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Ceftazidime-avibactam: an evidence-based review of its pharmacology and potential use in the treatment of Gram-negative bacterial infections. 头孢他啶-阿维巴坦:其药理学和治疗革兰氏阴性细菌感染的潜在用途的循证综述。
Pub Date : 2014-01-24 eCollection Date: 2014-01-01 DOI: 10.2147/CE.S40698
Philippe Lagacé-Wiens, Andrew Walkty, James A Karlowsky

Avibactam (NXL104, AVE1330A) is a semi-synthetic, non-β-lactam, β-lactamase inhibitor that is active against Ambler class A, class C, and some class D serine β-lactamases. In this review, we summarize the in vitro data, pharmacology, mechanisms of action and resistance, and clinical trial data relating to the use of this agent combined with ceftazidime for the treatment of Gram-negative bacterial infections. The addition of avibactam to ceftazidime improves its in vitro activity against Enterobacteriaceae and Pseudomonas aeruginosa. Avibactam does not improve the activity of ceftazidime against Acinetobacter spp., Burkholderia spp., or most anaerobic Gram-negative rods. Pharmacodynamic data indicate that ceftazidime-avibactam is bactericidal at concentrations achievable in human serum. Animal studies demonstrate that ceftazidime-avibactam is effective in ceftazidime-resistant Gram-negative septicemia, meningitis, pyelonephritis, and pneumonia. Limited clinical trials published to date have reported that ceftazidime-avibactam is as effective as therapy with a carbapenem in complicated urinary tract infection and complicated intra-abdominal infection (combined with metronidazole) including infection caused by cephalosporin-resistant Gram-negative isolates. Safety and tolerability of ceftazidime-avibactam in clinical trials has been excellent, with few serious drug-related adverse events reported. Given the abundant clinical experience with ceftazidime and the significant improvement that avibactam provides in its activity against contemporary β-lactamase-producing Gram-negative pathogens, it is likely this new combination agent will play a role in the empiric treatment of complicated urinary tract infections (monotherapy) and complicated intra-abdominal infections (in combination with metronidazole) caused or suspected to be caused by antimicrobial-resistant pathogens (eg, extended spectrum beta-lactamase-, AmpC-, or Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae and multidrug-resistant P. aeruginosa). Potential future uses also include hospital-acquired pneumonia (in combination with antistaphylococcal and antipneumococcal agents) or treatment of skin and soft tissue infections caused by antimicrobial-resistant Gram-negative pathogens (eg, diabetic foot infections), but further clinical trials are required.

Avibactam (NXL104, AVE1330A)是一种半合成,非β-内酰胺,β-内酰胺酶抑制剂,对Ambler a类,C类和一些D类丝氨酸β-内酰胺酶有活性。本文就该药联合头孢他啶治疗革兰氏阴性菌感染的体外实验数据、药理学、作用机制、耐药及临床试验数据进行综述。在头孢他啶中加入阿维巴坦可提高头孢他啶对肠杆菌科细菌和铜绿假单胞菌的体外活性。阿维巴坦不能提高头孢他啶对不动杆菌、伯克霍尔德氏杆菌或大多数厌氧革兰氏阴性棒的活性。药效学数据表明,头孢他啶-阿维巴坦在人血清中可达到的浓度下具有杀菌作用。动物研究表明,头孢他啶-阿维巴坦对头孢他啶耐药的革兰氏阴性败血症、脑膜炎、肾盂肾炎和肺炎有效。迄今为止发表的有限临床试验报道,头孢他啶-阿维巴坦与碳青霉烯类药物治疗复杂的尿路感染和复杂的腹腔感染(与甲硝唑联合)一样有效,包括由耐头孢菌素革兰氏阴性分离株引起的感染。头孢他啶-阿维巴坦在临床试验中的安全性和耐受性非常好,很少有严重的药物相关不良事件报道。鉴于头孢他啶丰富的临床经验和阿维巴坦对当代产生β-内酰胺酶的革兰氏阴性病原体的活性的显著改善,这种新的联合药物很可能在经典性治疗由或怀疑由耐药病原体引起的复杂尿路感染(单一疗法)和复杂腹腔感染(与甲硝唑联合)中发挥作用。广谱β -内酰胺酶,AmpC-或产碳青霉烯酶的肺炎克雷伯菌肠杆菌科和耐多药铜绿假单胞菌)。潜在的未来用途还包括医院获得性肺炎(与抗葡萄球菌和抗肺炎球菌药物联合使用)或治疗由耐药革兰氏阴性病原体引起的皮肤和软组织感染(例如糖尿病足感染),但需要进一步的临床试验。
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引用次数: 144
Targeted therapy in triple-negative metastatic breast cancer: a systematic review and meta-analysis. 靶向治疗三阴性转移性乳腺癌:系统回顾和荟萃分析。
Pub Date : 2014-01-06 eCollection Date: 2014-01-01 DOI: 10.2147/CE.S52197
Otávio Clark, Tobias Engel Ayer Botrel, Luciano Paladini, Mariana Bhering Andrade Ferreira

Objective: To perform a systematic review and meta-analysis of randomized controlled trials that compared the efficacy of targeted therapy to conventional chemotherapy (CT) in patients with metastatic triple-negative breast cancer (TNBC).

