福莫司汀(Fotemustine) - 药物靶点：DNA_在研适应症：黑色素瘤，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

肿瘤神经系统疾病皮肤和肌肉骨骼疾病

在研适应症

黑色素瘤脑癌

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初创企业

最高研发阶段批准上市

首次获批日期

新西兰 (1991-12-11),

黑色素瘤

最高研发阶段(中国)批准上市

特殊审评-

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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

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100 项与福莫司汀相关的转化医学

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100 项与福莫司汀相关的专利（医药）

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470

项与福莫司汀相关的文献（医药）

2024-03-27·BRIEFINGS IN BIOINFORMATICS

Metabolic models predict fotemustine and the combination of eflornithine/rifamycin and adapalene/cannabidiol for the treatment of gliomas

Article

作者: Heurtaux, Tony ; Pires Pacheco, Maria ; Sauter, Thomas ; Kishk, Ali

Abstract:

Gliomas are the most common type of malignant brain tumors, with glioblastoma multiforme (GBM) having a median survival of 15 months due to drug resistance and relapse. The treatment of gliomas relies on surgery, radiotherapy and chemotherapy. Only 12 anti-brain tumor chemotherapies (AntiBCs), mostly alkylating agents, have been approved so far. Glioma subtype–specific metabolic models were reconstructed to simulate metabolite exchanges, in silico knockouts and the prediction of drug and drug combinations for all three subtypes. The simulations were confronted with literature, high-throughput screenings (HTSs), xenograft and clinical trial data to validate the workflow and further prioritize the drug candidates. The three subtype models accurately displayed different degrees of dependencies toward glutamine and glutamate. Furthermore, 33 single drugs, mainly antimetabolites and TXNRD1-inhibitors, as well as 17 drug combinations were predicted as potential candidates for gliomas. Half of these drug candidates have been previously tested in HTSs. Half of the tested drug candidates reduce proliferation in cell lines and two-thirds in xenografts. Most combinations were predicted to be efficient for all three glioma types. However, eflornithine/rifamycin and cannabidiol/adapalene were predicted specifically for GBM and low-grade glioma, respectively. Most drug candidates had comparable efficiency in preclinical tests, cerebrospinal fluid bioavailability and mode-of-action to AntiBCs. However, fotemustine and valganciclovir alone and eflornithine and celecoxib in combination with AntiBCs improved the survival compared to AntiBCs in two-arms, phase I/II and higher glioma clinical trials. Our work highlights the potential of metabolic modeling in advancing glioma drug discovery, which accurately predicted metabolic vulnerabilities, repurposable drugs and combinations for the glioma subtypes.

2024-03-01·European journal of cancer (Oxford, England : 1990)

Nivolumab plus ipilimumab in melanoma patients with asymptomatic brain metastases: 7-year outcomes and quality of life from the multicenter phase III NIBIT-M2 trial

Article

作者: Quaglino, Pietro ; Simonetti, Elena ; Chiarion-Sileni, Vanna ; Ferrucci, Pier Francesco ; Camerini, Roberto ; Maio, Michele ; Covre, Alessia ; Calabrò, Luana ; Giannarelli, Diana ; Del Vecchio, Michele ; Amato, Giovanni ; Guida, Michele ; Di Giacomo, Anna Maria ; Santangelo, Federica ; Marchetti, Paolo ; Guidoboni, Massimo ; Mandalà, Mario ; Valente, Monica

BACKGROUND:

The primary analysis of the phase III NIBIT-M2 study showed a 41% 4-year overall survival (OS) of melanoma patients with asymptomatic brain metastases treated with ipilimumab plus nivolumab.

METHODS:

Here, we report the 7-year efficacy outcomes and the Health-Related Quality of Life (HRQoL) analyses of the NIBIT-M2 study.

RESULTS:

As of May 1, 2023, at a median follow-up of 67 months (mo), the median OS was 8.5 (95% CI: 6.6-10.3), 8.2 (95% CI: 2.1-14.3) and 29.2 (95% CI: 0-69.9) mo for the fotemustine (F) Arm A, ipilimumab plus fotemustine Arm B, and ipilimumab plus nivolumab Arm C, respectively. The 7-year OS rate was 10.0% (95% CI: 0-22.5) in Arm A, 10.3% (95% CI: 0-22.6) in Arm B, and 42.8% (95% CI: 23.4-62.2) in Arm C. HRQoL was preserved in all treatment arms. Most functional scales evaluated from baseline to W12 were preserved, with a lower mean score decrease for EORTC Quality of Life Questionnaire (QLQ)-C30 and an increase for EORTC QLQ-Brain neoplasm (BN20) in patients receiving ipilimumab plus nivolumab.

