scholarly journals Direct Comparisons of Efficacy and Safety Between Actinomycin-D and Methotrexate in Women With Low-Risk Gestational Trophoblastic Neoplasia: A Systematic Review and Meta-Analysis

Author(s):  
Jiatao Hao ◽  
Weihua Zhou ◽  
Mengzhao Zhang ◽  
Hui Yu ◽  
Taohong Zhang ◽  
...  

Abstract Background: Actinomycin-D (Act-D) and Methotrexate (MTX) are both effective first-line agents for low-risk gestational trophoblastic neoplasia (LRGTN) with no consensus regarding which is more effective or less toxic. The primary objective of this meta-analysis is to compare Act-D with MTX in the treatment of LRGTN.Methods: We systematically searched electronic databases, conferences abstracts and trial registries for randomized controlled trials (RCTs) and high-quality non-randamized controlled trials (non-RCTs), comparing Act-D with MTX for patients with LRGTN. Studies were full-text screened for quality assessment and data extraction. Eligible studies must have reported complete remission rate. A fixed-effects meta-analysis was conducted to quantify the efficacy and safety of Act-D and MTX on odds ratios (ORs) and 95% confidence intervals (95%CIs), respectively.Results: A total of 8 RCTs and 9 non-RCTs (1674 patients) were included. In terms of efficacy, Act-D is superior to MTX in complete remission (OR 2.15, 95%CI 1.70 to 2.73). In the stratified analysis, patients from RCTs and non-RCTs both had a better CR from Act-D-based regimen (RCTs: OR 2.17, 95%CI 1.49 to 3.16; non-RCTs: OR 2.14, 95%CI 1.57 to 2.92). In terms of safety, patients receiving Act-D had higher risks of suffering nausea (OR 2.35, 95%CI 1.68 to 3.27), vomiting (OR 2.40, 95%CI 1.63 to 3.54), and alopecia (OR 2.76, 95%CI 1.60 to 4.75). Notably, liver toxicity (OR 0.38, 95%CI 0.19 to 0.76) was the only one that was conformed to have a higher risk for patients receiving MTX. In addition, the pooled results showed no significant difference of anaemia, leucocytopenia, neutropenia, thrombocytopnia, constipation, diarrhea, anorexia, and fatigue between Act-D and MTX.Conclusions: Our meta-analysis suggests that Act-D had better efficacy profile in general, and MTX had less toxicities in LRGTN. Future clinical trials should be better orchestrated to provide more valid data on efficacy and toxicity.

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jiatao Hao ◽  
Weihua Zhou ◽  
Mengzhao Zhang ◽  
Hui Yu ◽  
Taohong Zhang ◽  
...  

Abstract Background Actinomycin-D (Act-D) and Methotrexate (MTX) are both effective first-line agents for low-risk gestational trophoblastic neoplasia (LRGTN) with no consensus regarding which is more effective or less toxic. The primary objective of this meta-analysis is to compare Act-D with MTX in the treatment of LRGTN. Methods We systematically searched electronic databases, conferences abstracts and trial registries for randomized controlled trials (RCTs) and high-quality non-randamized controlled trials (non-RCTs), comparing Act-D with MTX for patients with LRGTN. Studies were full-text screened for quality assessment and data extraction. Eligible studies must have reported complete remission rate. A fixed-effects meta-analysis was conducted to quantify the efficacy and safety of Act-D and MTX on odds ratios (ORs) and 95% confidence intervals (95%CIs), respectively. Results A total of 8 RCTs and 9 non-RCTs (1674 patients) were included. In terms of efficacy, Act-D is superior to MTX in complete remission (80.2% [551/687] vs 65.1% [643/987]; OR 2.15, 95%CI 1.70 to 2.73). In the stratified analysis, patients from RCTs and non-RCTs both had a better complete remission from Act-D-based regimen (RCTs: 81.2% [259/319] vs 66.1% [199/301], OR 2.17, 95%CI 1.49 to 3.16; non-RCTs: 79.3% [292/368] vs 65.0% [444/686], OR 2.14, 95%CI 1.57 to 2.92). In terms of safety, patients receiving Act-D had higher risks of suffering nausea (OR 2.35, 95%CI 1.68 to 3.27), vomiting (OR 2.40, 95%CI 1.63 to 3.54), and alopecia (OR 2.76, 95%CI 1.60 to 4.75). Notably, liver toxicity (OR 0.38, 95%CI 0.19 to 0.76) was the only one that was conformed to have a higher risk for patients receiving MTX. In addition, the pooled results showed no significant difference of anaemia, leucocytopenia, neutropenia, thrombocytopnia, constipation, diarrhea, anorexia, and fatigue between Act-D and MTX. Conclusions Our meta-analysis suggests that Act-D had better efficacy profile in general, and MTX had less toxicities in LRGTN. Future clinical trials should be better orchestrated to provide more valid data on efficacy and toxicity.


