Core Evidence evaluates the evidence underlying the potential place in therapy of drugs throughout their development lifecycle from preclinical to postlaunch. The focus of each review is to evaluate the case for a new drug or class in outcome terms in specific indications and patient groups    The emerging evidence on new drugs is reviewed at key stages of development and evaluated against unmet needs

Core Evidence evaluates the evidence supporting the potential therapeutic role of drugs throughout their development lifecycle, from preclinical stages to post-launch. Each review focuses on assessing the case for a new drug or class in terms of outcomes for specific indications and patient groups. Emerging evidence on new drugs is reviewed at key stages of development and evaluated against unmet medical needs.

《Core Evidence》期刊评估药物在其开发生命周期内（从临床前到上市后）在治疗中的潜在应用证据。每篇评审的重点是评估新药或药物类别在特定适应症和患者群体中的疗效。新药的最新证据在开发的关键阶段进行审查，并与未满足的需求进行对比评估。

Core Evidence

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); I 2 = 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); I 2 = 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); I 2 = 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. Keywords: hypofractionated, radiotherapy, prostate cancer, systematic review, acute radiation effects

Tobias Engel Ayer Botrel

Otávio Clark

Antônio Carlos Lima Pompeo

Francisco Flávio Horta Bretas

Marcus Vinicius Sadi

Ubirajara Ferreira

Rodolfo Borges Dos Reis

Core evidence

Hypofractionated external-beam radiation therapy (HEBRT) versus conventional external-beam radiation (CEBRT) in patients with localized prostate cancer: a systematic review and meta-analysis

局部前列腺癌患者中大分割外照射放疗（HEBRT）与常规外照射放疗（CEBRT）的比较：一项系统综述和Meta分析

Abstract: 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. Keywords: obatoclax, leukemia, lymphoma, myelofibrosis, BCL-2, BH3 mimetic

Carolyn A Goard

Aaron Schimmer

An evidence-based review of obatoclax mesylate in the treatment of hematological malignancies

基于证据的奥巴托克拉甲磺酸盐在血液系统恶性肿瘤治疗中的综述

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. Keywords: castration-resistant prostate cancer, enzalutamide, MDV3100, antiandrogen, androgen receptor

Emmanuel Antonarakis

None Golshayan

Enzalutamide: an evidence-based review of its use in the treatment of prostate cancer

恩扎卢胺：其在前列腺癌治疗中应用的循证综述

Abstract: 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. Keywords: ibrutinib, B-cell receptor, chronic lymphocytic leukemia, Bruton's tyrosine kinase

Javier Pinilla-Ibarz

Julio C. Chavez

Eva Sahakian

Ibrutinib: an evidence-based review of its potential in the treatment of advanced chronic lymphocytic leukemia

伊布替尼：其在晚期慢性淋巴细胞白血病治疗中的潜在作用基于证据的综述

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.

Mitchell Rosner

None Bowman

Lixivaptan &amp;ndash; an evidence-based review of its clinical potential in the treatment of hyponatremia

利西伐坦——基于证据的临床潜力综述：治疗低钠血症

Chronic thromboembolic pulmonary hypertension (CTEPH) is classified as group-4 pulmonary hypertension caused by organized thrombi in pulmonary arteries and vasculopathy in nonoccluded areas leading to right heart failure and death. In addition to chronic anticoagulation therapy, each patient with CTEPH should receive treatment assessment starting with evaluation for pulmonary endarterectomy (PEA), which is the guideline recommended treatment. There is increasing experience with balloon pulmonary angioplasty (BPA) for inoperable patients; this option, like PEA, is reserved for specialized centers with expertise in this treatment method. Inoperable patients are candidates for targeted drug therapy. Riociguat remains the only approved medical therapy for CTEPH patients deemed inoperable or with persistent pulmonary hypertension after PEA. The role of riociguat therapy preoperatively or in tandem with BPA is currently under investigation. The purpose of this review is to evaluate the safety and efficacy of riociguat in the treatment of CTEPH.