CONCLUSIONS:

With the longest follow-up available to date in melanoma patients with asymptomatic brain metastases, the NIBIT-M2 study continues to show persistent therapeutic efficacy of I ipilimumab plus nivolumab while preserving HRQoL.

2023-11-02·Immunopharmacology and immunotoxicology

Efficacy and safety of the combined use of ipilimumab and nivolumab for melanoma patients with brain metastases: a systematic review and meta-analysis

Review

作者: Yang, Yuyan ; Su, Mengmeng ; Wang, Peng

CONTEXT:

Immune checkpoint inhibitors have advanced immunotherapy for melanoma patients.Objective: This study evaluates efficacy and safety of ipilimumab and nivolumab combination (IN) for melanoma brain metastases (MBM) patients.

MATERIALS AND METHODS:

Literature search was conducted in electronic databases and studies were included if they reported efficacy and safety of IN in MBM patients or prognostic information related to brain metastases. Outcomes evaluated were objective response rate (ORR), complete remission/stable disease/progressive disease rates, progression-free survival (PFS), overall survival (OS), incidence rates of adverse events, and hazard ratios of disease progression or mortality between IN-treated patients with and without brain metastasis.

RESULTS:

Intracranial ORR was higher in IN-treated MBM patients than with control therapies (nivolumab or ipilimumab plus fotemustine). IN treatment led to longer PFS and OS in than control treatments. Five-year OS of IN-treated MBM patients was up to 51% compared to 34% for nivolumab. Outcomes were better for treatment naïve and asymptomatic patients. Whereas many studies reported significantly higher mortality or progression risk with IN treatment in MBM patients compared to non-MBM melanoma patients, many others did not find this risk significant. Incidence of grade 3/4 adverse events in IN-treated MBM patients was: diarrhea or colitis (16%), hepatitis (15%), rash (8%), increased alanine transaminase (8%), increased aspartate aminotransferase (7%), increased lipase (6%), increased amylase (4%), fatigue (3%), hypophysitis (2%), pneumonitis (2%), headache (2%), nausea or vomiting (1%), and neutropenia (1%).

CONCLUSION:

IN is an efficacious and safer treatment option for MBM patients, especially for asymptomatic and treatment naïve patients.

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.libproxy1.nus.edu.sg/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

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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,

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适应症	国家/地区	公司	日期
黑色素瘤	新西兰	-	1991-12-11
脑癌	中国	Les Laboratoires Servier SAS	-

未上市

10 条进展最快的记录,

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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	法国	Servier Pharmaceuticals LLC初创企业	2009-06-23
葡萄膜黑色素瘤	临床3期	瑞士	Servier Pharmaceuticals LLC初创企业	2009-06-23
非小细胞肺癌	临床2期	法国	-	-
非小细胞肺癌	临床2期	英国	-	-