Methods: Several databases were searched, including Medline, Embase, LILACS, and CENTRAL. The primary end point was progression-free survival (PFS). We performed a meta-analysis of the published data. The results are expressed as hazard ratio (HR) or risk ratio, with their corresponding 95% confidence intervals (95% CIs).

Results: The final analysis included twelve trials comprising 2,054 patients with TNBC, which compared conventional CT alone against CT combined with targeted therapy (bevacizumab [Bev], sorafenib [Sor], cetuximab, lapatinib, and iniparib). PFS was superior in previously untreated patients with TNBC who received Bev plus CT compared to CT alone (fixed effect, HR 0.62, 95% CI 0.51-0.75; P<0.00001). Also, PFS was higher in one study that tested Bev plus CT combination in previously treated patients (HR 0.49, 95% CI 0.33-0.74; P=0.0006). Sor plus CT was also tested as first-line and second-line treatments. The pooled data of PFS favored the combination CT plus Sor (fixed effect, HR 0.69, 95% CI 0.49-0.98; P=0.04). Comparisons of iniparib plus CT also had a better PFS than CT alone (fixed effect, HR 0.75, 95% CI 0.62-0.90; P=0.002).

Conclusion: Targeted therapy, when associated with conventional CT, demonstrated gains in the PFS of patients with TNBC.

目的:对转移性三阴性乳腺癌(TNBC)患者进行靶向治疗与常规化疗(CT)疗效比较的随机对照试验进行系统回顾和荟萃分析。方法:检索Medline、Embase、LILACS、CENTRAL等数据库。主要终点为无进展生存期(PFS)。我们对发表的数据进行了荟萃分析。结果用风险比(HR)或风险比表示,并给出相应的95%置信区间(95% ci)。结果:最终分析包括12项试验,包括2054例TNBC患者,比较了常规CT单独与CT联合靶向治疗(贝伐单抗[Bev],索拉非尼[Sor],西妥昔单抗,拉帕替尼和伊尼帕里)。未经治疗的TNBC患者接受Bev + CT治疗的PFS优于单独接受CT治疗(固定效应,HR 0.62, 95% CI 0.51-0.75;结论:当与常规CT相结合时,靶向治疗显示了TNBC患者PFS的增加。
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引用次数: 37
Ibrutinib: an evidence-based review of its potential in the treatment of advanced chronic lymphocytic leukemia. 依鲁替尼:循证评价其治疗晚期慢性淋巴细胞白血病的潜力。
Pub Date : 2013-01-01 Epub Date: 2013-05-16 DOI: 10.2147/CE.S34068
Julio C Chavez, Eva Sahakian, Javier Pinilla-Ibarz

Chronic lymphocytic leukemia (CLL) is a heterogeneous disease with a variable course, and remains an incurable disease. Frequent relapses and eventual resistance to fludarabine characterize symptomatic CLL and portends a dismal prognosis for patients. Growing evidence has shown that signaling pathways such as the B cell receptor and NFkB are implicated in the survival and proliferation of the CLL cells which are ultimately associated with persistence of the disease. The Bruton's tyrosine kinase pathway regulates downstream activation of the B cell receptor and has emerged as an attractive target. Ibrutinib inhibits the Bruton's tyrosine kinase pathway, and consequently induces apoptosis of B cells. Phase I and II studies have shown impressive response rates with an excellent safety profile in patients with refractory/relapsed CLL and elderly treatment-naïve CLL patients. This paper reviews the preclinical and clinical data for ibrutinib when used in the treatment of CLL. Recent studies showing the benefit of combination therapy using ibrutinib, monoclonal antibodies, and chemoimmunotherapy are also discussed.

慢性淋巴细胞白血病(CLL)是一种病程多变的异质性疾病,至今仍是一种不治之症。频繁复发和最终对氟达拉滨耐药是有症状的CLL的特征,预示着患者预后不佳。越来越多的证据表明,B细胞受体和NFkB等信号通路与CLL细胞的存活和增殖有关,最终与疾病的持续存在有关。布鲁顿酪氨酸激酶途径调节B细胞受体的下游激活,并已成为一个有吸引力的目标。依鲁替尼抑制布鲁顿酪氨酸激酶途径,从而诱导B细胞凋亡。在难治性/复发性CLL患者和老年treatment-naïve CLL患者中,I期和II期研究显示出令人印象深刻的反应率和出色的安全性。本文综述了依鲁替尼治疗慢性淋巴细胞白血病的临床前和临床数据。最近的研究显示伊鲁替尼、单克隆抗体和化学免疫治疗联合治疗的益处也进行了讨论。
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引用次数: 22
Lixivaptan - an evidence-based review of its clinical potential in the treatment of hyponatremia. 利西瓦坦——对其治疗低钠血症临床潜力的循证评价
Pub Date : 2013-01-01 Epub Date: 2013-07-11 DOI: 10.2147/CE.S36744
Brendan T Bowman, Mitchell H Rosner

