (PLD) replacement (RR = 3.25, 95% CI = 1.69-6.27, 64%), rituximab (RTX) addition (RR = 4.24, 95% CI = 2.58-6.96, 0) and granulocyte colony stimulating factor (G-CSF) administration (RR = 5.80, 95% CI = 3.05-11.05, 0). The pooled incidence of CHOP, R-CHOP, and R-CDOP regimen was 1.0% (95% CI 0.00-0.01, = 8%), 7.0% (95% CI 0.05-0.09, = 64%) and 22.0% (95% CI 0.13-0.32, = 87%) respectively.
CONCLUSION
PLD replacement, RTX addition and G-CSF administration were significant risk factors of IP for NHL patients received the CHOP-like chemotherapy. Clinicians should focus on these patients to detect and treat the IP development timely, which might bring benefit in patients' survival.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO, identifier CRD42022309884.
PubMed: 35720002
DOI: 10.3389/fonc.2022.880144 -
Journal of Geriatric Oncology Nov 2020Several treatment options are available for the management of older adults with newly diagnosed patients with Multiple Myeloma (MM) who are ineligible for hematopoietic... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Several treatment options are available for the management of older adults with newly diagnosed patients with Multiple Myeloma (MM) who are ineligible for hematopoietic cell transplantation (tiMM). We aimed to identify treatment options that provide the best balance in terms of efficacy and safety.
METHODS
We searched bibliographic databases and meeting libraries for search terms reflecting newly diagnosed and older and/or transplant-ineligible patients from inception to October 21, 2018. Phase II/III randomized trials comparing at least two first line treatment regimens for newly diagnosed tiMM were included. We extracted data on efficacy (progression free survival, PFS, overall survival and overall response rate) and safety (grade ¾ toxicities) and conducted network meta-analysis using Bayesian methods and random effects models. Relative ranking of treatment regimens was assessed using Surface under the cumulative ranking (SUCRA) probabilities.
RESULTS
We identified 27 trials involving 12,194 patients. For PFS, the four most effective regimens were: Daratumumab, Bortezomib, Melphalan and Prednisone (SUCRA 0.960) followed by Daratumumab, lenalidomide and dexamethasone (Dara_RD, SUCRA 0.847), Bortezomib, melphalan, prednisone, thalidomide maintenance with bortezomib-thalidomide (SUCRA 0.834) and Bortezomib, Lenalidomide and Dexamethasone (SUCRA 0.739). Among these four most efficacious regimens, toxicity profile was most favorable for Dara_RD (median additional AEs per patient vs dexamethasone = 0.74; 95% CrI 0.51-1.17; SUCRA 0.430).
CONCLUSION
Among first line tiMM regimens, increasing efficacy is associated with increased toxicity. We provide relative ranking of these regimens for both efficacy and safety. Future studies should incorporate geriatric assessments and frailty biomarkers to refine treatment decision-making for each individual patient.
Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bayes Theorem; Humans; Lenalidomide; Multiple Myeloma; Treatment Outcome
PubMed: 32513568
DOI: 10.1016/j.jgo.2020.05.013 -
Frontiers in Pharmacology 2023Metastatic castration-resistant prostate cancer (mCRPC) presents significant treatment selection challenges due to limited therapeutic options. This study aimed to...
Metastatic castration-resistant prostate cancer (mCRPC) presents significant treatment selection challenges due to limited therapeutic options. This study aimed to comprehensively assess the efficacy of multiple treatment regimens for mCRPC through a network meta-analysis (NMA) of randomized controlled trials (RCTs). A systematically comprehensive search for randomized controlled trials (RCTs) was performed in Pubmed, Cochrane Library, Embase, and Web of Science databases. The network meta-analysis was employed to compare the overall survival (OS), progression-free survival (PFS), and radiographic progression-free survival (rPFS) among different interventions at specific time points. This study was prospectively registered with PROSPERO (CRD42023422823). A total of 29 RCTs, involving 12,706 patients and investigating 16 interventions, were included in the analysis. Chempretarget ((capivasertib or cabozantinib) + docetaxel + prednisone)) and PARP (Olaparib or rucaparib) inhibitors emerged as interventions that significantly improved survival outcomes compared to first-line treatment in mCRPC patients. Chempretarget demonstrated superior overall survival starting from the 12th month, while PARP inhibitors showed a clear advantage in progression-free survival within the 3-18 months range. Notably, chempre ((Docetaxel or Cabazitaxel) + prednisone) exhibited favorable performance in radiographic progression-free survival during the 3-18 month period. Our findings underscore the efficacy of chempretarget, PARP inhibitors, and chempre in enhancing survival outcomes for mCRPC patients. Further head-to-head comparisons are warranted to validate these results. These findings carry important implications for treatment decision-making in mCRPC and may guide the development of more effective therapeutic strategies.