Sahai Donaldson

Richard Ogunti

Angesom Kibreab

Alem Mehari

&lt;p&gt;Riociguat in the Treatment of Chronic Thromboembolic Pulmonary Hypertension: An Evidence-Based Review of Its Place in Therapy&lt;/p&gt;

利奥西呱在慢性血栓栓塞性肺动脉高压治疗中的应用：基于证据的其在疗法中的地位综述

Introduction Antineoplastic drugs may induce several side effects, including chemotherapy-induced nausea and vomiting (CINV). Two neurotransmitters play a central role in mediating the emetic response: serotonin acting on the 5HT3 receptor and the substance P targeting the NK1 receptor. Indeed, a combination of a 5HT3 receptor antagonist (5HT3-RA) and a NK1 receptor antagonist (NK1-RA) together with dexamethasone has been shown to be very effective. In fact, this combination is actually widely used and recommended for CINV prophylaxis for highly emetogenic cisplatin-based adriamycin/cyclophosphamide (AC) and carboplatin-based regimens. NEPA (netupitant/palonosetron) is the only fixed combination antiemetic available and it is composed by the long-lasting second-generation 5HT3-RA palonosetron and the highly selective NK1-RA netupitant. Aim The aims of this short review were to analyze the role of NEPA in CINV prophylaxis and management taking in account the risk factors related to the patient and to the antineoplastic treatment. Evidence Review CINV development is not only correlated to the emetogenic potential of the antineoplastic drugs but is also very influenced by the patient characteristics and history, such as gender, age, alcohol intake, nausea during pregnancy and motion sickness. In pivotal and post-registration studies, NEPA has demonstrated to be effective and safe in both highly and moderately emetogenic chemotherapy. Conclusion A proper assessment of both chemotherapy- and patient-related risk factors is paramount to properly evaluate an appropriate prophylaxis of CINV and NEPA by simplifying the therapy, guarantees fully adherence to antiemetic guidelines, and consequently improves the control of CINV, especially in high risk patients.

Vito Lorusso

Anna Russo

Francesco Giotta

Paolo Codega

&lt;p&gt;Management of Chemotherapy-Induced Nausea and Vomiting (CINV): A Short Review on the Role of Netupitant-Palonosetron (NEPA)&lt;/p&gt;

化疗引起的恶心和呕吐(CINV)的管理：奈妥吡坦-帕洛诺司琼(NEPA)作用的简要综述

Selective blockade of the integrins and mucosal adhesion molecules is a promising therapeutic strategy for ulcerative colitis (UC). Vedolizumab (VDZ), a humanized IgG1 monoclonal antibody against α4β7 integrin, selectively blocks the trafficking of the leukocytes into the gastrointestinal tract through its binding with the α4β7 integrin.In this review, we provide an overview of the unique mechanism of VDZ, along with its efficacy, safety, and pharmacokinetic and pharmacodynamic data obtained from clinical trials, observational studies, and meta-analyses.A positive exposure-efficacy relationship with regard to clinical remission and clinical response was apparent in VDZ induction therapy. No drug-specific safety signals are currently available.VDZ has been shown to be effective as first- or second-line induction and maintenance therapy in UC.VDZ is a safe and effective treatment option for patients with UC. Prolonged VDZ induction therapy may contribute to improved outcomes in patients with UC, particularly those previously treated with tumor necrosis factor-α. Prospective head-to-head study of VDZ and other biologics would alter the positioning of VDZ much more clearly.

Noritaka Takatsu

Takashi Hisabe

Daijiro Higashi

Toshiharu Ueki

Toshiyuki Matsui

&lt;p&gt;Vedolizumab in the Treatment of Ulcerative Colitis: An Evidence-Based Review of Safety, Efficacy, and Place of Therapy&lt;/p&gt;

<p>维多珠单抗在溃疡性结肠炎治疗中的应用：基于证据的安全性、疗效及治疗地位的综述</p>

Oral anticoagulant therapy for stroke prevention in atrial fibrillation patients has been remarkably changed by the introduction of non-vitamin k oral anticoagulants (NOAC). Apixaban was the third NOAC introduced to clinical practice. Aim was to outline the current evidence for Apixaban in stroke prevention in atrial fibrillation patients in the randomized trials and real-world data. Apixaban has been shown to be superior to warfarin in preventing stroke and systemic embolism and causes significantly less major bleeding based on large randomized trials. These data are confirmed in real-world studies. Apixaban has been shown to be safe and effective in atrial fibrillation patients in acute coronary syndrome or undergoing PCI in combination with a P2Y12 inhibitor. Regarding expanded use of apixaban also in valvular heart disease patients, there is still missing knowledge in relation to the safety and efficacy of apixaban which is being addressed by ongoing randomized clinical trials.

