福莫司汀(Fotemustine) - 药物靶点：DNA_在研适应症：脑癌_专利_临床

概要

基本信息

药物类型

小分子化药

别名

(+-)-Diethyl (1-(3-(2-chloroethyl)-3-nitrosoureido)ethyl)phosphonate、Diethyl-1-(3-(2-chloroethyl)-3-nitrosoureido)ethylphosphonate、Fotemustine (INN/BAN)

+ [8]

靶点

DNA

作用方式

抑制剂

作用机制

DNA抑制剂(DNA抑制剂)、DNA烷化剂

治疗领域

肿瘤神经系统疾病

在研适应症

脑癌

非在研适应症

非小细胞肺癌葡萄膜黑色素瘤

原研机构-

在研机构

Les Laboratoires Servier SAS

非在研机构

Servier Pharmaceuticals LLC

权益机构-

最高研发阶段批准上市

首次获批日期-

最高研发阶段(中国)批准上市

特殊审评-

登录后查看时间轴

结构/序列

分子式C9H19ClN3O5P

InChIKeyYAKWPXVTIGTRJH-UHFFFAOYSA-N

CAS号92118-27-9

关联

19

项与福莫司汀相关的临床试验

EUCTR2012-003618-15-IT

/ Not yet recruiting临床2期IIT

Multicenter, randomized, non-comparative, open-label phase II trial on the efficacy of Ortataxel and Fotemustine in recurrent glioblastoma

开始日期2013-09-17

申办/合作机构-

NCT01983124

/ Completed临床2期IIT

A Phase II Single-arm Study for the Treatment After Recurrence of Advanced Melanoma Patients Harboring the V600BRAF Mutation and Pretreated With Vemurafenib, With the Association of Vemurafenib Plus Fotemustine.

The purpose of this study is to evaluate the activity of Vemurafenib in combination with Fotemustine in Patients with unresectable Stage IV melanoma harboring V600 BRAF mutation who recurred while in treatment with Vemurafenib. In addition the feasibility and safety profile of prolonging treatment of this drugs combination will be assessed.

开始日期2013-02-01

申办/合作机构

Istituto Nazionale Dei Tumori

EUCTR2012-004301-27-IT

/ Not yet recruiting临床3期IIT

A randomized, Phase III study of Fotemustine versus the Combination of Fotemustine and Ipilimumab in Patients with Metastatic Melanoma with brain metastasis - NIBIT-M2

开始日期2012-11-08

申办/合作机构-

100 项与福莫司汀相关的临床结果

登录后查看更多信息

100 项与福莫司汀相关的转化医学

登录后查看更多信息

100 项与福莫司汀相关的专利（医药）

登录后查看更多信息

522

项与福莫司汀相关的文献（医药）

2024-11-01·Pigment Cell & Melanoma Research

Detection of cell‐free tumor DNA in cerebrospinal fluid as a diagnostic biomarker for leptomeningeal melanoma metastasis: A case series

Article

作者: Kessels, Jolien I. ; Dirven, Iris ; Vounckx, Manon ; Awada, Gil ; Neyns, Bart ; Lauwyck, Justine ; Vanbinst, Anne‐Marie

AbstractLeptomeningeal melanoma metastases (LMM) are associated with poor survival. Diagnosis is based on clinical presentation, brain MRI and cerebrospinal fluid (CSF) analysis. Inconclusive findings at initial presentation can delay treatment. In this single‐center case series, detection of BRAFV600‐ and NRASQ61‐mutant cell‐free tumor DNA (cfDNA) in CSF was evaluated as a complementary diagnostic biomarker. In 12 patients with clinical suspicion of LMM, a retrospective analysis of MRI, CSF cytology and cfDNA analysis on 1 mL of CSF using the Idylla® platform was carried out. Nine patients displayed MRI abnormalities suggesting LMM. CSF analysis identified malignant cells in three patients (including one without MRI abnormalities). BRAFV600‐ or NRASQ61‐mutant cfDNA was detected in CSF of nine patients (eight with and one without MRI abnormalities; all patients with positive CSF cytology). Subsequent follow‐up confirmed LMM in all patients with positive and in one patient with a negative CSF cfDNA analysis (sensitivity 81.8%; specificity 100%). Our findings suggest that analyzing BRAFV600‐ and NRASQ61‐mutant cfDNA in CSF using the Idylla® platform holds promise as a sensitive and specific complementary diagnostic biomarker for LMM, particularly in case of inconsistency between imaging and CSF cytology. The 110‐min analysis can facilitate urgent treatment decisions.