Hyponatremia is the most common electrolyte abnormality seen in clinical practice. Most cases of euvolemic or hypervolemic hyponatremia involve arginine vasopressin (AVP). AVP leads to a concentrated urine and negative free water clearance. Given this primary role of AVP, antagonizing its effect through blockade of its receptor in the distal tubule is an attractive therapeutic target. Lixivaptan is a newer, non-peptide, vasopressin type 2 receptor antagonist. Recent studies have demonstrated efficacy. This review summarizes the clinical pharmacology and data for this new agent.

低钠血症是临床上最常见的电解质异常。大多数高容量或高容量低钠血症病例都涉及精氨酸加压素(AVP)。AVP导致尿液浓缩和游离水清除率为阴性。鉴于AVP的主要作用,通过阻断其在远端小管中的受体来拮抗其作用是一个有吸引力的治疗靶点。利西伐普坦是一种新型的、非肽的血管加压素2型受体拮抗剂。最近的研究已经证明了疗效。本文综述了这种新制剂的临床药理学和数据。
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引用次数: 16
Enzalutamide: an evidence-based review of its use in the treatment of prostate cancer. 恩杂鲁胺:对其用于治疗前列腺癌的循证评价。
Pub Date : 2013-01-01 Epub Date: 2013-04-04 DOI: 10.2147/CE.S34747
Ali R Golshayan, Emmanuel S Antonarakis

Introduction: Enzalutamide is an oral androgen receptor (AR) signaling inhibitor that was specifically engineered to overcome castration-resistant prostate cancer (CRPC) harboring AR amplification or overexpression. Enzalutamide has demonstrated significant activity in men with metastatic CRPC.

Aims: To update the evidence and provide an overview of the available data on enzalutamide.

Evidence review: Peer reviewed articles published and listed in Medline Search were reviewed. In addition, relevant ASCO and ESMO abstracts were searched. The activity of enzalutamide is mediated by potently antagonizing the full-length AR, impairing translocation of the AR from the cytoplasm into the nucleus, and inhibiting the transcriptional activity of the AR by modulating the interaction of the AR with androgen-response elements in gene promoter regions. Enzalutamide has a favorable safety profile and the most common adverse events include fatigue, hot flashes and headache; 1% of patients experienced seizure.

Place in therapy: The AFFIRM phase III study evaluated the clinical utility of treatment with enzalutamide in men with docetaxel-refractory metastatic CRPC. Enzalutamide improved overall survival compared to placebo, with a median overall survival of 18.4 months versus 13.6 months respectively.

Conclusion: Enzalutamide has demonstrated impressive efficacy in men with metastatic CRPC, moving swiftly from a phase I/II study to two pivotal phase III trials testing this agent in both chemotherapy-pretreated as well as chemotherapy-naïve CRPC patients. Ongoing studies are aiming to explore the utility of enzalutamide in earlier stages of the disease, and to investigate the optimal sequencing and combination of enzalutamide with other standard and novel therapies for prostate cancer.

