间歇性应用来曲唑增加輔助医治能不能改进闭经后初期乳腺癌结果?

南亚先生 2021年11月17日10:03:07
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间歇性应用来曲唑增加輔助医治能不能改进闭经后初期乳腺癌结果? 。
来曲唑 FEMARA摘 要:来曲唑芙瑞。【微信号码:yaodaoyaofang】:《柳叶刀》肿瘤学来源于:SIBCS针对绝经期后初期乳腺癌女士,必须应用来曲唑(芬芳酶抑制剂)提升輔助内分泌治疗防止反复发,可是长时间应用来曲唑很有可能引起起承受药品。依据以往乳腺癌细胞模型研究发现,持续应用来曲唑引起起的承受药品,可被间歇性应用来曲唑而反转。因而,有学者假定,间歇性应用来曲唑与持续应用来曲唑对比,针对绝经期后初期乳腺癌女士的提升輔助内分泌治疗可以改进结果。2022年11月17日,美国《柳叶刀》肿瘤学手册线上发布国际性乳腺癌科学研究学组(IBCSG)多核心非盲任意平行面三期科学研究(SOLE)汇报,较为了间歇性或持续应用来曲唑提升闭经后初期乳腺癌女士輔助内分泌治疗的有效和安全防护特点。该多核心非盲任意平行面三期科学研究(SOLE)于2007年12月5日~2012年10月8日在2两个我国240个核心(学术研究、一级、二级、三级医疗中心)入组一切年纪、生长激素蛋白激酶呈阳性、淋巴结节呈阳性、可手术乳腺癌、已接纳部分医治(手术±放射性物质治疗法)并顺利完成4~六年輔助内分泌治疗(包含他莫昔芬)的绝经期后女士4884例,入组时无乳腺癌临床医学直接证据、无病症反复发直接证据,按1∶1任意分派接纳持续应用来曲唑(每天2.5mg内服5年)或间断应用来曲唑(第一~四年每天2.5mg内服9个月停止使用3个月→第5年每天2.5mg内服12个月)。由关键学者或特定者在分别核心根据国际性乳腺癌科学研究学组互联网技术操作系统开展随机分组,依据以往内分泌治疗类型(仅用芬芳酶抑制剂、仅用可选择性雌激素受体调理剂、二者协同)开展分层次,区组尺寸为四,并按组织开展均衡。医治分派非盲。关键终端为没病存活,根据意愿医治标准应用分层次多数秩检测开展剖析。参加科学研究时间范围,想要接收医治群体当中,全部具体接纳科学研究方法治疗的病患者均开展安全性特点剖析。该科研在美政府临床实验数据库查询、欧盟国家临床实验数据库查询的申请注册序号分別为:NCT 00553410、EudraCT 2007-001370-88,而且已经开展病患者长期性随诊。该探究由诺华制药和国际性乳腺癌科学研究工作组(IBCSG)给予支助。历经负相关随诊60(四分位距:53~72)个月,想要接收医治4851例:间歇性组2425例没病存活概率85.8%(95%可信区间:84.2~87.2)持续组2426例没病存活概率87.5%(95%可信区间:86.0~88.8)反复发风险比:1.08(95%可信区间:0.93~1.26,P=0.31)具体接纳医治4828例,在其中间歇性组2417例、持续组2411例,欠佳(过虑词)汇报如预测分析期待且类似,最普遍的3~5级欠佳(过虑词):血压高:584例(24%)、517例(21%)关节疼:136例(6%、151例(6%)脑栓塞:24例(1%)、30例(1%)脑溢血:9例(<1%)、7例(<1%)心脏缺血:19例(1%)、21例(1%)科学研究医治时间范围过世23例(<1%),在其中间歇性组13例(<1%)、持续组10例(<1%)。因而,针对绝经期后生长激素蛋白激酶呈阳性乳腺癌病患者,提升间歇性应用来曲唑与持续应用来曲唑对比,并无法改进没病存活。但是,应用来曲唑提升輔助内分泌治疗(包含间歇性给药)的代替方式 也许有安全性特点和政治经济学的实际意义,而且针对很有可能必须临时性终断来曲唑医治的可选择性病患者,SOLE科学研究結果确认其安全性特点。对于此事,加利福尼亚州希望之城我国医科学研究核心、洛杉矶市微生物医科学研究研究室(坐落于加利福尼亚大学港口医科学研究核心)发布当期评价【 手机微信:yaodaoyaofang】:间歇性来曲唑輔助医治的多元性,觉得SOLE科学研究结论为提升輔助内分泌失调辅疗给予了新直接证据,可是该科学研究入组了以往使用过他莫昔芬(可选择性雌激素受体调理剂)的病患者,使该科学研究结论的表述越来越复杂。依据亚组分析,以往仅使用过芬芳酶抑制剂有益于间歇性组,以往仅使用过可选择性雌激素受体调理剂有益于持续组,尽管统计学意义并不大,可是临床表现依然需要考虑到。Extended adjuvant intermittent letrozole versus continuous letrozole in postmenopausal women with breast cancer (SOLE): a multicentre, open-label, randomised, phase 3 trial.Marco Colleoni, Weixiu Luo, Per Karlsson, Jacquie Chirgwin, Stefan Aebi, Guy Jerusalem, Patrick Neven, Erika Hitre, Marie-Pascale Graas, Edda Simoncini, Claus Kamby, Alastair Thompson, Sibylle Loibl, Joaquín Gavilá, Katsumasa Kuroi, Christian Marth, Bettina Müller, Seamus O\'Reilly, Vincenzo Di Lauro, Andrea Gombos, Thomas Ruhstaller, Harold Burstein, Karin Ribi, Jürg Bernhard, Giuseppe Viale, Rudolf Maibach, Manuela Rabaglio-Poretti, Richard D Gelber, Alan S Coates, Angelo Di Leo, Meredith M Regan, Aron Goldhirsch; SOLE Investigators.International Breast Cancer Study Group, Milan, Italy; European Institute of Oncology, Milan, Italy; International Breast Cancer Study Group Statistical Center, Boston, MA, USA; Dana-Farber Cancer Institute, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Harvard T H Chan School of Public Health, Boston, MA, USA; University