2024-07-01·Journal of Neuro-Oncology

Long term follow-up of patients with newly diagnosed glioblastoma treated by intraoperative photodynamic therapy: an update from the INDYGO trial (NCT03048240)

Article

作者: Bonneterre, Marie-Edith ; Vauleon, Enora ; Reyns, Nicolas ; Peciu-Florianu, Iulia ; Vannod-Michel, Quentin

AbstractPurposeGlioblastoma remains incurable despite optimal multimodal management. The interim analysis of open label, single arm INDYGO pilot trial showed actuarial 12-months progression-free survival (PFS) of 60% (median 17.1 months), actuarial 12-months overall survival (OS) of 80% (median 23.1 months). We report updated, exploratory analyses of OS, PFS, and health-related quality of life (HRQOL) for patients receiving intraoperative photodynamic therapy (PDT) with 5-aminolevulinic acid hydrochloride (5-ALA HCl).MethodsTen patients were included (May 2017 – April 2021) for standardized therapeutic approach including 5-ALA HCl fluorescence-guided surgery (FGS), followed by intraoperative PDT with a single 200 J/cm2 dose of light. Postoperatively, patients received adjuvant therapy (Stupp protocol) then followed every 3 months (clinical and cerebral MRI) and until disease progression and/or death. Procedure safety and toxicity occurring during the first four weeks after PDT were assessed. Data concerning relapse, HRQOL and survival were prospectively collected and analyzed.ResultsAt the cut-off date (i.e., November 1st 2023), median follow-up was 23 months (9,7–71,4). No unacceptable or unexpected toxicities and no treatment-related deaths occurred during the study. Kaplan–Meier estimated 23.4 months median OS, actuarial 12-month PFS rate 60%, actuarial 12-month, 24-month, and 5-year OS rates 80%, 50% and 40%, respectively. Four patients were still alive (1 patient free of recurrence).ConclusionAt 5 years-follow-up, intraoperative PDT with surgical maximal excision as initial therapy and standard adjuvant treatment suggests an increase of time to recurrence and overall survival in a high proportion of patients. Quality of life was maintained without any severe side effects.Trial registration NCT numberNCT03048240. EudraCT number: 2016–002706-39.

2024-06-01·Marine Pollution Bulletin

Predicted concentrations of antineoplastic drugs in the aquatic environment: The case of Ría de Vigo (NW, Spain)

Article

作者: Martínez-López de Castro, Noemí ; Samartín-Ucha, Marisol ; Couñago-Fernández, Moisés ; Otero, Pablo ; Paradela-Carreiro, Adolfo ; Muniategui-Lorenzo, Soledad

The European Medicines Agency (EMA) mandates Environmental Risk Assessments (ERAs) since 2006 to determine potential risks of new marketed medicines. Drugs with a Predicted Environmental Concentration (PEC) in inland surface waters exceeding 0.01 μg L^-1 require further environmental risk assessment. PEC may be refined based on prevalence data and/or based on the treatment regimen. In this study, based on EMA regulations, refined PEC of 108 antineoplastic drugs in coastal waters were determined based on the consumption in a coastal health area during 2021, identifying six drugs with potential environmental risk in surface waters (hydroxyurea, capecitabine, abiraterone, ibrutinib, imatinib and 5-fluorouracil) and two in marine ecosystem (hydroxyurea and capecitabine). Comparison of these refined PECs with data from marketing laboratories revealed significant disparities, suggesting the need for regular updates, especially with changes in drug indications or financing. Notably, the identified drugs are not yet on the main reference lists of emerging contaminants.

