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。
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]
Public Relations Department,
Eisai Co., Ltd.
< 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
TREAKISYM® Injection 100 mg
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
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 ...