PARP inhibitors

PARP 抑制剂
  • 文章类型: Journal Article
    卵巢癌是最致命的妇科癌症。高级别浆液性上皮(HGSE)亚型是最具侵略性的,它通常出现在晚期,虽然筛查计划还没有被证明是有益的。高级阶段的管理(FIGOIII和IV),构成大多数诊断,通常包括铂类化疗和细胞减灭术(原发或间期),然后进行维持治疗.目前,晚期新诊断的HGSE卵巢癌的护理标准,根据国际医学协会,从前期的细胞减灭术开始,其次是铂类化疗(主要是卡铂和紫杉醇)和/或抗血管生成药物贝伐单抗,然后用聚(ADP-核糖)聚合酶(PARP)抑制剂加/不加/不加贝伐单抗维持治疗(续).PARP抑制剂的使用取决于患者的遗传特征,主要表现为乳腺癌基因(BRCA)突变和同源重组缺陷(HRD)状态。因此,建议在诊断时进行基因检测,以告知治疗和预后。根据不断发展的卵巢癌护理标准,一个治疗晚期卵巢癌的专家小组召开会议,就黎巴嫩晚期卵巢癌的治疗提出切实可行的建议;因为黎巴嫩公共卫生部目前适用的癌症治疗指南尚未更新,以反映PARP抑制剂的开发和批准带来的治疗模式转变。目前的工作回顾了PARP抑制剂(作为新诊断的晚期和铂敏感的复发性卵巢癌的维持)的主要临床试验,提出国际建议,并提出了最优局部实践的治疗算法。
    Ovarian cancer is the most lethal gynecologic cancer. The high grade serous epithelial (HGSE) subtype is the most aggressive and it often presents at advanced stages, while screening programs have not proven beneficial. Management of the advanced stages (FIGO III and IV), which constitute the majority of diagnoses, usually consists of platinum-based chemotherapy and cytoreductive surgery (primary or interval) followed by maintenance therapy. Currently, the standard-of-care for advanced newly diagnosed HGSE ovarian cancer, as per international medical societies, starts with upfront cytoreductive surgery, followed by platinum-based chemotherapy (mostly carboplatin and paclitaxel) and/or anti-angiogenic agent bevacizumab, then maintenance therapy with a poly(ADP-ribose) polymerase (PARP) inhibitor with/without/or bevacizumab (continued). PARP inhibitor use depends on the patient\'s genetic signature, mainly the breast cancer gene (BRCA) mutation and the homologous recombination deficiency (HRD) status. Therefore, genetic testing is recommended at diagnosis to inform treatment and prognosis. In line with the evolving standard-of-care for ovarian cancer, a panel of experts in treating advanced ovarian cancer convened to lay down practical recommendations on the management of advanced ovarian cancer in Lebanon; since the currently applicable guidelines by the Lebanese Ministry of Public Health for cancer treatment have not been updated yet to reflect the treatment paradigm shift brought upon by the development and approval of PARP inhibitors. The current work reviews the leading clinical trials on PARP inhibitors (as maintenance for newly diagnosed advanced and platinum-sensitive relapsed ovarian cancer), presents international recommendations, and proposes treatment algorithms for optimal local practice.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    目的:我们的目的是就晚期卵巢癌最有争议的治疗问题达成共识。
    方法:使用标称组和德尔菲技术。由5名专家组成的指导委员会分析了晚期卵巢癌的当前管理,确定的争议,批判性地分析了证据,并为临床医生制定了指导性声明。随后,选择了一个由15名专家组成的小组,通过两轮Delphi测试与声明的一致性。项目以4分的李克特量表从1(完全不同意)到4(完全同意)进行评分。在第一轮和第二轮中,如果≥70%的答案属于第1类或第4类,则认为是共识。
    结果:总体而言,在以下领域纳入了112项陈述:1)生物标志物和遗传性卵巢癌;2)一线治疗;3)铂可能是最佳选择的复发性疾病;4)聚(二磷酸腺苷-核糖)聚合酶(PARP)抑制剂后设置。在第一轮Delphi中,37项声明达成共识,因此没有进入第二轮。第二轮之后,另有18项声明达成共识。有46个共识是同意的,有9个共识是不同意的。
    结论:通过使用的方法,大约一半的声明达成了共识。这项工作的结果可能有助于解决有关晚期卵巢癌管理的最有争议的问题。
    Our aim was to reach a consensus on the management of the most controversial issues of advanced ovarian cancer.