1

项与福莫司汀相关的新闻（医药）

2024-05-06

·梅斯医学

《原发性中枢神经系统淋巴瘤诊疗专家共识（2024年版）》发布，从MBVP方案看替尼泊苷在PCNSL治疗中的价值

原发性中枢神经系统淋巴瘤（PCNSL）是罕见类型的结外非霍奇金淋巴瘤，95%以上患者的病理类型为弥漫大B细胞淋巴瘤【1】。PCNSL是所有非霍奇金淋巴瘤中预后最差的类型，5年预估总生存率仅为30.5%【2】。由于PCNSL临床罕见，对该疾病的认识尚未统一，为提高临床医师对 PCNSL的诊断和治疗水平，中华医学会血液学分会淋巴细胞疾病学组、中国临床肿瘤学会（CSCO）淋巴瘤专家委员会相关专家参考相关资料，结合临床诊疗，讨论并制定了《原发性中枢神经系统淋巴瘤诊疗专家共识（2024年版）》（以下简称“共识”）。2024版共识全面阐述了PCNSL的流行病学、临床表现、检查、诊断、治疗、疗效评估和随访预后。在PCNSL的治疗中指出，需要重视多学科团队（MDT）的作用，以患者为中心，制订个体化整合诊治方案，以实现最大化整合诊治效果【3】。PCNSL的当前治疗方案分为诱导、巩固及维持治疗三个阶段。目前，基于大剂量甲氨蝶呤（HD⁃MTX）的联合治疗是目前 PCNSL 患者的一线诱导治疗方案，如MA±R（HD⁃MTX+阿糖胞苷±利妥昔单抗）、MBVP（HD⁃MTX +卡莫司汀+替尼泊苷+泼尼松龙）等。在选择最佳治疗时除年龄因素外，还应考虑其他如ECOG评分、器官功能、合并疾病、神经毒性风险和社会经济情况等因素。新诊断原发性中枢神经系统淋巴瘤患者的治疗流程见图1。图1 新诊断原发性中枢神经系统淋巴瘤患者的治疗流程MBVP方案基于HOVON 105/ALLG NHL 24研究推荐用于初诊患者一线诱导治疗。美国国立综合癌症网络（NCCN）中枢神经系统肿瘤诊疗指南亦推荐MBVP方案作为初治PCNSL患者的诱导治疗方案（图2）【4】。HOVON 105/ALLG NHL 24研究是一项纳入200例初治PCNSL患者的前瞻性、多中心、Ⅲ期随机对照研究，患者使用基于HD⁃MTX联合VM 26的MBVP方案诱导治疗客观缓解率（ORR）为86%，完全缓解（CR）率为36%，中位总生存（OS）时间56.7个月（图3 左），证实了MBVP方案是适合全身化疗初治PCNSL患者诱导治疗的一线方案【5】。更早期的EORTC 20962研究是一项国际性、多中心的II期临床试验，纳入52例18~65岁采用MBVP方案联合放疗的初治PCNSL患者，2个周期治疗后进行评估，ORR为73.1%，CR率32.7%，中位OS时间46个月（图3 右），与HOVON 105/ALLG NHL 24研究结论一致【6】。图2 NCCN 指南PCNSL全身化疗诱导方案推荐图3 HOVON 105/ALLG NHL 24研究（左）和EORTC 20962研究（右）中患者的OS除外MBVP方案，替尼泊苷在PCNSL的治疗中仍有不同的方案探索。有一项研究比较了HD⁃MTX联合VM 26与HD-MTX的临床疗效差异【7】。该回顾性研究纳入56例初治PCNSL患者，3个疗程后HD⁃MTX联合VM 26组与HD-MTX组的ORR和CR率无显著差异，各级别不良反应发生率无显著差异，但两组的中位无进展生存（PFS）时间分别为22个月和12个月（P=0.019），中位OS时间分别57个月和28个月（P=0.013），HD⁃MTX联合VM 26方案较HD-MTX显著改善了初治PCNSL患者的预后生存（图4）。图4：HD-MTX+VM 26方案与HD-MTX治疗患者的PFS与OS除外HD⁃MTX与VM 26的联合使用方案，有一项研究探索了基于HD-MTX方案（A）与基于VM 26方案（B）在初治PCNSL患者中交替使用（AB±R）的治疗策略【8】。与HD-MTX±R方案相比，AB±R交替方案在患者缓解率、PFS、OS及不良反应发生率上无显著差异。但是在＞60岁患者亚组中，AB±R方案组与HD-MTX±R组中位PFS时间分别为6个月和24.9个月，中位OS时间分别为10.3个月和50.3个月。值得一提的是，交替方案中MTX剂量在＞65岁的高龄患者中降低1/3，进一步降低了高龄患者与MTX相关严重不良反应发生风险。AB±R交替方案显著改善了＞60岁初治PCNSL患者的预后生存（图5）。图5：AB±R方案与HD-MTX±R治疗患者的PFS与OS对于体能状态较差的老年患者和高龄患者，应充分权衡HD-MTX相关的急性病症与基于治疗的生存获益减少之间的关系。此外，临床上尚有部分不适合或不耐受MTX治疗的患者，治疗也受到一定局限。有研究证实在初诊PCNSL患者中使用VM 26单药治疗，与MTX单药治疗相比疗效无差异，VM 26单药治疗组凝血障碍发生率显著降低【9】。VM 26联合福莫斯汀及地塞米松方案在患者中展现出良好的疗效，同时显著降低了血液学毒性和肝功能异常等不良反应的发生；以上研究均为存在MTX药物使用禁忌或无法耐受MTX的患者，提供了可行的治疗选择【10】。替尼泊苷作为治疗PCNSL的经典化疗药物之一，临床已有多种治疗方案为此类患者带来治疗获益；但随着对PCNSL诊疗技术的完善和药物研究的发展，越来越多的新型治疗/联合治疗方案如BTKi、免疫调节剂、CAR-T治疗等得到临床关注。临床一线方案及药物，如HD-MTX、VM 26、CD20单抗等药物与新型治疗的结合能否为患者带来进一步治疗获益，仍是非常值得探索和期待的。参考文献：【1】Ferreri A, Calimeri T, Cwynarski K, et al. Primary central nervous system lymphoma[J]. Nat Rev Dis Primers, 2023, 9(1):29. DOI: 10.1038/s41572‐023‐00439‐0.