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Angiogenesis Inhibitors for the Treatment of Ovarian Cancer: An Updated Systematic Review and Meta-analysis of Randomized Controlled Trials.

ABSTRACT: BACKGROUND:Angiogenesis inhibitors showed activity in ovarian cancer, but preliminary data could not accurately reflect the survival benefit. We thus did a systematic review and meta-analysis of randomized controlled trials to reassess the efficacy and safety of angiogenesis inhibitors combined with chemotherapy for ovarian cancer. METHODS:We searched PubMed, EMBASE, Cochrane, and ClinicalTrials.gov for randomized controlled trials comparing angiogenesis inhibitors containing therapy with conventional chemotherapy alone or no further treatment. Our main outcomes were the progression-free survival (PFS), overall survival (OS), and common adverse events. RESULTS:Fifteen trials were included (N = 8721 participants). For newly diagnosed ovarian cancer, combination treatment with angiogenesis inhibitors and chemotherapy yielded a lower risk of disease progression (hazard ratio [HR], 0.83; 95% confidence interval (CI), 0.71-0.97) and no improved OS (HR, 0.95; 95% CI, 0.86-1.05). In the high-risk progression subgroup, the addition of bevacizumab significantly improved PFS (HR, 0.72; 95% CI, 0.65-0.81) and OS (HR, 0.84; 95%CI, 0.74-0.96). In recurrent patients, the combined HR was 0.58 (95% CI, 0.52-0.65) for PFS, and for OS, the combined HR was 0.86 (95% CI, 0.79-0.94). We found no significant improvement for either PFS (HR, 0.80; 95% CI, 0.63-1.01) or OS (HR, 1.06; 95% CI, 0.88-1.28) in the pure maintenance therapy.In the overall population, angiogenesis inhibitors increased the incidence of gastrointestinal perforation (risk ratio [RR], 2.57; 95% CI, 1.66-3.97), hypertension (RR, 7.60; 95% CI, 2.79-20.70), arterial thromboembolism (RR, 2.27; 95% CI, 1.34-3.84), proteinuria (RR, 4.31; 95% CI, 2.15-8.64), and complication of wound healing (RR, 1.72, 95% CI, 1.12-2.63). CONCLUSIONS:Combination treatment with angiogenesis inhibitors and chemotherapy significantly improved PFS and OS in both patients with high-risk of progression and recurrent ovarian cancer, with an increased incidence of common adverse events. Conversely, we detected no statistically significant survival benefit in the pure maintenance setting. The main limitation of the review is clinical heterogeneity across the studies.

SUBMITTER: Wang H

PROVIDER: S-EPMC5976222 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Angiogenesis Inhibitors for the Treatment of Ovarian Cancer: An Updated Systematic Review and Meta-analysis of Randomized Controlled Trials.

Wang Haihong H Xu Tie T Zheng Lifen L Li Guiling G

International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 20180601 5

<h4>Background</h4>Angiogenesis inhibitors showed activity in ovarian cancer, but preliminary data could not accurately reflect the survival benefit. We thus did a systematic review and meta-analysis of randomized controlled trials to reassess the efficacy and safety of angiogenesis inhibitors combined with chemotherapy for ovarian cancer.<h4>Methods</h4>We searched PubMed, EMBASE, Cochrane, and ClinicalTrials.gov for randomized controlled trials comparing angiogenesis inhibitors containing ther ...[more]

PMID: 29561301

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Project description:Antiangiogenesis therapy has been demonstrated to prolong the free survival with tolerable toxicity. However the efficacy of these drugs in overall survival (OS) remains controversial. This study was designed to assess the overall performance of antiangiogenesis therapy in improving the survival of ovary cancer (OC) patients.Electronic database of PubMed, Embase, MEDLINE, and the Cochrane Central Register of Controlled Trials were searched to identify relevant clinical randomized control trial (RCTs) assessing the therapeutic value of antiangiogenesis therapy in OC patients during 2011 to 2017. Additionally, abstracts of annual meetings were also conducted. Only English articles were considered. Progression free survival (PFS), OS, and objective response rate (ORR) were obtained from eligible RCTs. The HRs for time-to-event variables and ORs for dichotomous outcomes with their 95% CIs were used for this meta-analysis. All the statistical analyses were carried out by Stata 11.0 software using a fixed or random-models according to heterogeneity.A total of 15 RCTs including 9359 patients were recruited into this meta-analysis. Addition of antiangiogenic agents improved PFS (HR?=?0.71, 95% CI 0.62-0.81, P?<?.001), OS (HR?=?0.92, 95% CI 0.86-0.98, P?=?.008) and ORR (OR?=?1.74, 95% CI 1.27-2.39, P?=?.001) compared to placebo or chemotherapy alone in overall analysis. Antiangiogenic agents prolonged both PFS (HR?=?0.58, 95% CI 0.52-0.65, P?=?.000) and OS (HR=0.84, 95% CI 0.76-0.92, P?=?.000) in recurrent settings but only PFS in primary settings (HR?=?0.88, 95% CI 0.79-0.98, P?=?.020), longer PFS and OS in both platinum-sensitive recurrent patients (HR?=?0.56, 95% CI 0.48-0.64, P?=?.000, PFS; HR?=?0.86, 95% CI 0.76-0.98, P?=?.027, OS) as well as platinum-resistant recurrent cases (HR?=?0.54, 95% CI 0.41-0.71, P?=?.000, PFS; HR?=?0.84, 95% CI 0.71-0.98, P?=?.029, OS). Throughout therapy improved PFS (HR?=?0.66, 95% CI 0.57-0.76, P?<?.001) and OS (HR?=?0.89, 95% CI 0.83-0.96, P?=?.001). However the maintenance therapy of antiangiogenic agents was irrelevant to a longer PFS or OS.Based on the available studies, antiangiogenic agents play an important role in the survival of OC patients. More randomized controlled trials are needed to reach more convinced conclusion.

