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TREANDA(盐酸苯达莫司汀)

2010-12-16 11:47:31 作者：新特药房来源：中国新特药网天津分站浏览次数：3306 文字大小：【大】【中】【小】

简介： Treanda为美国Cephalon公司研制的新型抗肿瘤药物，化学名“苯达莫司汀”，属于烷化剂的一种。其抗肿瘤作用的发挥机制是破坏癌症细胞的DNA，从而导致细胞凋亡。慢性淋巴细胞性白血病（CLL）是危害人类健 ...

关键字：TREANDA(盐酸苯达莫司汀) BENDAMUSTINE HCL 非何杰金淋巴瘤浆细胞瘤乳腺癌

Treanda为美国Cephalon公司研制的新型抗肿瘤药物，化学名“苯达莫司汀”，属于烷化剂的一种。其抗肿瘤作用的发挥机制是破坏癌症细胞的DNA，从而导致细胞凋亡。
慢性淋巴细胞性白血病（CLL）是危害人类健康的恶性肿瘤之一，表现为由于淋巴细胞肿瘤样增殖，其特点为成熟形态的淋巴细胞在体内积聚使血液和骨髓中淋巴细胞增多，淋巴结、肝、脾肿大，最后累及淋巴系统以外的其他组织，CLL细胞呈单克隆性增殖，95％以上的慢淋为B细胞型，3－5％为T细胞型。
CLL在我国发生率较低，仅占慢性白血病的10％，日本和印度与我国相似，而欧美发病率很高，占慢性白血病的50％或更多，患者多为老年人，50岁以上占90％，男女之比为2∶1。
通过以上信息，我们也发现，尽管CLL非常罕见，但美国却是CLL相对高发的地区之一，Cephalon公司才致力于研究Treanda来攻克这一顽症。根据该公司提交的报告，美国每年大约新增15,000位CLL患者，严重影响了他们的健康。
Cephalon公司公布的一个试验数据标明，在有301位CLL患者参加的阳性对照试验中，Treanda组患者的有效率及存活期都优于已上市的化疗药物。
因此，美国FDA批准了该药的上市，并且，对了表彰Cephalon公司为攻克CLL这种罕见疾病所做出的贡献，FDA给了该公司一段时间的独占期。健康新闻3月20日报道：治疗慢性淋巴细胞性白血病（CLL）的新药Treanda通过了美国FDA的审核，即将在4月份上市。

英文名：Bendamustine

____品种概述____

盐酸苯达莫司汀最早于19世纪60年代初期由Ozegowski和其同事在德国耶拿的微生物试验协会研制。合成的目的是使一种烷基化氮芥（一种非功能烷化剂）连接一个嘌呤和氨基酸。新合成的化合物与苯丁酸氮芥相比主要的优点是它的水溶性。Anger et al.公开了苯达莫司汀对浆细胞瘤病人成功应用的最初临床结果。苯达莫司汀从1971年到1992年以Cytostasan的商品名由耶拿制药公司生产。从1993年后，这种细胞生长抑制剂被ribosepharm GmbH公司以Ribomustine的商品名上市销售。
最近，美国FDA于2008年3月21日批准Cephalon公司的盐酸苯达莫司汀（bendamustine，Treanda）用于慢性淋巴细胞性白血病（CLL）。CLL是1种恶性的淋巴细胞克隆性增殖性疾病，多见于老年人，平均发病年龄70岁，且男性多于女性。据美国癌症学会预计，2008年美国将有15000例CLL新发病例。分析师预计本品年销售峰值在3～5亿美元。此外，本品另一适应证－非霍奇金淋巴瘤目前正等待FDA批准。