Enzalutamide是一种口服雄激素受体(AR)信号抑制剂,专门用于克服具有AR扩增或过表达的去势抵抗性前列腺癌(CRPC)。恩杂鲁胺在男性转移性CRPC中显示出显著的活性。目的:更新关于恩杂鲁胺的证据并概述现有数据。证据审查:对Medline Search中发表的同行评议文章进行审查。此外,检索了相关的ASCO和ESMO摘要。enzalutamide的活性是通过有效拮抗全长AR、抑制AR从细胞质向细胞核的易位以及通过调节AR与基因启动子区域雄激素反应元件的相互作用来抑制AR的转录活性而介导的。恩杂鲁胺具有良好的安全性,最常见的不良事件包括疲劳、潮热和头痛;1%的患者出现癫痫发作。应用于治疗:AFFIRM III期研究评估了enzalutamide治疗多西他赛难治性转移性CRPC的临床疗效。与安慰剂相比,Enzalutamide改善了总生存期,中位总生存期分别为18.4个月和13.6个月。结论:Enzalutamide在男性转移性CRPC患者中显示出令人印象深刻的疗效,从I/II期研究迅速进入两个关键的III期试验,在化疗预处理和chemotherapy-naïve CRPC患者中测试该药物。正在进行的研究旨在探索enzalutamide在疾病早期阶段的效用,并研究enzalutamide与其他标准和新型前列腺癌治疗的最佳测序和组合。
{"title":"Enzalutamide: an evidence-based review of its use in the treatment of prostate cancer.","authors":"Ali R Golshayan,&nbsp;Emmanuel S Antonarakis","doi":"10.2147/CE.S34747","DOIUrl":"https://doi.org/10.2147/CE.S34747","url":null,"abstract":"<p><strong>Introduction: </strong>Enzalutamide is an oral androgen receptor (AR) signaling inhibitor that was specifically engineered to overcome castration-resistant prostate cancer (CRPC) harboring AR amplification or overexpression. Enzalutamide has demonstrated significant activity in men with metastatic CRPC.</p><p><strong>Aims: </strong>To update the evidence and provide an overview of the available data on enzalutamide.</p><p><strong>Evidence review: </strong>Peer reviewed articles published and listed in Medline Search were reviewed. In addition, relevant ASCO and ESMO abstracts were searched. The activity of enzalutamide is mediated by potently antagonizing the full-length AR, impairing translocation of the AR from the cytoplasm into the nucleus, and inhibiting the transcriptional activity of the AR by modulating the interaction of the AR with androgen-response elements in gene promoter regions. Enzalutamide has a favorable safety profile and the most common adverse events include fatigue, hot flashes and headache; 1% of patients experienced seizure.</p><p><strong>Place in therapy: </strong>The AFFIRM phase III study evaluated the clinical utility of treatment with enzalutamide in men with docetaxel-refractory metastatic CRPC. Enzalutamide improved overall survival compared to placebo, with a median overall survival of 18.4 months versus 13.6 months respectively.</p><p><strong>Conclusion: </strong>Enzalutamide has demonstrated impressive efficacy in men with metastatic CRPC, moving swiftly from a phase I/II study to two pivotal phase III trials testing this agent in both chemotherapy-pretreated as well as chemotherapy-naïve CRPC patients. Ongoing studies are aiming to explore the utility of enzalutamide in earlier stages of the disease, and to investigate the optimal sequencing and combination of enzalutamide with other standard and novel therapies for prostate cancer.</p>","PeriodicalId":10764,"journal":{"name":"Core Evidence","volume":"8 ","pages":"27-35"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CE.S34747","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31361419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 30
Lapatinib plus chemotherapy or endocrine therapy (CET) versus CET alone in the treatment of HER-2-overexpressing locally advanced or metastatic breast cancer: systematic review and meta-analysis. 拉帕替尼联合化疗或内分泌治疗(CET)与单独化疗治疗her -2过表达的局部晚期或转移性乳腺癌:系统评价和荟萃分析
Pub Date : 2013-01-01 Epub Date: 2013-09-30 DOI: 10.2147/CE.S50474
Tobias Engel Ayer Botrel, Luciano Paladini, Otávio Augusto C Clark

Background: This paper reports a systematic review and meta-analysis of all randomized controlled trials comparing the efficacy of lapatinib plus chemotherapy or endocrine therapy (CET) versus CET alone in human epidermal growth factor receptor 2-overexpressing (HER-2+) locally advanced or metastatic breast cancer.

Methods: Several databases were searched, including MEDLINE, EMBASE, LILACS, and CENTRAL. The primary endpoints were progression-free survival and overall survival. The side effects of each treatment were analyzed. The data extracted from the studies were combined by using the hazard ratio or risk ratio with their corresponding 95% confidence interval (CI).

Results: A total of 113 references were identified and screened. The final analysis included four trials comprising 1,073 patients with HER-2+. The overall response rate was higher in patients who received the combination of CET plus lapatinib (risk ratio 0.78; 95% CI 0.71-0.85; P < 0.00001) but with significant heterogeneity (χ(2) = 15.61, df = 3; P = 0.001; I(2) = 81%). This result remained favorable to the use of lapatinib when a random-effects model analysis was performed (risk ratio 0.76; 95% CI 0.62-0.94; P = 0.01). Progression-free survival was also higher in patients who received CET plus lapatinib (hazard ratio 0.57; 95% CI 0.49-0.66; P < 0.00001) with no heterogeneity detected on this analysis (χ(2) = 3.05; df = 3; P = 0.38; I(2) = 1%). Overall survival was significantly longer in patients who received CET plus lapatinib (hazard ratio 0.80; 95% CI 0.69-0.92; P = 0.002) without heterogeneity on this analysis (χ(2) = 1.26; df = 3; P = 0.74; I(2) = 0%). Regarding adverse events and severe toxicities (grade ≥3), the group receiving CET plus lapatinib had higher rates of neutropenia (risk ratio 2.08; 95% CI 1.64-2.62; P < 0.00001), diarrhea (risk ratio 4.82; 95% CI 3.14-7.41; P < 0.00001), and rash (risk ratio 8.03; 95% CI 2.46-26.23; P = 0.0006).

Conclusion: The combination of CET plus lapatinib increased the overall response rate, progression-free survival, and overall survival in patients with HER-2+ locally advanced or metastatic breast cancer.