2016 ◽  
Vol 26 (5) ◽  
pp. 971-976 ◽  
Author(s):  
Fariba Yarandi ◽  
Azamsadat Mousavi ◽  
Fereshteh Abbaslu ◽  
Soheila Aminimoghaddam ◽  
Sepideh Nekuie ◽  
...  

ObjectivesMethotrexate (MTX) and Actinomycin-D (Act-D) are effective drugs used in the treatment of low-risk gestational trophoblastic neoplasia (LRGTNs). The aim of the present study was to compare intravenous (IV) MTX and IV Act-D in the treatment of LRGTNs.Materials and MethodsSixty-two patients with LRGTN were enrolled in a prospective randomized clinical trial between 2010 and 2013 in Moheb e Yas Hospital, Tehran University of Medical Sciences. Primary treatment regimens were IV MTX, 0.4 mg/kg daily for 5 days every 14 days (25 mg maximum daily dose), and IV Act-D, 1.25 mg/m2 (2 mg maximum dose) every 14 days.ResultsThirty-two and 30 patients were enrolled to MTX and Act-D groups, respectively. Complete remission after receiving first-line chemotherapy was achieved in 79% of all cases, 80% in the Act-D group and 78.1% in the MTX group.Twenty percent of the Act-D patients and 21.9% of the MTX patients showed resistance to the first-line chemotherapy, of which 16.7% and 15.6% responded completely to the second-line monotherapy, respectively. Multiple drug therapy was needed in 3.3% of the Act-D group and 6.3% of the MTX group.We did not find any correlation between treatment response and beta–human chorionic gonadotropin level, uterine mass size, lung metastasis, antecedent pregnancy, and duration from diagnosis to treatment. Adverse effects were not statistically different between the 2 groups.ConclusionsSingle-agent chemotherapy in the treatment of LRGTNs resulted in an overall complete remission rate of 79%, 80% in the Act-D group and 78.1% in MTX group, with no statistically significant difference. Whereas this study represents an important step in comparing single-agent treatments, comparison of other regimens will be required to determine the optimal single-agent therapy.


PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0248524
Author(s):  
Rui Li ◽  
Zhiyong Tang ◽  
Fu Liu ◽  
Ming Yang

Background Pneumocystis pneumonia (PCP) has a significant impact on the mortality of immunocompromised patients. It is not known whether the prophylactic application of trimethoprim-sulfamethoxazole (TMP-SMZ) can reduce the incidence of PCP and mortality in the human immunodeficiency virus (HIV)-negative immunodeficient population. The safety profile is also unknown. There have been few reports on this topic. The aim of this study was to systematically evaluate the efficacy and safety of the use of TMP-SMZ for the prevention of PCP in this population of patients from the perspective of evidence-based medicine. Methods A comprehensive search without restrictions on publication status or other parameters was conducted. Clinical randomized controlled trials (RCTs) or case-control trials (CCSs) of TMP-SMZ used for the prevention of PCP in HIV-negative immunocompromised populations were considered eligible. A meta-analysis was performed using the Mantel-Haenszel fixed-effects model or Mantel-Haenszel random-effects model, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated and reported. Results Of the 2392 records identified, 19 studies (n = 4135 patients) were included. The efficacy analysis results indicated that the PCP incidence was lower in the TMP-SMZ group than in the control group (OR = 0.27, 95% CI (0.10, 0.77), p = 0.01); however, the rate of drug discontinuation was higher in the TMP-SMZ group than in the control group (OR = 14.31, 95% CI (4.78, 42.91), p<0.00001). In addition, there was no statistically significant difference in the rate of mortality between the two groups (OR = 0.54, 95% CI (0.21, 1.37), p = 0.19). The safety analysis results showed that the rate of adverse events (AEs) was higher in the TMP-SMZ group than in the control group (OR = 1.92, 95% CI (1.06, 3.47), p = 0.03). Conclusions TMP-SMZ has a better effect than other drugs or the placebo with regard to preventing PCP in HIV-negative immunocompromised individuals, but it may not necessarily reduce the rate of mortality, the rate of drug discontinuation or AEs. Due to the limitations of the research methodologies used, additional large-scale clinical trials and well-designed research studies are needed to identify more effective therapies for the prevention of PCP.