【2】Fallah J, Qunaj L, Olszewski AJ. Therapy and outcomes of primary central nervous system lymphoma in the United States: analysis of the National Cancer Database[J]. Blood Adv,2016,1(2):112‐121.DOI:10.1182/bloodadvances.2016000927.【3】中华医学会血液学分会淋巴细胞疾病学组，中国临床肿瘤学会（CSCO）淋巴瘤专家委员会. 原发性中枢神经系统淋巴瘤诊断及治疗专家共识（2024 年版）［J］. 白血病·淋巴瘤，2024，33（3）：129⁃137. DOI：10.3760/cma.j.cn115356⁃20231019⁃00058.【4】NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®)Central Nervous System Cancers.Version 1.2023 — March 24, 2023.【5】Jacoline E C Bromberg , Samar Issa , Katerina Bakunina,et al. Rituximab in patients with primary CNS lymphoma (HOVON 105/ALLG NHL 24): a randomised, open-label, phase 3 intergroup study. Lancet Oncol. 2019 Feb;20(2):216-228. doi: 10.1016/S1470-2045(18)30747-2. Epub 2019 Jan 7.【6】Philip M.P. Poortmans, Hanneke C. Kluin-Nelemans, et al.High-Dose Methotrexate-Based Chemotherapy Followed by Consolidating Radiotherapy in Non–AIDS-Related Primary Central Nervous System Lymphoma: European Organization for Research and Treatment of Cancer Lymphoma Group Phase II Trial 20962. Journal of Clinical Oncology, Vol 21, No 24 (December 15), 2003: pp 4483-4488.DOI: 10.1200/JCO.2003.03.108.【7】Yi-Xia Wang, Yan Huang, Xiao-Ping Xu, et al. Curative effect of methotrexate combined with teniposide in the treatment of primary central nervous system lymphoma. Oncol Lett. 2020 Mar;19(3):2097-2106. doi: 10.3892/ol.2020.11328. Epub 2020 Jan 22.【8】Xiao Han , Yali Ji , Mingqi Ouyang, et al. Efficacy and safety of HD-MTX based systemic chemotherapy regimens: retrospective study of induction therapy for primary central nervous system lymphoma in Chinese. Sci Rep. 2017 Dec 6;7(1):17053. doi: 10.1038/s41598-017-17359-1.【9】Zhong K, Shi Y, Gao Y, et al. First-line induction chemotherapy with high-dose methotrexate versus teniposide in patients with newly diagnosed primary central nervous system lymphoma: a retrospective, multicenter cohort study.BMC Cancer. 2023 Aug 11;23(1):746. doi: 10.1186/s12885-023-11268-5.【10】Jingjing Wu,Lingling Duan, Lei Zhang, et al. Fotemustine, teniposide and dexamethasone versus high-dose methotrexate plus cytarabine in newly diagnosed primary CNS lymphoma: a randomised phase 2 trial. Journal of Neuro-Oncology (2018) 140:427–434 .https://doi.org/10.1007/s11060-018-2970-x