PubMed: 38074136
DOI: 10.3389/fphar.2023.1290990 -
The Cochrane Database of Systematic... Mar 2020IgA nephropathy is the most common glomerulonephritis world-wide. IgA nephropathy causes end-stage kidney disease (ESKD) in 15% to 20% of affected patients within 10... (Meta-Analysis)
Meta-Analysis
BACKGROUND
IgA nephropathy is the most common glomerulonephritis world-wide. IgA nephropathy causes end-stage kidney disease (ESKD) in 15% to 20% of affected patients within 10 years and in 30% to 40% of patients within 20 years from the onset of disease. This is an update of a Cochrane review first published in 2003 and updated in 2015.
OBJECTIVES
To determine the benefits and harms of immunosuppression strategies for the treatment of IgA nephropathy.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Register of Studies up to 9 September 2019 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) and quasi-RCTs of treatment for IgA nephropathy in adults and children and that compared immunosuppressive agents with placebo, no treatment, or other immunosuppressive or non-immunosuppressive agents.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed study risk of bias and extracted data. Estimates of treatment effect were summarised using random effects meta-analysis. Treatment effects were expressed as relative risk (RR) and 95% confidence intervals (95% CI) for dichotomous outcomes and mean difference (MD) and 95% CI for continuous outcomes. Risks of bias were assessed using the Cochrane tool. Evidence certainty was evaluated using GRADE methodology.
MAIN RESULTS
Fifty-eight studies involving 3933 randomised participants were included. Six studies involving children were eligible. Disease characteristics (kidney function and level of proteinuria) were heterogeneous across studies. Studies evaluating steroid therapy generally included patients with protein excretion of 1 g/day or more. Risk of bias within the included studies was generally high or unclear for many of the assessed methodological domains. In patients with IgA nephropathy and proteinuria > 1 g/day, steroid therapy given for generally two to four months with a tapering course probably prevents the progression to ESKD compared to placebo or standard care (8 studies; 741 participants: RR 0.39, 95% CI 0.23 to 0.65; moderate certainty evidence). Steroid therapy may induce complete remission (4 studies, 305 participants: RR 1.76, 95% CI 1.03 to 3.01; low certainty evidence), prevent doubling of serum creatinine (SCr) (7 studies, 404 participants: RR 0.43, 95% CI 0.29 to 0.65; low certainty evidence), and may lower urinary protein excretion (10 studies, 705 participants: MD -0.58 g/24 h, 95% CI -0.84 to -0.33;low certainty evidence). Steroid therapy had uncertain effects on glomerular filtration rate (GFR), death, infection and malignancy. The risk of adverse events with steroid therapy was uncertain due to heterogeneity in the type of steroid treatment used and the rarity of events. Cytotoxic agents (azathioprine (AZA) or cyclophosphamide (CPA) alone or with concomitant steroid therapy had uncertain effects on ESKD (7 studies, 463 participants: RR 0.63, 95% CI 0.33 to 1.20; low certainty evidence), complete remission (5 studies; 381 participants: RR 1.47, 95% CI 0.94 to 2.30; very low certainty evidence), GFR (any measure), and protein excretion. Doubling of serum creatinine was not reported. Mycophenolate mofetil (MMF) had uncertain effects on the progression to ESKD, complete remission, doubling of SCr, GFR, protein excretion, infection, and malignancy. Death was not reported. Calcineurin inhibitors compared with placebo or standard care had uncertain effects on complete remission, SCr, GFR, protein excretion, infection, and malignancy. ESKD and death were not reported. Mizoribine administered with renin-angiotensin system inhibitor treatment had uncertain effects on progression to ESKD, complete remission, GFR, protein excretion, infection, and malignancy. Death and SCr were not reported. Leflunomide followed by a tapering course with oral prednisone compared to prednisone had uncertain effects on the progression to ESKD, complete remission, doubling of SCr, GFR, protein excretion, and infection. Death and malignancy were not reported. Effects of other immunosuppressive regimens (including steroid plus non-immunosuppressive agents or mTOR inhibitors) were inconclusive primarily due to insufficient data from the individual studies in low or very low certainty evidence. The effects of treatments on death, malignancy, reduction in GFR at least of 25% and adverse events were very uncertain. Subgroup analyses to determine the impact of specific patient characteristics such as ethnicity or disease severity on treatment effectiveness were not possible.
AUTHORS' CONCLUSIONS
In moderate certainty evidence, corticosteroid therapy probably prevents decline in GFR or doubling of SCr in adults and children with IgA nephropathy and proteinuria. Evidence for treatment effects of immunosuppressive agents on death, infection, and malignancy is generally sparse or low-quality. Steroid therapy has uncertain adverse effects due to a paucity of studies. Available studies are few, small, have high risk of bias and generally do not systematically identify treatment-related harms. Subgroup analyses to identify specific patient characteristics that might predict better response to therapy were not possible due to a lack of studies. There is no evidence that other immunosuppressive agents including CPA, AZA, or MMF improve clinical outcomes in IgA nephropathy.
