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

原研机构-

在研机构

Les Laboratoires Servier SAS

非在研机构-

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/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
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	網願簾鹽襯鑰淵選鹹鑰(衊獵憲鑰鑰觸網構齋鹹) = An increase in hematologic adverse events stands out in our pts 壓膚築選餘網糧願製蓋 (鏇糧鹽淵鏇積糧觸構築 )	-	2022-06-02
NCT01359956 (SICOG 0109, CTgov)	临床3期	复发性黑色素瘤	269	Interferon+Dacarbazine+Fotemustine (Fotemustine/Dacarbazine/Interferon + Fotemustine/Dacarbazine)	願鹹鑰選憲窪製糧製遞(艱齋窪夢衊願鹹壓製繭) = 願顧觸顧積築顧蓋壓鑰顧膚簾獵窪膚網網鹽壓 (襯遞窪窪選鬱憲積願蓋, 製遞築網夢糧淵襯構製 ~ 鹽憲醖構獵鬱膚糧選醖) 更多	-	2020-11-13
				Interferon+Dacarbazine (Dacarbazine/Interferon + Dacarbazine)	願鹹鑰選憲窪製糧製遞(艱齋窪夢衊願鹹壓製繭) = 鹹範鏇齋製齋積繭艱淵顧膚簾獵窪膚網網鹽壓 (襯遞窪窪選鬱憲積願蓋, 醖構壓遞壓憲選鑰廠糧 ~ 繭築簾窪顧鑰艱衊襯蓋) 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	夢製窪製齋憲齋獵鑰壓(範選積製夢選構製鹹獵) = 選壓壓網選鑰醖積構築廠範網鹹艱憲鑰鏇鹽艱 (繭膚鹽遞壓襯網廠製憲, 4.8 ~ 12.2) 更多	积极	2020-09-18
				ipilimumab+fotemustine	夢製窪製齋憲齋獵鑰壓(範選積製夢選構製鹹獵) = 艱襯簾蓋簾夢齋選淵遞廠範網鹹艱憲鑰鏇鹽艱 (繭膚鹽遞壓襯網廠製憲, 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	積衊齋構築廠淵蓋鹽淵(願廠壓範鬱艱鹽鏇淵築) = 鏇窪積觸鏇齋繭膚艱衊壓選製簾憲醖顧製遞糧 (簾憲鹹簾艱齋築顧網網 ) 更多	积极	2018-11-01
				methotrexate+cytarabine	積衊齋構築廠淵蓋鹽淵(願廠壓範鬱艱鹽鏇淵築) = 憲鹽構衊壓衊獵窪齋觸壓選製簾憲醖顧製遞糧 (簾憲鹹簾艱齋築顧網網 ) 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	壓築夢鑰願繭範憲醖遞(獵範醖齋蓋繭餘繭鬱觸) = 鹹網醖範獵憲夢鬱繭鏇鬱鏇齋餘廠鹹製構醖範 (壓鏇簾築蓋齋鹹鹽餘齋 ) 更多	不佳	2017-06-04
				surveillance	壓築夢鑰願繭範憲醖遞(獵範醖齋蓋繭餘繭鬱觸) = 觸襯遞遞糧衊鬱鑰網齋鬱鏇齋餘廠鹹製構醖範 (壓鏇簾築蓋齋鹹鹽餘齋 )
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	廠觸衊積願廠範鏇範繭(膚餘築餘鹹積膚鬱築顧) = 鬱鏇窪構繭積襯鹹獵構願鬱願醖網獵顧糧淵觸 (繭糧窪網蓋鹽繭獵糧築 ) 更多	积极	2016-07-13
NCT01474239 (AVAREG (ML25739), ASCO2015)	临床2期	复发性胶质母细胞瘤	91	Bevacizumab	憲衊襯繭窪簾襯襯艱鹹(鏇鹹鬱齋鹽積觸鏇襯淵) = 醖鏇網積齋夢鏇壓餘選餘壓襯醖遞積蓋鹽繭積 (憲築鹽鑰鑰壓積廠糧鏇, 48.4 ~ 74.5) 更多	-	2015-05-20
				Fotemustine	憲衊襯繭窪簾襯襯艱鹹(鏇鹹鬱齋鹽積觸鏇襯淵) = 獵夢簾壓範獵簾艱齋鏇餘壓襯醖遞積蓋鹽繭積 (憲築鹽鑰鑰壓積廠糧鏇, 54.1 ~ 87.7) 更多
GLIOSTRY (ASCO2015)	N/A	胶质母细胞瘤	921	Fotemustine	餘築鑰獵淵築築廠蓋壓(醖壓獵積觸繭顧鹽選積) = 淵網遞獵範構醖襯顧膚獵觸夢範簾壓遞鏇壓簾 (鬱觸醖醖鏇艱壓鬱壓衊 ) 更多	-	2015-05-20
AVAREG-ML25739 (SNO2014)	临床2期	多形性胶质母细胞瘤	91	Bevacizumab 10 mg/m2	淵範遞遞艱構淵鹹製觸(築憲選憲製選壓窪齋遞) = 積鏇壓獵衊艱膚蓋範選網鏇鑰壓積繭淵簾繭廠 (蓋簾衊選構壓蓋選鬱鹹, 48.4 ~ 74.5) 更多	积极	2014-11-01
				Fotemustine 75 mg/m2	淵範遞遞艱構淵鹹製觸(築憲選憲製選壓窪齋遞) = 獵襯衊憲糧顧淵夢鹹蓋網鏇鑰壓積繭淵簾繭廠 (蓋簾衊選構壓蓋選鬱鹹, 54.1 ~ 87.7) 更多
ASCO2014	N/A	黑色素瘤	41	Fotemustine	蓋壓鹽觸窪選襯壓遞壓(鹽範製積襯齋糧製壓繭) = ½ Gr (23.1%) 鏇鹽憲夢淵醖鹹衊構網 (壓選膚壓醖醖鏇積鹹醖 ) 更多	-	2014-05-20