背景:本文报道了一项系统回顾和荟萃分析,比较了拉帕替尼联合化疗或内分泌治疗(CET)与单独使用CET治疗人表皮生长因子受体2过表达(HER-2+)局部晚期或转移性乳腺癌的疗效。方法:检索MEDLINE、EMBASE、LILACS、CENTRAL等数据库。主要终点为无进展生存期和总生存期。分析各治疗方法的副作用。从研究中提取的数据通过使用风险比或风险比及其相应的95%置信区间(CI)进行合并。结果:共筛选文献113篇。最终的分析包括四项试验,包括1073名HER-2+患者。接受CET +拉帕替尼联合治疗的患者总体缓解率更高(风险比0.78;95% ci 0.71-0.85;P < 0.00001),但异质性显著(χ(2) = 15.61, df = 3;P = 0.001;I(2) = 81%)。当进行随机效应模型分析时,这一结果仍然有利于拉帕替尼的使用(风险比0.76;95% ci 0.62-0.94;P = 0.01)。接受CET +拉帕替尼治疗的患者无进展生存率也更高(风险比0.57;95% ci 0.49-0.66;P < 0.00001),本分析未发现异质性(χ(2) = 3.05;Df = 3;P = 0.38;I(2) = 1%)。接受CET +拉帕替尼治疗的患者总生存期明显延长(风险比0.80;95% ci 0.69-0.92;P = 0.002),本分析无异质性(χ(2) = 1.26;Df = 3;P = 0.74;I(2) = 0%)。在不良事件和严重毒性(≥3级)方面,接受CET +拉帕替尼组中性粒细胞减少率较高(风险比2.08;95% ci 1.64-2.62;P < 0.00001)、腹泻(风险比4.82;95% ci 3.14-7.41;P < 0.00001),皮疹(风险比8.03;95% ci 2.46-26.23;P = 0.0006)。结论:CET联合拉帕替尼可提高HER-2+局部晚期或转移性乳腺癌患者的总缓解率、无进展生存期和总生存期。
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引用次数: 14
An evidence-based review of obatoclax mesylate in the treatment of hematological malignancies. 甲磺酸奥巴曲克治疗血液恶性肿瘤的循证综述。
Pub Date : 2013-01-01 Epub Date: 2013-03-14 DOI: 10.2147/CE.S42568
Carolyn A Goard, Aaron D Schimmer

Obatoclax mesylate is an intravenously-administered drug under investigation in Phase I and II clinical trials as a novel anticancer therapeutic for hematological malignancies and solid tumors. Obatoclax was developed as a pan-inhibitor of antiapoptotic members of the B cell chronic lymphocytic leukemia/lymphoma 2 (BCL-2) family of proteins, which control the intrinsic or mitochondrial pathway of apoptosis. Resistance to apoptosis through dysregulation of BCL-2 family members is commonly observed in hematological malignancies, and can be linked to therapeutic resistance and poor clinical outcomes. By inhibiting pro-survival BCL-2 family proteins, including MCL-1, obatoclax is proposed to (1) trigger cell death as a single agent, and (2) potentiate the anticancer effects of other therapeutics. Preclinical investigations have supported these proposals and have provided evidence suggestive of a promising therapeutic index for this drug. Phase I trials of obatoclax mesylate in leukemia and lymphoma have defined well-tolerated regimens and have identified transient neurotoxicity as the most common adverse effect of this drug. In these studies, a limited number of objective responses were observed, along with hematological improvement in a larger proportion of treated patients. Published Phase II evaluations in lymphoma and myelofibrosis, however, have not reported robust single-agent activity. Emerging evidence from ongoing preclinical and clinical investigations suggests that the full potential of obatoclax mesylate as a novel anticancer agent may be realized (1) in rational combination treatments, and (2) when guided by molecular predictors of therapeutic response. By understanding the molecular underpinnings of obatoclax response, along with optimal therapeutic regimens and indications, the potential of obatoclax mesylate for the treatment of hematological malignancies may be further clarified.