of Gothenburg, Gothenburg, Sweden; Australia and New Zealand Breast Cancer Trials Group, Box Hill and Maroondah Hospitals, Monash University, Melbourne, VIC, Australia; Lucerne Canton Hospital, Lucerne, Switzerland; Centre Hospitalier Universitaire de Liège, Liège University, Liège, Belgium; Multidisciplinary Breast Center, University Hospitals, Katholieke Universiteit Leuven, Leuven, Belgium; National Institute of Oncology, Budapest, Hungary; Centre Hospitalier Chrétien Clinique St Joseph, Liège, Belgium; ASST Spedali Civili di Brescia, Brescia, Italy; Danish Breast Cancer Group, Rigshospitalet, Copenhagen, Denmark; Scottish Cancer Trials Breast Group, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; German Breast Group, Neu-Isenburg, Germany; SOLTI Group, Fundación Instituto Valenciano de Oncologia, Valencia, Spain; Japan Breast Cancer Research Group, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan; Austrian Breast & Colorectal Cancer Study Group, Medical University Innsbruck, Innsbruck, Austria; Chilean Cooperative Group for Oncologic Research, Providencia, Santiago, Chile; Cancer Trials Ireland and Cork University Hospital, Cork, Ireland; Centro di Riferimento Oncologico di Aviano, Aviano, Italy; Institute Jules Bordet, Brussels, Belgium; Swiss Group for Clinical Cancer Research, Breast Center St Gallen, St Gallen, Switzerland; International Breast Cancer Study Group Coordinating Center, Bern, Switzerland; Bern University Hospital, Inselspital, Bern, Switzerland; University of Milan, Milan, Italy; Frontier Science & Technology Research Foundation, Boston, MA, USA; University of Sydney, Sydney, NSW, Australia; Hospital of Prato-AUSL Toscana Centro, Istituto Toscano Tumori, Prato, Italy.BACKGROUND: In animal models of breast cancer, resistance to continuous use of letrozole can be reversed by withdrawal and reintroduction of letrozole. We therefore hypothesised that extended intermittent use of adjuvant letrozole would improve breast cancer outcome compared with continuous use of letrozole in postmenopausal women.METHODS: We did the multicentre, open-label, randomised, parallel, phase 3 SOLE trial in 240 centres (academic, primary, secondary, and tertiary care centres) in 22 countries. We enrolled postmenopausal women of any age with hormone receptor-positive, lymph node-positive, and operable breast cancer for which they had undergone local treatment (surgery with or without radiotherapy) and had completed 4-6 years of adjuvant endocrine therapy. They had to be clinically free of breast cancer at enrolment and without evidence of recurrent disease at any time before randomisation. We randomly assigned women (1:1) to treatment groups of either continuous use of letrozole (2.5 mg/day orally for 5 years) or intermittent use of letrozole (2.5 mg/day orally for 9 months followed by a 3-month break in years 1-4 and then 2.5 mg/day during all 12 months of