Project description:BackgroundThis study aimed to assess the effectiveness and safety of angiogenesis inhibitors for the treatment of patients with small cell lung cancer (SCLC) via meta-analysis.MethodsElectronic databases including PubMed, Embase, and Cochrane Library were searched to look for eligible studies through February 1, 2016. RCTs comprising angiogenesis inhibitors and nonangiogenesis inhibitors for SCLC patients were investigated. The extracted data including overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) were summarized. In addition, the common adverse events (AEs) were also explored.ResultsThere were 7 phase II/III RCTs, encompassing 1322 SCLC patients eligible for meta-analysis. In comparison to nonangiogenesis inhibitors, angiogenesis inhibitors treatment was not associated with improvement of PFS [HR = 0.87, 95% CI (0.74-1.02), P = 0.09), OS [HR = 0.99, 95% CI (0.88-1.12), P = 0.91], or ORR [OR = 1.12, 95% CI (0.85-1.47), P = 0.41). Also, there was no improvement in 1-year survival rate [OR = 0.96, 95% CI (0.74-1.19), P = 0.63)], 2-year survival rate [OR = 1.00, 95% CI (0.66-1.51), P = 1.00)] or 1-year progression-free survival rates [OR = 0.95, 95% CI (0.69-1.31), P = 0.76)]. However, from subgroup analyses, it was observed that angiogenesis inhibitors improved ORR [HR = 1.66 (95% CI 1.02-2.71), P = 0.04] in phase II studies and bevacizumab improved PFS [HR = 0.73 (95% CI 0.42-0.97), P = 0.04]. It is important to note that angiogenesis inhibitors reduced emesis [OR = 0.38, 95% CI (0.17-0.85), P = 0.02], but increased incidence of constipation [OR = 4.02, 95% CI (2.14-7.55), P < 0.0001) and embolism [OR = 2.24, 95% CI (1.45-3.47), P = 0.0003).ConclusionAdding angiogenesis inhibitors to chemotherapy did not improve PFS, OS, ORR, 1-year survival rate, 2-year survival rate or 1-year progression-free survival rate for SCLC. However, subgroup analysis revealed that bevacizumab enhanced PFS. Angiogenesis inhibitors also had a high incidence of constipation and embolism.

Project description:Aim:The aim of this study was to summarize the characteristics, efficacy, and safety of vesicular monoamine transporter-2 (VMAT-2) inhibitors for treating tardive dyskinesia (TD). Materials and methods:We conducted a literature search in PubMed, Cochrane Database, and ClinicalTrials.gov, screening for systematic reviews, meta-analyses or double-blind, randomized, placebo-controlled trials (DBRPCTs) reporting efficacy or safety data of VMAT-2 inhibitors (tetrabenazine, deutetrabenazine, and valbenazine) in patients with TD. A random effects meta-analysis of efficacy and safety data from DBRPCTs was performed. Results:Two acute, 12-week DBRPCTs with deutetrabenazine 12-48 mg/day (n=413) and 4 acute, 4-6-week double-blind trials with valbenazine 12.5-100 mg/day (n=488) were meta-analyzable, without meta-analyzable, high-quality data for tetrabenazine. Regarding reduction in total Abnormal Involuntary Movement Scale (AIMS) scores (primary outcome), both deutetrabenazine (k=2, n=413, standardized mean difference [SMD] =-0.40, 95% confidence interval [CI] =-0.19, -0.62, p<0.001; weighted mean difference (WMD) =-1.44, 95% CI =-0.67, -2.19, p<0.001) and valbenazine (k=4, n=421, SMD =-0.58, 95% CI =-0.26, -0.91, p<0.001; WMD =-2.07, 95% CI =-1.08, -3.05, p<0.001) significantly outperformed placebo. Results were confirmed regarding responder rates (?50% AIMS total score reduction; deutetrabenazine: risk ratio [RR] =2.13, 95% CI =1.10, 4.12, p=0.024, number-needed-to-treat [NNT] =7, 95% CI =3, 333, p=0.046; valbenazine: RR =3.05, 95% CI =1.81, 5.11, p<0.001, NNT =4, 95% CI =3, 6, p<0.001). Less consistent results emerged from patient-rated global impression-based response (p=0.15) and clinical global impression for deutetrabenazine (p=0.088), and for clinical global impression change for valbenazine (p=0.67). In an open-label extension (OLE) study of deutetrabenazine (?54 weeks) and a dose-blinded valbenazine study (?48 weeks), responder rates increased over time. With valbenazine, discontinuation effects were studied, showing TD symptom recurrence towards baseline severity levels within 4 weeks after valbenazine withdrawal. No increased cumulative or specific adverse (AEs) events versus placebo (acute trials) in extension versus acute trial data were observed. Conclusion:The 2 VMAT-2 inhibitors, valbenazine and deutetrabenazine, are effective in treating TD, both acutely and long-term, without concerns about increased risk of depression or suicide in the TD population. No head-to-head comparison among VMAT-2 inhibitors and no high-quality, meta-analyzable data are available for tetrabenazine in patients with TD.