    Nominal group and Delphi techniques were used. A steering committee of 5 experts analyzed current management of advanced ovarian cancer, identified controversies, critically analyzed the evidence, and formulated guiding statements for clinicians. Subsequently, a panel of 15 experts was selected to test agreement with the statements through two Delphi rounds. Items were scored on a 4-point Likert scale from 1 (totally disagree) to 4 (totally agree). In the first and second rounds, consensus was considered if ≥70% of answers pertained to category 1 or category 4.
    Overall, 112 statements were incorporated in the following areas: 1) biomarkers and hereditary ovarian cancer; 2) first-line treatment; 3) recurrent disease when platinum might be the best option; and 4) post-poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors setting. In the first Delphi round, 37 statements reached consensus and did thus not pass to the second round. After the second round, another 18 statements reached consensus. Forty-six of the consensus were with the agreement and 9 with the disagreement.
    Through the methodology used, a consensus was reached in approximately half of the statements. The results of this work may be useful in addressing the most controversial issues on the management of advanced ovarian cancer.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: English Abstract
    目的:尽管治疗适应症越来越多,除了每种物质的SmPC规定之外,没有关于PARP抑制剂管理的具体建议.进行了Delphi法国共识,以建立实用指南,以满足医疗保健专业人员和患者确定的需求。
    方法:遵循Delphi方法,由17名专家组成的多学科指导委员会起草了优化PARP抑制剂管理的声明.这些陈述提交给参与PARP抑制剂治疗患者的临床医生的独立和匿名投票。
    结果:本文提供了有关以下主题的52项陈述:开始和治疗;不良事件的管理(血液学影响,胃肠道的影响,肾脏影响,肺效应,皮肤效应,高血压,失眠,疲劳,头晕);特殊人群和情况;与患者沟通;依从性。经过3轮投票后,有49项声明获得了选民共识。血液学家和肾病学家通过起草关于继发性白血病和肾病毒性发生风险的专家意见来补充这项任务。
    结论:本文是关于PARP抑制剂实际管理的第一个Delphi共识。本文提出的务实建议应该可以更好地管理PARP抑制剂的副作用,从而防止早期停药,并通过保持生活质量来提高患者的依从性。
    OBJECTIVE: Despite an increasing number of therapeutic indications, there are no specific recommendations regarding the management of PARP inhibitors other than what is specified in the SmPC of each substance. A Delphi French consensus was conducted to establish practical guidelines to meet the needs identified by healthcare professionals and patients.
    METHODS: Following the Delphi method, statements to optimize PARP inhibitor management were drafted by a multidisciplinary Steering Committee made up of 17 experts. These statements were submitted to the independent and anonymous vote of clinicians involved in treating patients on PARP inhibitors.
    RESULTS: This article presents 52 statements on the following topics: initiation and treatment; management of adverse events (hematological effects, gastrointestinal effects, renal effects, pulmonary effects, cutaneous effects, hypertension, insomnia, fatigue, dizziness); special populations and situations; communication with the patient; adherence. Forty-nine statements obtained voter consensus after 3 voting rounds. A hematologist and a nephrologist supplemented this task by drafting an expert opinion on the risk of occurrence of secondary leukemia and nephrological toxicity.