甲磺酸 Obatoclax 是一种静脉注射药物,作为一种治疗血液恶性肿瘤和实体瘤的新型抗癌疗法,目前正在进行 I 期和 II 期临床试验。Obatoclax 是作为 B 细胞慢性淋巴细胞白血病/淋巴瘤 2(BCL-2)家族蛋白的抗凋亡泛抑制剂而开发的,这些蛋白控制着细胞凋亡的内在或线粒体途径。在血液恶性肿瘤中经常可以观察到通过 BCL-2 家族成员失调而导致的凋亡抵抗,这可能与治疗抵抗和临床疗效不佳有关。通过抑制包括 MCL-1 在内的促生存 BCL-2 家族蛋白,obatoclax 可(1)作为单药引发细胞死亡,(2)增强其他疗法的抗癌效果。临床前研究支持这些建议,并提供证据表明这种药物具有良好的治疗指数。甲磺酸 obatoclax 治疗白血病和淋巴瘤的 I 期试验确定了耐受性良好的治疗方案,并发现短暂的神经毒性是这种药物最常见的不良反应。在这些研究中,观察到了数量有限的客观反应,较大比例的治疗患者的血液学状况有所改善。然而,已发表的淋巴瘤和骨髓纤维化二期评估报告并未显示出强大的单药活性。正在进行的临床前和临床研究的新证据表明,甲磺酸奥巴曲克作为一种新型抗癌药的全部潜力可能在以下两个方面得以实现:(1) 合理的联合治疗;(2) 以治疗反应的分子预测指标为指导。通过了解 Obatoclax 反应的分子基础以及最佳治疗方案和适应症,可以进一步阐明甲磺酸 obatoclax 治疗血液恶性肿瘤的潜力。
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引用次数: 0
Hypofractionated external-beam radiation therapy (HEBRT) versus conventional external-beam radiation (CEBRT) in patients with localized prostate cancer: a systematic review and meta-analysis. 低分割外束放射治疗(HEBRT)与常规外束放射治疗(CEBRT)在局限性前列腺癌患者中的应用:一项系统综述和荟萃分析
Pub Date : 2013-01-01 Epub Date: 2013-03-07 DOI: 10.2147/CE.S41178
Tobias Engel Ayer Botrel, Otávio Clark, Antônio Carlos Lima Pompeo, Francisco Flávio Horta Bretas, Marcus Vinicius Sadi, Ubirajara Ferreira, Rodolfo Borges Dos Reis

Background: The purpose of this work was to conduct a systematic review and meta-analysis of all randomized controlled trials comparing the efficacy and side effect profile of hypofractionated versus conventional external-beam radiation therapy for prostate cancer.

Methods: Several databases were searched, including Medline, EmBase, LiLACS, and Central. The endpoints were freedom from biochemical failure and side effects. We performed a meta-analysis of the published data. The results are expressed as the hazard ratio (HR) or risk ratio (RR), with the corresponding 95% confidence interval (CI).

Results: The final analysis included nine trials comprising 2702 patients. Freedom from biochemical failure was reported in only three studies and was similar in patients who received hypofractionated or conventional radiotherapy (fixed effect, HR 1.03, 95% CI 0.88-1.20; P = 0.75), with heterogeneity [χ(2) = 15.32, df = 2 (P = 0.0005); I2 = 87%]. The incidence of acute adverse gastrointestinal events was higher in the hypofractionated group (fixed effect, RR 2.02, 95% CI 1.45-2.81; P < 0.0001). We also found moderate heterogeneity on this analysis [χ(2) = 7.47, df = 5 (P = 0.19); I2 = 33%]. Acute genitourinary toxicity was similar among the groups (fixed effect, RR 1.19, 95% CI 0.95-1.49; P = 0.13), with moderate heterogeneity [χ(2) = 5.83, df = 4 (P = 0.21); I2 = 31%]. The incidence of all late adverse events was the same in both groups (fixed effect, gastrointestinal toxicity, RR 1.17, 95% CI 0.79-1.72, P = 0.44; and acute genitourinary toxicity, RR 1.16, 95% CI 0.80-1.68, P = 0.44).

Conclusion: Hypofractionated radiotherapy in localized prostate cancer was not superior to conventional radiotherapy and showed higher acute gastrointestinal toxicity in this meta-analysis. Because the number of published studies is still small, future assessments should be conducted to clarify better the true role of hypofractionated radiotherapy in patients with prostate cancer.