Project description:In clinical practice guidelines, there is no consensus about the medications that should be initially offered to patients with brucellosis. To provide informative evidence, we compared and ranked brucellosis medications based on their efficacy and safety. For this systematic review and network meta-analysis, we searched 4 English databases and 3 Chinese databases, from the date of database inception to December 13, 2023. We included randomized controlled trials (RCTs) involving children and adolescents with brucellosis, comparing different antibiotic regimens. We excluded studies explicitly targeting patients with spondylitis brucellosis, endocarditis brucellosis, and neuro-brucellosis. The primary outcomes were overall failure (efficacy) and side effects (safety). Secondary outcomes were relapse and therapeutic failure. Pairwise meta-analysis was first examined. Data were analyzed using random effects network meta-analysis, with subgroup and sensitivity analyses performed. The Confidence in Network Meta-Analysis (CINeMA) framework was used to assess the certainty of evidence. The protocol was preregistered in PROSPERO (CRD42023491331). Of the 11,747 records identified through the database search, 43 RCTs were included in the network meta-analysis. Compared with standard therapy (Doxycycline + Rifampicin), Rifampicin + Tetracyclines (RR 4.96; 95% CI 1.47 to 16.70; very low certainty of evidence), Doxycycline + TMP/SMX (RR 0.18; 95% CI 0.06 to 0.52; low certainty of evidence), Doxycycline + Quinolones (RR 0.27; 95% CI 0.11 to 0.71; low certainty of evidence), Streptomycin + Tetracyclines (RR 0.04; 95% CI 0.01 to 0.16; low certainty of evidence), and Single (RR 0.05; 95% CI 0.02 to 0.16; moderate certainty of evidence) were less efficacious. Doxycycline + Gentamicin ranked the best in efficacy (SUCRA values: 0.94), the second is Triple (SUCRA values: 0.87), and the third is Doxycycline + Streptomycin (SUCRA values: 0.78). Brucellosis medications differ in efficacy and safety. Doxycycline + Gentamicin, Triple, and Doxycycline + Streptomycin have superior efficacy and safety. Treatment of brucellosis should strike a balance between efficacy, safety, and cost.

Project description:Osteopathic manipulative treatment (OMT) is a distinctive modality commonly used by osteopathic physicians to complement their conventional treatment of musculoskeletal disorders. Previous reviews and meta-analyses of spinal manipulation for low back pain have not specifically addressed OMT and generally have focused on spinal manipulation as an alternative to conventional treatment. The purpose of this study was to assess the efficacy of OMT as a complementary treatment for low back pain.Computerized bibliographic searches of MEDLINE, EMBASE, MANTIS, OSTMED, and the Cochrane Central Register of Controlled Trials were supplemented with additional database and manual searches of the literature. Six trials, involving eight OMT vs control treatment comparisons, were included because they were randomized controlled trials of OMT that involved blinded assessment of low back pain in ambulatory settings. Data on trial methodology, OMT and control treatments, and low back pain outcomes were abstracted by two independent reviewers. Effect sizes were computed using Cohen's d statistic and meta-analysis results were weighted by the inverse variance of individual comparisons. In addition to the overall meta-analysis, stratified meta-analyses were performed according to control treatment, country where the trial was conducted, and duration of follow-up. Sensitivity analyses were performed for both the overall and stratified meta-analyses.Overall, OMT significantly reduced low back pain (effect size, -0.30; 95% confidence interval, -0.47 - -0.13; P = .001). Stratified analyses demonstrated significant pain reductions in trials of OMT vs active treatment or placebo control and OMT vs no treatment control. There were significant pain reductions with OMT regardless of whether trials were performed in the United Kingdom or the United States. Significant pain reductions were also observed during short-, intermediate-, and long-term follow-up.OMT significantly reduces low back pain. The level of pain reduction is greater than expected from placebo effects alone and persists for at least three months. Additional research is warranted to elucidate mechanistically how OMT exerts its effects, to determine if OMT benefits are long lasting, and to assess the cost-effectiveness of OMT as a complementary treatment for low back pain.

Dataset Information

Angiogenesis Inhibitors for the Treatment of Ovarian Cancer: An Updated Systematic Review and Meta-analysis of Randomized Controlled Trials.

Publications

Angiogenesis Inhibitors for the Treatment of Ovarian Cancer: An Updated Systematic Review and Meta-analysis of Randomized Controlled Trials.

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