Julia Seeger

Jochen Wöhrle

&lt;p&gt;Apixaban: An Update of the Evidence for Its Place in the Prevention of Stroke in Patients with Atrial Fibrillation&lt;/p&gt;

阿哌沙班：其在心房颤动患者中风预防中的地位的证据更新

Abstract: Human epidermal growth factor receptor 2 (HER2)-positive breast cancer is a distinct subset of breast cancer that results from overexpression of HER2 protein. Pertuzumab—a recombinant humanized monoclonal antibody that binds to the extracellular dimerization domain II of HER2—was recently approved for adjuvant therapy and neoadjuvant therapy of HER2-positive early breast cancer. As pertuzumab and trastuzumab bind to different domains of the extracellular dimerization domain of HER2, a combination therapy of pertuzumab and trastuzumab is beneficial for the treatment of metastatic cancer, advanced local cancer, or early cancer by dual HER2 blockage. Many clinical trials have been performed using pertuzumab for breast cancer patients; these include the CLEOPATRA trial for palliative therapy, the APHINITY trial for adjuvant therapy, and the NeoSphere and the TRYPHAENA trials for neoadjuvant therapy. These trials revealed pertuzumab to be a safe and effective drug regardless of the patient age and hormone receptor status. Notably, pertuzumab use was associated with severe cardiac toxicity in some cases; however, the risk of pertuzumab-induced cardiac dysfunction was low. The most common adverse effect associated with pertuzumab-use was diarrhea, but most cases were not severe. Several different chemotherapeutic agents have been investigated to determine optimal chemotherapeutic combinations for dual HER2 blockage. Some exploratory analyses indicate that pertuzumab treatment offered little benefit to patients with node-negative and small primary tumors; pertuzumab treatment was also found not be cost-effective. Further research will reveal the appropriate usage of pertuzumab for treating a subset of eligible patients. Keywords: pertuzumab, HER2, breast cancer, trastuzumab

Kei Ishii

Nao Morii

Hiroyasu Yamashiro

&lt;p&gt;Pertuzumab in the treatment of HER2-positive breast cancer: an evidence-based review of its safety, efficacy, and place in therapy&lt;/p&gt;

帕妥珠单抗在HER2阳性乳腺癌治疗中的应用：基于证据的安全性、疗效及治疗地位综述

Publication Information	Publisher: Dove Medical Press Ltd.，Publishing cycle: ，Journal Type: journal，Open Access Journals: No
Basic data	Year of publication: 2005，Proportion of original research papers: 0.00%，Self Citation Rate:N.A.， Gold OA Rate: 83.33%

Core Evidence

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Hypofractionated external-beam radiation therapy (HEBRT) versus conventional external-beam radiation (CEBRT) in patients with localized prostate cancer: a systematic review and meta-analysis

An evidence-based review of obatoclax mesylate in the treatment of hematological malignancies

Enzalutamide: an evidence-based review of its use in the treatment of prostate cancer

Ibrutinib: an evidence-based review of its potential in the treatment of advanced chronic lymphocytic leukemia

Lixivaptan – an evidence-based review of its clinical potential in the treatment of hyponatremia

<p>Riociguat in the Treatment of Chronic Thromboembolic Pulmonary Hypertension: An Evidence-Based Review of Its Place in Therapy</p>

<p>Management of Chemotherapy-Induced Nausea and Vomiting (CINV): A Short Review on the Role of Netupitant-Palonosetron (NEPA)</p>

<p>Vedolizumab in the Treatment of Ulcerative Colitis: An Evidence-Based Review of Safety, Efficacy, and Place of Therapy</p>

<p>Apixaban: An Update of the Evidence for Its Place in the Prevention of Stroke in Patients with Atrial Fibrillation</p>

<p>Pertuzumab in the treatment of HER2-positive breast cancer: an evidence-based review of its safety, efficacy, and place in therapy</p>