背景:本研究的目的是对所有随机对照试验进行系统回顾和荟萃分析,比较低分割与常规外束放射治疗前列腺癌的疗效和副作用。方法:检索Medline、EmBase、LiLACS、Central等数据库。终点是没有生化失败和副作用。我们对发表的数据进行了荟萃分析。结果用风险比(HR)或风险比(RR)表示,并给出相应的95%置信区间(CI)。结果:最终分析包括9项试验,2702例患者。只有3项研究报告了生化失败的自由,在接受低分割或常规放疗的患者中也有类似的情况(固定效应,HR 1.03, 95% CI 0.88-1.20;P = 0.75),异质性[χ(2) = 15.32, df = 2 (P = 0.0005);I2 = 87%]。急性胃肠道不良事件的发生率在低分割组较高(固定效应,RR 2.02, 95% CI 1.45-2.81;P < 0.0001)。我们还发现该分析存在中度异质性[χ(2) = 7.47, df = 5 (P = 0.19);I2 = 33%]。两组间急性泌尿生殖系统毒性相似(固定效应,RR 1.19, 95% CI 0.95-1.49;P = 0.13),异质性中等[χ(2) = 5.83, df = 4 (P = 0.21);I2 = 31%]。两组的所有晚期不良事件发生率相同(固定效应,胃肠道毒性,RR 1.17, 95% CI 0.79-1.72, P = 0.44;急性泌尿生殖系统毒性,RR 1.16, 95% CI 0.80-1.68, P = 0.44)。结论:在本荟萃分析中,低分割放疗治疗局限性前列腺癌并不优于常规放疗,而且显示出更高的急性胃肠道毒性。由于已发表的研究数量仍然很少,未来的评估应该进行,以更好地阐明低分割放疗在前列腺癌患者中的真正作用。
{"title":"Hypofractionated external-beam radiation therapy (HEBRT) versus conventional external-beam radiation (CEBRT) in patients with localized prostate cancer: a systematic review and meta-analysis.","authors":"Tobias Engel Ayer Botrel,&nbsp;Otávio Clark,&nbsp;Antônio Carlos Lima Pompeo,&nbsp;Francisco Flávio Horta Bretas,&nbsp;Marcus Vinicius Sadi,&nbsp;Ubirajara Ferreira,&nbsp;Rodolfo Borges Dos Reis","doi":"10.2147/CE.S41178","DOIUrl":"https://doi.org/10.2147/CE.S41178","url":null,"abstract":"<p><strong>Background: </strong>The purpose of this work was to conduct a systematic review and meta-analysis of all randomized controlled trials comparing the efficacy and side effect profile of hypofractionated versus conventional external-beam radiation therapy for prostate cancer.</p><p><strong>Methods: </strong>Several databases were searched, including Medline, EmBase, LiLACS, and Central. The endpoints were freedom from biochemical failure and side effects. We performed a meta-analysis of the published data. The results are expressed as the hazard ratio (HR) or risk ratio (RR), with the corresponding 95% confidence interval (CI).</p><p><strong>Results: </strong>The final analysis included nine trials comprising 2702 patients. Freedom from biochemical failure was reported in only three studies and was similar in patients who received hypofractionated or conventional radiotherapy (fixed effect, HR 1.03, 95% CI 0.88-1.20; P = 0.75), with heterogeneity [χ(2) = 15.32, df = 2 (P = 0.0005); I2 = 87%]. The incidence of acute adverse gastrointestinal events was higher in the hypofractionated group (fixed effect, RR 2.02, 95% CI 1.45-2.81; P < 0.0001). We also found moderate heterogeneity on this analysis [χ(2) = 7.47, df = 5 (P = 0.19); I2 = 33%]. Acute genitourinary toxicity was similar among the groups (fixed effect, RR 1.19, 95% CI 0.95-1.49; P = 0.13), with moderate heterogeneity [χ(2) = 5.83, df = 4 (P = 0.21); I2 = 31%]. The incidence of all late adverse events was the same in both groups (fixed effect, gastrointestinal toxicity, RR 1.17, 95% CI 0.79-1.72, P = 0.44; and acute genitourinary toxicity, RR 1.16, 95% CI 0.80-1.68, P = 0.44).</p><p><strong>Conclusion: </strong>Hypofractionated radiotherapy in localized prostate cancer was not superior to conventional radiotherapy and showed higher acute gastrointestinal toxicity in this meta-analysis. Because the number of published studies is still small, future assessments should be conducted to clarify better the true role of hypofractionated radiotherapy in patients with prostate cancer.</p>","PeriodicalId":10764,"journal":{"name":"Core Evidence","volume":"8 ","pages":"1-13"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CE.S41178","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31425734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 20
Sugammadex as a reversal agent for neuromuscular block: an evidence-based review. 舒格迈司作为神经肌肉阻滞的逆转剂:循证综述。
Pub Date : 2013-01-01 Epub Date: 2013-09-25 DOI: 10.2147/CE.S35675
Stefan Josef Schaller, Heidrun Fink

Sugammadex is the first clinical representative of a new class of drugs called selective relaxant binding agents. It has revolutionized the way anesthesiologists think about drug reversal. Sugammadex selectively binds rocuronium or vecuronium, thereby reversing their neuromuscular blocking action. Due to its 1:1 binding of rocuronium or vecuronium, it is able to reverse any depth of neuromuscular block. So far, it has been approved for use in adult patients and for pediatric patients over 2 years. Since its approval in Europe, Japan, and Australia, further insight on its use in special patient populations and specific diseases have become available. Due to its pharmacodynamic profile, sugammadex, in combination with rocuronium, may have the potential to displace succinylcholine as the "gold standard" muscle relaxant for rapid sequence induction. The use of rocuronium or vecuronium, with the potential of reverse of their action with sugammadex, seems to be safe in patients with impaired neuromuscular transmission, ie, neuromuscular diseases, including myasthenia gravis. Data from long-term use of sugammadex is not yet available. Evidence suggesting an economic advantage of using sugammadex and justifying its relatively high cost for an anesthesia-related drug, is missing.