    CONCLUSIONS: This paper is the first Delphi consensus on the practical management of PARP inhibitors. The pragmatic recommendations resulting from this paper should make it possible to manage the side effects of PARP inhibitors better and thus prevent early treatment discontinuation and improve patient adherence by preserving quality of life.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Journal Article
    大多数晚期患者,高级别上皮-肿瘤卵巢癌(EOC)对铂类化疗的初始治疗反应良好;然而,高达80%的患者将经历复发。聚(ADP-核糖)聚合酶(PARP)抑制剂已被确立为护理维持治疗的标准,以延长缓解时间并防止对一线铂化疗产生反应后的复发。Olaparib和niraparib是目前在加拿大批准用于一线维护的PARP抑制剂。选择维持治疗需要考虑患者和肿瘤因素,种系和体细胞突变的存在,预期的药物毒性概况,和治疗准入。本文讨论了PARP抑制剂一线维持治疗晚期患者的临床证据,高级EOC,并提供共识声明和治疗算法,以帮助加拿大肿瘤学家在加拿大EOC治疗环境中选择和使用PARP抑制剂。
    The majority of patients with advanced, high-grade epithelial-tubo ovarian cancer (EOC) respond well to initial treatment with platinum-based chemotherapy; however, up to 80% of patients will experience a recurrence. Poly(ADP-ribose) Polymerase (PARP) inhibitors have been established as a standard of care maintenance therapy to prolong remission and prevent relapse following a response to first-line platinum-chemotherapy. Olaparib and niraparib are the PARP inhibitors currently approved for use in the first-line maintenance setting in Canada. Selection of maintenance therapy requires consideration of patient and tumour factors, presence of germline and somatic mutations, expected drug toxicity profile, and treatment access. This paper discusses the current clinical evidence for first-line PARP inhibitor maintenance therapy in patients with advanced, high-grade EOC and presents consensus statements and a treatment algorithm to aid Canadian oncologists on the selection and use of PARP inhibitors within the Canadian EOC treatment landscape.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Journal Article
    在肿瘤学会诊中被诊断为管腔转移性乳腺癌(MBC)的大多数患者都是老年人。老年患者MBC的特征是激素受体(HR)表达百分比较高,人表皮生长因子受体2(HER2)表达较低。由于缺乏支持决策过程的确凿证据,因此对这些患者进行哪种治疗的决定很复杂。本文的目的是回顾老年人腔MBC治疗的科学证据。为此,西班牙医学肿瘤学会(SEOM)的肿瘤科,西班牙乳腺癌研究小组(GEICAM)和SOLTI小组任命了一组专家,他们共同制定了共识建议,以优化该人群的治疗.结论是,仅患者的实际年龄不应指导治疗决策,并且在建立治疗之前,应尽可能进行老年综合评估(CGA)。老年人群的治疗选择应考虑患者的基线状态,每种治疗的预期益处和毒性,以及治疗毒性对患者生活质量和功能的影响。
    Most patients diagnosed with luminal metastatic breast cancer (MBC) who are seen in oncology consultations are elderly. MBC in elderly patients is characterized by a higher percentage of hormone receptor (HR) expression and a lower expression of human epidermal growth factor receptor 2 (HER2). The decision regarding which treatment to administer to these patients is complex due to the lack of solid evidence to support the decision-making process. The objective of this paper is to review the scientific evidence on the treatment of elderly patients with luminal MBC. For this purpose, the Oncogeriatrics Section of the Spanish Society of Medical Oncology (SEOM), the Spanish Breast Cancer Research Group (GEICAM) and the SOLTI Group appointed a group of experts who have worked together to establish consensus recommendations to optimize the treatment of this population. It was concluded that the chronological age of the patient alone should not guide therapeutic decisions and that a Comprehensive Geriatric Assessment (CGA) should be performed whenever possible before establishing treatment. Treatment selection for the elderly population should consider the patient\'s baseline status, the expected benefit and toxicity of each treatment, and the impact of treatment toxicity on the patient\'s quality of life and functionality.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Journal Article
    BRCA1 and BRCA2 gene pathogenic variants account for most hereditary breast cancer and are increasingly used to determine eligibility for PARP inhibitor (PARPi) therapy of BRCA-related cancer. Because issues of BRCA testing in clinical practice now overlap with both preventive and therapeutic management, updated and comprehensive practice guidelines for BRCA genotyping are needed. The integrative recommendations for BRCA testing presented here aim to (1) identify individuals who may benefit from genetic counselling and risk-reducing strategies; (2) update germline and tumour-testing indications for PARPi-approved therapies; (3) provide testing recommendations for personalised management of early and metastatic breast cancer; and (4) address the issues of rapid process and tumour analysis. An international group of experts, including geneticists, medical and surgical oncologists, pathologists, ethicists and patient representatives, was commissioned by the French Society of Predictive and Personalised Medicine (SFMPP). The group followed a methodology based on specific formal guidelines development, including (1) evaluating the likelihood of BRCAm from a combined systematic review of the literature, risk assessment models and expert quotations, and (2) therapeutic values of BRCAm status for PARPi therapy in BRCA-related cancer and for management of early and advanced breast cancer. These international guidelines may help clinicians comprehensively update and standardise BRCA testing practices.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Sci-hub)

公众号