2017 ◽  
Vol 51 (2) ◽  
Author(s):  
Ranhel C. De Roxas ◽  
Roland Dominic G. Jamora

Introduction. Coenzyme Q10, also known as Ubiquinone, is a substance now being used as a dietary supplement in many countries including the Philippines. It has also been the focus of several researches as treatment for several diseases including Parkinson’s Disease. Several studies have shown that Coenzyme Q10 inhibits mitochondrial dysfunction in Parkinson’s Disease, hence delaying its progression. Objectives. The objective of this study is to assess and summarize the available evidence on the efficacy and safety of Coenzyme Q10 administration in the prevention of the progression of early Parkinson’s Disease. Methods. This is meta-analysis of randomized controlled trials on the use of Coenzyme Q10 in Parkinson’s Disease. A literature search in several databases was conducted for relevant studies. Three randomized controlled trials met the inclusion criteria. The efficacy of Coenzyme Q10 were measured using the total and the component scores of the Unified Parkinson Disease Rating Scale on follow-up. On the other hand, safety were measured using the withdrawal rate and the associated adverse reactions during the therapy of CoQ10. The Review Manager Software was utilized for the meta-analysis. Results. Compared to Placebo, treatment of CoQ10 did not show any significant difference in the mean scores of the UPDRS mental and ADL scores. Interestingly, the UPDRS motor score showed a significant difference between Coenzyme Q10 and placebo, but no significant difference when a subgroup analysis between high-dose (-4.03 [-15.07-7.01], p-value 0.47, I2 67%, P for heterogeneity 0.08) and low-dose Coenzyme Q10 (0.53 [-0.891.94], p-value 0.47, I2 34%, P for heterogeneity 0.22) was done. Overall, there was no significant difference in the total UPDRS score (0.68 [-0.61-1.97], p-value 0.30, I2 0%, P for heterogeneity 0.70). The most common side effects of the use of Coenzyme Q10 are anxiety, back pain, headache, sore throat, nausea, dizziness and constipation. Conclusion. Contrary to some animal and human studies, this meta-analysis showed that the use of CoQ10 results to nonsignificant improvement in all components of the UPDRS scores as opposed to placebo. However, the use of CoQ10 is tolerated and seems to be safe but further studies are needed to validate this finding.


2020 ◽  
Vol 2020 ◽  
pp. 1-16
Author(s):  
Shan-Shan Lin ◽  
Chun-Xiang Liu ◽  
Jun-Hua Zhang ◽  
Hui Wang ◽  
Jing-Bo Zhai ◽  
...  