Topics: Adult; Calcineurin Inhibitors; Cause of Death; Child; Confidence Intervals; Creatinine; Drug Administration Schedule; Drug Therapy, Combination; Glomerular Filtration Rate; Glomerulonephritis, IGA; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Leflunomide; Mycophenolic Acid; Proteinuria; Randomized Controlled Trials as Topic; Remission Induction; Ribonucleosides; Risk; Steroids
PubMed: 32162319
DOI: 10.1002/14651858.CD003965.pub3 -
Cancer Treatment Reviews Feb 2021To evaluate the impact of the hormonal treatment sequencing including abiraterone acetate plus prednisone (AAP) and enzalutamide (ENZ) in mCRPC, and determine which... (Meta-Analysis)
Meta-Analysis
Optimal treatment sequencing of abiraterone acetate plus prednisone and enzalutamide in patients with castration-resistant metastatic prostate cancer: A systematic review and meta-analysis.
PURPOSE
To evaluate the impact of the hormonal treatment sequencing including abiraterone acetate plus prednisone (AAP) and enzalutamide (ENZ) in mCRPC, and determine which sequence provides more benefits for patients.
METHODS
Studies published in English between 1 January 2013 and 30 September 2017 were identified in PubMed and EMBASE electronic databases. Studies assessing the efficacy of treatment sequences, based on AAP and ENZ, in mCRPC patients, were eligible for analysis.
RESULTS
Seventeen studies met the inclusion criteria. Two assessed both treatment sequences AAP → ENZ and ENZ → AAP; it was found that sequence of AAP → ENZ showed a statistically significantly longer PSA-PFS than the observed in ENZ → AAP (pooled HR: 0,54; 95% CI; 0,36-0,82; p < 0,05). The nine studies analysing Doc → AAP → ENZ sequence, revealed favourable results in terms of PFS. The 5 studies which analysed AAP → ENZ sequence, show a decrease in PSA levels ≥ 50% in 11-41% of patients treated with enzalutamide after previous treatment with AAP. In the two studies that analysed the Doc → ENZ → AAP sequence, PSA response rates were much lower than those reported with Doc → AAP → ENZ, with decreases in PSA ≥ 30 of 3-18% and PSA ≥ 50 of 8-11%.
CONCLUSION
Significant clinical efficacy of AAP administered as the first-line treatment in mCRPC patients followed by enzalutamide, delaying disease progression, compared with the ENZ → AAP sequence. However, more studies and randomized trials are needed, to validate the best treatment sequencing.
Topics: Abiraterone Acetate; Antineoplastic Combined Chemotherapy Protocols; Benzamides; Humans; Male; Nitriles; Phenylthiohydantoin; Prednisone; Prostatic Neoplasms, Castration-Resistant; Treatment Outcome
PubMed: 33486302
DOI: 10.1016/j.ctrv.2020.102152 -
The Journal of Rheumatology Dec 2021The epidemiology and treatment of peripheral neuropathy in systemic sclerosis (SSc) is poorly understood. The objectives of this study were to evaluate the incidence,... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The epidemiology and treatment of peripheral neuropathy in systemic sclerosis (SSc) is poorly understood. The objectives of this study were to evaluate the incidence, prevalence, risk factors, and treatments of peripheral neuropathy in SSc.
METHODS
A systematic review of MEDLINE, Embase, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases for literature reporting peripheral neuropathy in SSc was performed. Studies evaluating incidence, prevalence, risk factors, and treatments were synthesized. A metaanalysis using a random effects model was used to evaluate the prevalence of peripheral neuropathy.
RESULTS
This systematic review identified 113 studies that reported 949 of 2143 subjects with at least 1 type of peripheral neuropathy. The mean age was 48.5 years. The mean time between SSc onset and detection of peripheral neuropathy was 8.85 years. The pooled prevalence of neuropathy was 27.37% (95% CI 22.35-32.70). Risk factors for peripheral neuropathy in SSc included advanced diffuse disease, anticentromere antibodies, calcinosis cutis, ischemia of the vasa nervorum, iron deficiency anemia, metoclopramide, pembrolizumab, silicosis, and uremia. There were 73 subjects with successful treatments (n = 36 restoring sensation, n = 37 restoring motor or sensorimotor function). Treatments included decompression surgery, prednisone, cyclophosphamide, carbamazepine, transcutaneous electrical nerve stimulation, tricyclic antidepressants, and intravenous Ig.
CONCLUSION
All-cause peripheral neuropathy is not uncommon in SSc. Compression neuropathies can be treated with decompression surgery. Observational data reporting immunosuppressives and anticonvulsants to treat peripheral neuropathy in SSc are limited and conflicting. Randomized controlled trials are needed to evaluate the efficacy of these interventions.
Topics: Humans; Incidence; Iron Deficiencies; Middle Aged; Peripheral Nervous System Diseases; Risk Factors; Scleroderma, Systemic
PubMed: 34210833
DOI: 10.3899/jrheum.201299