____药理特点____

盐酸苯达莫司汀(Bendamustine Hydrochloride)是一种双功能基烷化剂，具有抗肿瘤和杀细胞作用。本品的抗肿瘤和杀细胞作用主要归功于DNA单链和双联通过烷化作用交联，这打乱了DNA的功能和DNA的合成，也会使DNA和蛋白之间，以及蛋白和蛋白之间产生交联，从而发挥抗肿瘤作用。本品作为单用或联合化疗,对何杰金氏淋巴瘤和非何杰金氏淋巴瘤的治疗反应率分别为61%～97%和41%～48%。

____临床应用____

本项目主要应用于单独或与其它抗肿瘤药物联合用药来治疗下列恶性肿瘤：何杰金病；非何杰金淋巴瘤；浆细胞瘤（多发性骨髓瘤）；慢性淋巴细胞白血病（CLL）；乳腺癌。

本品用于何杰金病、非何杰金淋巴瘤、多发性骨髓瘤、CLL和乳腺癌。其剂量血癌为50～60 mg/m2/d,3～5天或每3～4周为100～120 mg/m2 ；实体瘤每4 周为120～150 mg/m2 ,每日1 次,30～60 min 静脉滴注。盐酸苯达莫司汀作为单用或联合化疗,对何杰金病和非何杰金淋巴瘤的治疗反应率分别为61%～97%和41%～48 %。对多发性骨髓瘤病人,苯达莫司汀/泼尼松治疗的完全反应率较高(32 %) ,美法仑/ 泼尼松疗法反应更持久。在环磷酰胺、长春新碱、泼尼松治疗方案中,苯达莫司汀取代环磷酰胺,对发展中低度毒性非何杰金淋巴瘤有相似的反应率。在环磷酰胺、甲氨蝶呤、氟尿嘧啶治疗方案中,苯达莫司汀取代环磷酰胺,使转移性乳腺癌病人的缓解期从6.2 个月延长至15.2个月。

盐酸苯达莫司汀( bendamustine) 是双功能基烷化剂,体外对人卵巢癌和乳腺癌有细胞毒性,体外与环磷酰胺、美法仑(melphalan) 、卡莫司汀(carmustine)和顺铂有部分交叉耐受。对乳腺癌细胞系MCF7抑制细胞生长的IC50为138μmol/L,对顺铂抗药性卵巢癌细胞系A27802CP2 的IC50为157μmol/L ,对多柔比星抗药性乳腺癌细胞系MCF7AD 的IC50为187μmol/L。在等毒性浓度( IC50s)下,苯达莫司汀比美法仑、环磷酰胺或卡莫司汀引起更多的DNA 双螺旋断裂,比卡莫司汀或环磷酰胺作用更持久。体外引起浓度依赖性的B2慢性淋巴细胞白血病(B2CLL) 细胞凋亡,与氟达拉滨(fludarabine) 合用,在48 h 内凋亡率高1.4 倍。在Ⅰ期临床试验中,苯达莫司汀60～80 mg/m2每周1次,至8周,对顽固性实体瘤病人引起持久性的全淋巴细胞减少,主要为B细胞毒性。4周后,外周血B细胞、自然杀伤细胞和T 细胞分别下降90%,70%和60%以上。

Eisai Co., Ltd. (Headquarters: Tokyo, President & CEO: Haruo Naito, “Eisai”) today launched the anticancer agent TREAKISYM® Injection 100 mg (generic name: bendamustine hydrochloride) in Japan as a treatment for low-grade B-cell non-Hodgkin's lymphoma and mantle cell lymphoma. TREAKISYM® is the first anticancer agent for Eisai to launch in Japan, and although it is already available in the United States, its Japan launch marks the company's fully-fledged entry into the Japanese oncology market.

SymBio Pharmaceuticals Limited (Headquarters: Tokyo, President & CEO: Fuminori Yoshida, “SymBio”) received marketing approval for TREAKISYM® on October 27 of this year. The drug was today added to Japan’s National Health Insurance drug price list and will be marketed by Eisai in Japan based on a licensing agreement concluded between the two companies.