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临床结果

适应症

分期

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


ASCO2022	N/A	复发性胶质母细胞瘤	42	Fotemustine and Bevacizumab	顧願鬱鬱願顧鏇壓築餘(積襯鑰餘襯憲齋觸範遞) = An increase in hematologic adverse events stands out in our pts 襯鹹廠構範艱醖範蓋鹽 (糧艱壓構鹽糧鹽遞淵鏇 )	-	2022-06-02
NCT02460068 (NIBIT-M2, ESMO2020) 人工标引	临床3期	转移性黑色素瘤一线	76	fotemustine	膚襯糧鏇鹽夢壓鬱淵窪(繭觸醖餘獵餘網鹽窪蓋) = 獵艱艱選壓糧獵構齋醖鏇膚繭衊簾遞糧選淵積 (願糧鬱糧獵窪淵製觸蓋, 4.8 ~ 12.2) 更多	积极	2020-09-18
				ipilimumab+fotemustine	膚襯糧鏇鹽夢壓鬱淵窪(繭觸醖餘獵餘網鹽窪蓋) = 鹽鏇繭壓蓋積糧艱遞網鏇膚繭衊簾遞糧選淵積 (願糧鬱糧獵窪淵製觸蓋, 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	壓鹽選夢鬱鏇鏇鹹構艱(積餘鹽蓋鹹襯遞廠遞鹽) = 鏇廠膚鬱廠網範製選鹽憲膚範觸蓋製膚鹹築鑰 (糧範夢淵簾艱簾網鏇膚 ) 更多	积极	2018-11-01
				methotrexate+cytarabine	壓鹽選夢鬱鏇鏇鹹構艱(積餘鹽蓋鹹襯遞廠遞鹽) = 顧繭餘齋顧蓋鏇願鬱積憲膚範觸蓋製膚鹹築鑰 (糧範夢淵簾艱簾網鏇膚 ) 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	夢醖醖夢顧鏇構網廠築(壓齋夢襯襯鏇餘餘憲簾) = 餘構願遞獵艱蓋襯襯壓鏇齋鬱獵壓窪觸築鬱築 (構廠淵膚願鬱願鬱襯顧 ) 更多	不佳	2017-06-04
				surveillance	夢醖醖夢顧鏇構網廠築(壓齋夢襯襯鏇餘餘憲簾) = 憲夢繭鹹鏇遞襯繭鏇餘鏇齋鬱獵壓窪觸築鬱築 (構廠淵膚願鬱願鬱襯顧 )
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	壓艱願窪膚願構積糧壓(鏇膚糧簾鬱艱夢齋範鏇) = 範齋鹹壓窪製醖獵構製鏇醖醖積繭襯鹽醖鏇觸 (淵鬱衊餘遞積積構繭觸 ) 更多	积极	2016-07-13
GLIOSTRY (ASCO2015)	N/A	胶质母细胞瘤	921	Fotemustine	窪鏇齋網衊顧鬱積鬱製(憲壓簾選網遞壓憲網構) = 獵選選壓廠鬱蓋願醖艱繭鏇窪鬱遞艱襯鏇鹽鹽 (繭鏇壓襯願鹽遞積鏇餘 ) 更多	-	2015-05-20
NCT01474239 (AVAREG (ML25739), ASCO2015)	临床2期	复发性胶质母细胞瘤	91	Bevacizumab	艱淵獵艱糧遞鏇壓積網(艱衊製積鏇夢糧獵廠淵) = 繭衊夢顧鬱網齋蓋獵餘鏇顧範淵製廠壓膚構構 (憲糧衊鬱齋顧餘蓋簾艱, 48.4 ~ 74.5) 更多	-	2015-05-20
				Fotemustine	艱淵獵艱糧遞鏇壓積網(艱衊製積鏇夢糧獵廠淵) = 觸鑰願鹹憲淵觸遞鹹獵鏇顧範淵製廠壓膚構構 (憲糧衊鬱齋顧餘蓋簾艱, 54.1 ~ 87.7) 更多
EUCTR2011-001363-46-IT (AVAREG-ML25739, SNO2014)	临床2期	多形性胶质母细胞瘤	91	Bevacizumab 10 mg/m2	積範鹹鹽鹽廠艱鹹鹹糧(顧蓋齋襯選壓艱選壓簾) = 觸鏇窪獵網廠製鏇築衊醖網鹽窪蓋網膚淵顧獵 (膚蓋淵繭襯餘淵衊鏇製, 48.4 ~ 74.5) 更多	积极	2014-11-01
				Fotemustine 75 mg/m2	積範鹹鹽鹽廠艱鹹鹹糧(顧蓋齋襯選壓艱選壓簾) = 膚遞糧鑰鹽鏇廠蓋衊醖醖網鹽窪蓋網膚淵顧獵 (膚蓋淵繭襯餘淵衊鏇製, 54.1 ~ 87.7) 更多
GEINOFOTE (ASCO2014)	N/A	高级别胶质瘤	114	fotemustine (FT) (Addeo schedule)	築觸選繭壓膚鑰壓夢蓋(遞艱淵製蓋夢壓鑰廠觸) = 衊網鑰製選廠構廠壓鹽醖鹹糧壓衊鬱鏇鹽築鏇 (襯蓋願醖鹽觸窪範醖鏇 ) 更多	-	2014-05-20
				fotemustine (FT) (Others schedule)	築觸選繭壓膚鑰壓夢蓋(遞艱淵製蓋夢壓鑰廠觸) = 窪網觸淵憲壓齋選蓋齋醖鹹糧壓衊鬱鏇鹽築鏇 (襯蓋願醖鹽觸窪範醖鏇 ) 更多
ASCO2014	N/A	黑色素瘤	41	Fotemustine	廠衊築艱齋壓蓋窪鑰網(鬱膚鬱艱艱遞網範糧醖) = ½ Gr (23.1%) 膚鹽夢獵夢鬱糧鬱製簾 (窪鏇餘衊構積壓鏇壓淵 ) 更多	-	2014-05-20