Sugammadex 是一类新型药物(选择性松弛剂结合剂)的首个临床代表。它彻底改变了麻醉医生对药物逆转的看法。舒甘麦可选择性地与罗库溴铵或维库溴铵结合,从而逆转它们的神经肌肉阻滞作用。由于其与罗库溴铵或维库溴铵的结合率为 1:1,因此能够逆转任何深度的神经肌肉阻滞。迄今为止,它已被批准用于成人患者和 2 岁以上的儿童患者。自其在欧洲、日本和澳大利亚获得批准后,人们对其在特殊患者群体和特定疾病中的使用有了进一步的了解。由于其药效学特征,苏加麦角与罗库溴铵联用可能会取代琥珀胆碱,成为快速序列诱导的 "金标准 "肌肉松弛剂。使用罗库溴铵或维库溴铵可能会与苏甘麦角的作用相反,但对于神经肌肉传导受损的患者(即神经肌肉疾病患者,包括重症肌无力患者)似乎是安全的。目前还没有长期使用舒甘麦的数据。目前还没有证据表明使用舒甘麦具有经济优势,也没有证据证明舒甘麦作为一种与麻醉相关的药物成本相对较高。
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引用次数: 0
Pancrelipase: an evidence-based review of its use for treating pancreatic exocrine insufficiency. 胰酶:其用于治疗胰腺外分泌功能不全的循证回顾。
Pub Date : 2012-01-01 Epub Date: 2012-07-19 DOI: 10.2147/CE.S26705
Kei Nakajima, Haruki Oshida, Toshitaka Muneyuki, Masafumi Kakei

Pancreatic exocrine insufficiency (PEI) is often observed in patients with pancreatic diseases, including chronic pancreatitis, cystic fibrosis, and tumors, or after surgical resection. PEI often results in malnutrition, weight loss and steatorrhea, which together increase the risk of morbidity and mortality. Therefore, nutritional interventions, such as low-fat diets and pancreatic enzyme replacement therapy (PERT), are needed to improve the clinical symptoms, and to address the pathophysiology of pancreatic exocrine insufficiency. PERT with delayed-release pancrelipase is now becoming a standard therapy for pancreatic exocrine insufficiency because it significantly improves the coefficients of fat and nitrogen absorption as well as clinical symptoms, without serious treatment-emergent adverse events. The major adverse events were tolerable gastrointestinal tract symptoms, such as stomach pain, nausea, and bloating. Fibrosing colonopathy, a serious complication, is associated with high doses of enzymes. Several pancrelipase products have been approved by the US Food and Drug Administration in recent years. Although many double-blind, placebo-controlled trials of pancrelipase products have been conducted in recent years, these studies have enrolled relatively few patients and have often been less than a few weeks in duration. Moreover, few studies have addressed the issue of pancreatic diabetes, a type of diabetes that is characterized by frequent hypoglycemia, which is difficult to manage. In addition, it is unclear whether PERT improves morbidity and mortality in such settings. Therefore, large, long-term prospective studies are needed to identify the optimal treatment for pancreatic exocrine insufficiency. The studies should also examine the extent to which PERT using pancrelipase improves mortality and morbidity. The etiology and severity of pancreatic exocrine insufficiency often differ among patients with gastrointestinal diseases or diabetes (type 1 and type 2), and among elderly subjects. Finally, although there is currently limited clinical evidence, numerous extrapancreatic diseases and conditions that are highly prevalent in the general population may also be considered potential targets for PERT and related treatments.

胰腺外分泌功能不全(PEI)常见于胰腺疾病患者,包括慢性胰腺炎、囊性纤维化和肿瘤,或手术切除后。PEI通常导致营养不良、体重减轻和脂肪漏,这些都增加了发病率和死亡率的风险。因此,需要营养干预,如低脂饮食和胰酶替代疗法(PERT),以改善临床症状,并解决胰腺外分泌功能不全的病理生理。延迟释放胰酶的PERT目前已成为治疗胰腺外分泌功能不全的标准治疗方法,因为它能显著改善脂肪和氮的吸收系数以及临床症状,且无严重的治疗不良事件。主要不良事件为可耐受的胃肠道症状,如胃痛、恶心和腹胀。纤维化性结肠病是一种严重的并发症,与高剂量的酶有关。近年来,美国食品和药物管理局批准了几种胰酶产品。尽管近年来进行了许多关于胰酶产品的双盲、安慰剂对照试验,但这些研究只招募了相对较少的患者,而且持续时间通常不到几周。此外,很少有研究涉及胰腺糖尿病的问题,这是一种以频繁低血糖为特征的糖尿病,难以控制。此外,目前尚不清楚PERT是否能改善这种情况下的发病率和死亡率。因此,需要大规模、长期的前瞻性研究来确定胰腺外分泌功能不全的最佳治疗方法。研究还应检查使用胰酶的PERT能在多大程度上改善死亡率和发病率。胰腺外分泌功能不全的病因和严重程度在胃肠道疾病或糖尿病患者(1型和2型)和老年人中往往不同。最后,尽管目前临床证据有限,但许多在普通人群中高度流行的胰腺外疾病和病症也可能被认为是PERT和相关治疗的潜在靶点。
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引用次数: 46
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