Objectives. To systematically evaluate the efficacy and safety of sinomenine preparation (SP) for treating ankylosing spondylitis (AS). Methods. Clinical randomized controlled trials (RCTs) of SP for treating AS were systematically identified in six electronic databases including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP), and Wanfang Databases from the inception up to 31 October 2019. Cochrane’s risk of bias tool was used to assess the methodological quality and Review Manager 5.3 software was used to analyze data. Results. A total of 12 RCTs involving 835 patients were finally included. According to interventions, RCTs were divided into two types. The intervention in 10 RCTs was SP combined with conventional pharmacotherapy (CPT) versus CPT and that in 2 RCTs was SP alone versus CPT. The results of the meta-analysis showed that, compared with CPT alone, SP combined with oral CPT has better improvement in BASDAI (WMD = −1.84, 95% CI [−3.31, −0.37], P=0.01), morning stiffness time (WMD = −13.46, 95% CI [−16.12, −10.79], P<0.00001), the Schober test (WMD = 1.26, 95% CI [0.72, 1.80], P<0.00001), the occipital wall test (WMD = −0.55, 95% CI [−0.96, −0.14], P=0.009), the finger-to-ground distance (WMD = −3.28, 95% CI [−5.64, −0.93], P=0.006), 15 m walking time (WMD = −8.81, 95% CI [−13.42, −4.20], P=0.0002), the C-reactive protein (CRP) (WMD = −1.84, 95% CI [−3.24, −0.45], P=0.01), and the total effective rate (RR = 1.10, 95% CI [1.01, 1.20], P=0.03). Besides, it also showed that oral SP alone may be more effective in improving morning stiffness time (WMD = −31.89, 95% CI [−34.91, −28.87], P<0.00001) compared with CPT alone. However, this study cannot provide evidence that loading the injectable SP based on CPT can significantly increase the efficacy due to the insufficient number of studies included. In terms of adverse events, there was no statistically significant difference between the experimental group and the control group. Conclusions. This study shows that oral SP may be effective and safe in the treatment of AS. Due to the low methodological quality of the included RCTs and the limitations of the meta-analysis, it is still necessary to carry out more multicenter, large-sample, and high-quality RCTs to further verify the conclusions. The review protocol was registered on PROSPERO (CRD42018099170), and the review was constructed following the PRISMA guidelines (Annex 1).


2020 ◽  
pp. 204748732093058 ◽  
Author(s):  
Lei Dai ◽  
Yuyue Zuo ◽  
Qiqi You ◽  
Hesong Zeng ◽  
Shiyi Cao

Aim Bempedoic acid is a novel oral drug, which has been increasingly researched to play an important role in the treatment of hypercholesterolemia recently. However, results from original studies were inconsistent and inconclusive. We aimed to conduct a meta-analysis to quantitatively appraise the efficacy and safety of bempedoic acid. Methods PubMed, Embase, Web of Science and Scopus were searched from inception to 30 January 2020. We included randomized controlled trials that compared the efficacy and safety of bempedoic acid with placebo in patients with hypercholesterolemia. Results from trials were presented as mean differences or odds ratios (ORs) with 95% confidence intervals (CIs) and were pooled by random or fixed effects model. The risk of bias and heterogeneity among trials were also assessed and analyzed. Results Pooled analysis of 10 eligible trials showed that bempedoic acid treatment resulted in greater lowering of the low-density lipoprotein cholesterol level than the placebo group (mean difference –23.16%, 95% CI –26.92% to –19.04%). We also found that improvements in lipid parameters and biomarkers were still maintained at weeks 24 and 52 from the long-term trials. As for safety, bempedoic acid did not increase the risk of overall adverse events (OR 1.02, 95% CI 0.88 to 1.18). However, the incidence of adverse events leading to discontinuation was higher in the bempedoic acid group (OR 1.44, 95% CI 1.14 to 1.82). Conclusions Available evidence from randomized controlled trials suggests that bempedoic acid provides a well-tolerated and effective therapeutic option for lipid lowering in patients with hyperlipidemia


2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Ximing Zhang ◽  
Xiumei Tian ◽  
Yuezi Wei ◽  
Hao Deng ◽  
Lichun Ma ◽  
...  

In clinical practice, tegafur, gimeracil, and oteracil potassium (S-1) therapy is commonly administered to treat nasopharyngeal carcinoma (NPC). However, its efficacy and safety remain controversial in both randomized controlled trials (RCTs) and non-RCTs. We aimed to evaluate the efficacy and safety of S-1 treatment for NPC. We searched PubMed, Ovid, EMBASE, the Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, and VIP databases for RCTs of chemotherapy with or without S-1 for NPC, from 2001 to 2020. A meta-analysis was performed using RevMan5.3 and Stata15. Randomized controlled trials published in journals were included irrespective of blinding and language used. Patients were diagnosed with NPC through a clinicopathological examination; patients of all cancer stages and ages were included. Overall, 25 trials and 1858 patients were included. There were significant differences in the complete remission (OR = 2.42, 95% CI (1.88–3.10), P < 0.05 ) and overall response rate (OR = 2.68, 95% CI (2.08–3.45), P < 0.05 ) between the S-1 and non-S-1 groups. However, there was no significant difference in partial remission (OR = 1.10, 95% CI (0.87–1.39), P = 0.42 ) and seven adverse reactions (leukopenia, thrombocytopenia, nausea and vomiting, diarrhea, dermatitis, oral mucositis, and anemia) between the S-1 and non-S-1 groups. Additionally, statistical analyses with six subgroups were performed. S-1 was found to be a satisfactory chemotherapeutic agent combined with radiotherapy, intravenous chemotherapy, or chemoradiotherapy for NPC. As an oral medicine, the adverse reactions of S-1, especially gastrointestinal reactions, can be tolerated by patients, thereby optimizing their quality of life. S-1 may be a better choice for the treatment of NPC. This trial is registered with CRD42019122041.