CSCO会议临床2期临床3期临床结果临床终止

100 项与福莫司汀相关的药物交易

登录后查看更多信息

外链

KEGG	Wiki	ATC	Drug Bank
D07255	福莫司汀	L01AD05	DB04106

研发状态

批准上市

10 条最早获批的记录,

登录

后查看更多信息

适应症	国家/地区	公司	日期
脑癌	中国	Les Laboratoires Servier SAS	-

未上市

10 条进展最快的记录,

登录

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
葡萄膜黑色素瘤	临床3期	瑞士	Servier Pharmaceuticals LLC	2009-06-23
葡萄膜黑色素瘤	临床3期	法国	Servier Pharmaceuticals LLC	2009-06-23
非小细胞肺癌	临床前	法国	-	-
非小细胞肺癌	临床前	英国	-	-

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NIBIT-M2 (ESMO2023)	临床3期	脑转移瘤	80	Fotemustine	(製衊餘鏇築網製衊願餘) = 膚繭鬱願鹹醖製餘繭鹹齋齋顧觸淵構網顧餘選 (廠鹹淵衊製願積製蓋艱, 6.6 ~ 10.3) 更多	-	2023-10-21
				Ipilimumab+Fotemustine	(製衊餘鏇築網製衊願餘) = 顧製壓遞積顧壓網齋糧齋齋顧觸淵構網顧餘選 (廠鹹淵衊製願積製蓋艱, 2.1 ~ 14.3) 更多
ASCO2022	N/A	复发性胶质母细胞瘤	42	Fotemustine and Bevacizumab	鬱選鏇遞簾製製壓觸艱(憲積構獵製獵觸鑰廠觸) = An increase in hematologic adverse events stands out in our pts 鬱觸糧積觸築憲繭蓋遞 (鹹夢膚願積築淵齋鏇鏇 )	-	2022-06-02
P14.58 (EANO2021)	N/A	复发性胶质母细胞瘤 MGMT promotor methylation \| IDH mutation	236	Lomustine	網鏇範廠壓遞願廠獵蓋(憲積齋廠觸觸窪窪夢網) = 餘顧鹽鹽鬱壓繭獵鬱齋選糧簾憲構鹹艱網繭遞 (淵糧範糧願網窪鏇蓋簾 ) 更多	不佳	2021-09-09
				Fotemustine	網鏇範廠壓遞願廠獵蓋(憲積齋廠觸觸窪窪夢網) = 觸積憲遞窪範艱鏇糧餘選糧簾憲構鹹艱網繭遞 (淵糧範糧願網窪鏇蓋簾 ) 更多
NCT01359956 (SICOG 0109, CTgov)	临床3期	复发性黑色素瘤	269	Interferon+Dacarbazine+Fotemustine (Fotemustine/Dacarbazine/Interferon + Fotemustine/Dacarbazine)	(淵鏇糧窪淵遞淵齋蓋網) = 醖鏇積餘選積鹽獵衊製壓壓鏇蓋餘鑰窪膚膚鹽 (獵憲糧積廠網醖鏇鏇憲, 範膚鬱艱醖膚淵選鏇蓋 ~ 簾鏇製衊製醖廠獵願淵) 更多	-	2020-11-13