year 5). Randomisation was done by principal investigators or designee at respective centres through the internet-based system of the International Breast Cancer Study Group, was stratified by type of previous endocrine therapy (aromatase inhibitors only vs selective oestrogen receptor modulators only vs both therapies), and used permuted block sizes of four and institutional balancing. No one was masked to treatment assignment. The primary endpoint was disease-free survival, analysed by the intention-to-treat principle using a stratified log-rank test. All patients in the intention-to-treat population who initiated protocol treatment during their period of trial participation were included in the safety analyses. This study is registered with ClinicalTrials.gov, number NCT00553410, and EudraCT, number 2007-001370-88; and long-term follow-up of patients is ongoing.FINDINGS: Between Dec 5, 2007, and Oct 8, 2012, 4884 women were enrolled and randomised after exclusion of patients at a non-adherent centre, found to have inadequate documentation of informed consent, immediately withdrew consent, or randomly assigned to intervention groups in error. 4851 women comprised the intention-to-treat population that compared extended intermittent letrozole use (n=2425) with continuous letrozole use (n=2426). After a median follow-up of 60 months (IQR 53-72), disease-free survival was 85.8% (95% CI 84.2-87.2) in the intermittent letrozole group compared with 87.5% (86.0-88.8) in the continuous letrozole group (hazard ratio 1.08, 95% CI 0.93-1.26; p=0.31). Adverse events were reported as expected and were similar between the two groups. The most common grade 3-5 adverse events were hypertension (584 [24%] of 2417 in the intermittent letrozole group vs 517 [21%] of 2411 in the continuous letrozole group) and arthralgia (136 [6%] vs 151 [6%]). 54 patients (24 [1%] in the intermittent letrozole group and 30 [1%] in the continuous letrozole group) had grade 3-5 CNS cerebrovascular ischaemia, 16 (nine [<1%] vs seven [<1%]) had grade 3-5 CNS haemorrhage, and 40 (19 [1%] vs 21 [1%]) had grade 3-5 cardiac ischaemia. In total, 23 (<1%) of 4851 patients died while on trial treatment (13 [<1%] of 2417 patients in the intermittent letrozole group vs ten [<1%] of 2411 in the continuous letrozole group).INTERPRETATION: In postmenopausal women with hormone receptor-positive breast cancer, extended use of intermittent letrozole did not improve disease-free survival compared with continuous use of letrozole. An alternative schedule of extended adjuvant endocrine therapy with letrozole, including intermittent administration, might be feasible and the results of the SOLE trial support the safety of temporary treatment breaks in selected patients who might require them.义务【微&信:yaodaoyaofang】:恶性肿瘤新闻资讯-Ruby来曲唑 FEMARA网上订购方式-药道全世界,助推性命。印度的全世界海淘药店:来曲唑的功效和作用。

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