Eisai has established a Japan-based oncology promotion framework under which oncology information specialists have been assigned to each area and all of the approximately 1400 medical representatives (MRs) stationed around the country will provide information on anticancer therapies. The company will also work to ensure that a use results survey (all-case surveillance), a condition under which TREAKISYM® was approved, is carried out smoothly and promote the safe and efficacious use of the drug.

TREAKISYM® is a novel anticancer agent that exhibits nitrogen mustard-derived alkylating activity and antimetabolic-like activity. Clinical studies conducted in Japan showed that the agent offers excellent efficacy, has a high response rate, and significantly extends the duration of progression-free survival. More importantly, it is the first single agent for which patients with mantle cell lymphoma demonstrated a complete response. While the most frequently reported adverse reactions associated with TREAKISYM® include myelosuppression, nausea, vomiting, infection, vasculitis and angialgia, the agent maintains a manageable and highly tolerable safety profile. In Japan, SymBio is currently conducting Phase II clinical studies with the agent in relapsed and refractory intermediate- and high-grade B-cell non-Hodgkin’s lymphoma and untreated multiple myeloma as part of an indication expansion program.

Non-Hodgkin's lymphoma strikes an estimated 12,000 people in Japan each year, with the number of cases increasing in recent years. It is well known that many low-grade non-Hodgkin’s lymphoma patients are prone to repeated relapse after responding to initial treatment, making further treatment difficult despite extended overall survival. Mantle cell lymphoma is one of the rarest types of lymphoma. As most patients present with advanced stage disease, a common standard of care has yet to be established.

Eisai positions oncology as a therapeutic area of focus. Following the debut of its first anticancer agent TREAKISYM®, Eisai plans to continue to expand its portfolio of oncology products with agents such as eribulin (generic name), the company's first in-house developed anticancer agent currently under regulatory review for the treatment of breast cancer, thereby making contributions to addressing the diversified needs of cancer patients and their families.

[Please refer to the following notes for further information on bendamustine hydrochloride and a TREAKISYM® product outline and image]

Media Inquiries:
Public Relations Department,
Eisai Co., Ltd.
+81-(0)3-3817-5120

< Notes to editors >

1. About Bendamustine Hydrochloride
Bendamustine hydrochloride is an anticancer agent originally synthesized by German (formerly ‘East German’) pharmaceutical company Jenapharm and is marketed in Europe under the brand names Ribomustin® and Levact® as a treatment for non-Hodgkin's lymphoma, multiple myeloma and chronic lymphocytic leukemia. In the United States, the agent is marketed under the brand name TREANDA® as a treatment for chronic lymphocytic leukemia and relapsed indolent B-cell non-Hodgkin's lymphoma.
Eisai concluded an exclusive licensing agreement with SymBio in August 2008 concerning the joint development and marketing of bendamustine hydrochloride in Japan, which was followed by a subsequent agreement between the two companies in May 2009 concerning the development and marketing of the agent in Singapore and South Korea. The agent has been marketed in Singapore by Eisai’s Singapore subsidiary Eisai (Singapore) Pte. Ltd. since September of 2010 under the brand name of Symbenda® for the treatment of low-grade non-Hodgkin’s lymphoma and chronic lymphocytic leukemia.

2. TREAKISYM® Product Outline

Product Name:

TREAKISYM® Injection 100 mg

Generic Name:

Bendamustine Hydrochloride

Indications and Usage:

For the treatment of relapsed or refractory:

• Low-grade B-cell non-Hodgkin's lymphoma
• Mantle cell lymphoma

Dosage and Administration:

The usual adult dose of bendamustine hydrochloride is 120 mg/m² (body surface area) infused intravenously on Days 1 and 2 of repeated 21 day cycles. The dose may be reduced appropriately according to the condition of the patient.

National Health Insurance Drug Price Standard:

TREAKISYM® Injection 100 mg 92,356 yen per vial

3. Product Image