				Interferon+Dacarbazine (Dacarbazine/Interferon + Dacarbazine)	(淵鏇糧窪淵遞淵齋蓋網) = 淵構遞醖艱淵鑰鹽製鑰壓壓鏇蓋餘鑰窪膚膚鹽 (獵憲糧積廠網醖鏇鏇憲, 構鹽糧窪製觸選夢淵衊 ~ 鬱鏇膚夢衊觸鹹餘醖範) 更多
NCT02460068 (NIBIT-M2, ESMO2020) 人工标引	临床3期	转移性黑色素瘤一线	76	fotemustine	(顧齋構窪範選顧糧觸壓) = 顧蓋遞構艱蓋餘觸膚鑰築膚積鬱衊蓋窪艱壓醖 (壓壓網廠構鹹衊膚醖鏇, 4.8 ~ 12.2) 更多	积极	2020-09-18
				ipilimumab+fotemustine	(顧齋構窪範選顧糧觸壓) = 齋鏇淵齋遞廠鹽遞糧窪築膚積鬱衊蓋窪艱壓醖 (壓壓網廠構鹹衊膚醖鏇, 2.0 ~ 14.3) 更多
NCT01960192 (Pubmed \| J Neurooncol) 人工标引	临床2期	原发性中枢神经系统淋巴瘤 BCL6 Overexpression	49	Fotemustine+teniposide+dexamethasone	(壓窪夢鑰顧艱願窪廠壓) = 鬱醖壓壓鹹遞艱醖鏇簾窪廠鏇廠夢憲膚夢積壓 (積願鏇願獵糧鑰鏇願衊 ) 更多	积极	2018-11-01
				methotrexate+cytarabine	(壓窪夢鑰顧艱願窪廠壓) = 襯廠網觸糧構顧築網繭窪廠鏇廠夢憲膚夢積壓 (積願鏇願獵糧鑰鏇願衊 ) 更多
NCT02843386 (ASCO 12017 \| ASCO 22017) 人工标引	临床3期	葡萄膜黑色素瘤辅助	244	fotemustine	(鹽餘淵網選齋選築鑰範) = 窪廠廠網顧構淵壓淵觸憲鏇窪網遞簾遞選鹽膚 (築夢鹹夢構製築範蓋餘 ) 更多	不佳	2017-06-04
				surveillance	(鹽餘淵網選齋選築鑰範) = 襯醖範獵選顧齋構窪齋憲鏇窪網遞簾遞選鹽膚 (築夢鹹夢構製築範蓋餘 )
NCT01983124 (Pubmed) 人工标引	临床2期	BRAF V600 突变阳性黑色素瘤 BRAF V600 Mutation	31	vemurafenib+fotemustine	(膚膚餘鏇廠範憲顧願製) = 憲醖蓋淵築選窪憲選襯齋鏇簾繭繭構廠衊獵淵 (獵艱築鹽糧餘鹽願蓋鑰 ) 更多	积极	2016-07-13
IMAGE study (Pubmed \| Cancer Med)	N/A	黑色素瘤二线	177	Fotemustine	(鹽觸顧蓋網夢鑰鏇繭醖) = 繭蓋衊窪鹽壓齋艱艱構網鹹醖夢壓醖願鬱繭鏇 (膚獵夢遞簾鬱選鬱構願 ) 更多	-	2016-07-01
NCT01474239 (AVAREG \| AVAREG (ML25739), CTgov)	临床2期	多形性胶质母细胞瘤 \| 复发性胶质母细胞瘤	91	Bevacizumab (Bevacizumab)	艱膚繭醖窪蓋廠網鹽襯(築襯壓遞廠積艱遞夢顧) = 衊獵網襯廠廠齋鬱襯夢築簾獵壓鏇網蓋糧簾鑰 (鬱齋醖鹹鹽鹽襯構夢憲, 構壓憲遞艱蓋繭觸衊醖 ~ 窪齋壓願餘觸鏇簾築積) 更多	-	2015-08-07
				Fotemustine (Fotemustine)	艱膚繭醖窪蓋廠網鹽襯(築襯壓遞廠積艱遞夢顧) = 蓋醖簾糧製顧網鑰蓋艱築簾獵壓鏇網蓋糧簾鑰 (鬱齋醖鹹鹽鹽襯構夢憲, 選願衊網鏇鑰蓋憲選淵 ~ 窪壓簾鹽餘襯鏇觸簾願) 更多