2019 ◽  
Vol 6 ◽  
pp. 204993611988646
Author(s):  
María Teresa Rosanova ◽  
David Bes ◽  
Pedro Serrano-Aguilar ◽  
Norma Sberna ◽  
Estefania Herrera-Ramos ◽  
...  

Background: The aim of this study was to assess whether daptomycin is safer and more efficacious than comparators for the treatment of serious infection caused by gram-positive microorganisms. Methods: Electronic databases (Medline, EMBASE, the Cochrane Central Register of Controlled Trials and clinical registered trials) were searched to identify randomized controlled trials (RCTs) that assessed the efficacy and safety of daptomycin versus therapy with any other antibiotic comparator. Two reviewers independently applied selection criteria, performed a quality assessment and extracted the data. Heterogeneity was assessed, and a random-effects or fixed-effects model, when appropriate, was used for estimates of risk ratio (RR). The primary outcome assessed was the risk of clinical treatment failure among the intention-to-treat population and the presence of any treatment related adverse event (AEs). Results: A total of seven trials fulfilled the inclusion criteria. Daptomycin treatment failure rates were no different to comparator regimens (RR = 0.96; CI 95% 0.86–1.06). No significantly different treatment related AEs were identified when comparing groups (RR = 0.91; CI 95% 0.83–1.01). Conclusions: No significant differences in treatment failure rates and safety were found using daptomycin or any of the comparators treatment.


2017 ◽  
Vol 31 (1) ◽  
pp. 27-35 ◽  
Author(s):  
Bohai Feng ◽  
Jueting Wu ◽  
Bobei Chen ◽  
Haijie Xiang ◽  
Ruru Chen ◽  
...  

Background Allergic rhinitis (AR) has become a global health problem that constantly affects a large part of the general population, especially children. Objective Sublingual allergen immunotherapy (SLIT) has been used extensively for pediatric AR, although its efficacy and safety are often questioned. In this meta-analysis of randomized controlled trials (RCT), we evaluated the use of SLIT for pediatric AR. Methods A number of medical literature data bases were searched through January 2016 to identify RCTs that examined the use of SLIT for pediatric AR and that assessed clinical outcomes related to efficacy. Descriptive and quantitative information was abstracted. Standardized mean differences (SMD) were calculated by using fixed- and random-effects models. Subgroup analyses were performed. Heterogeneity was assessed by using the I2 metric. A network meta-analysis was used to estimate SMDs between two SLIT protocols for pediatric seasonal AR. All data were extracted from publications or received from the authors. Results Twenty-six studies were eligible for inclusion in the meta-analysis of rhinitis or rhinoconjunctivitis symptom scores, and 19 studies were eligible for the meta-analysis of medication scores. Descriptive and quantitative data were extracted. SLIT differed significantly from placebo in terms of symptom scores (SMD -0.55 [95% confidence interval {CI}, -0.86 to -0.25]; p = 0.0003, I2 = 90%) and medication scores (SMD -0.67 [95% CI, -0.96 to -0.38J; p < 0.00001, I2 = 83%). Oral pruritus was the adverse effect, which occurred most commonly in children who were receiving SLIT. Network meta-analysis revealed no significant difference between the pre-coseasonal and continuous SLIT protocols for seasonal AR in symptom scores (SMD -6.55 [95% CI, -25.38 to 12.29]; p = 0.496) and medication scores (SMD -8.83 [95% CI, -22.10 to 4.43]; p = 0.192). Conclusions Our meta-analysis results indicated that SLIT provided significant symptom relief and reduced the need for medication in pediatric patients Moreover, the safety of SLIT needs to be confirmed in RCTs with larger samples.


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