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英文药名：Beleodaq(belinostat injection)
中文药名：注射用贝利司他
生产厂家：Spectrum药业
药品介绍
近日，美国FDA通过加速批准通道批准了Spectrum的HDAC抑制剂belinostat（商品名：Beleodaq）上市，治疗一种复发或难治性的罕见淋巴瘤—外周T细胞淋巴瘤（PTCL）。根据一项有120名复发或难治性PTCL患者参与的多中心，单臂的三期临床研究（BELIEF实验），每天静脉注射一次Beleodaq（1000毫克/平米）连续5天，有25.8%的患者表现应答，其中有10.8%的完全应答和15%的部分应答，达到一级临床终点。患者的平均应答时间为8.4个月。患者常见的副作用包括发热、贫血、恶心、呕吐和疲劳等。
批准日期：2014年7月3日；公司: Spectrum药业公司
BELEODAQ®(belinostat)注射用，为静脉给药
美国初始批准：2014
适应证和用途
Beleodaq是一种组蛋白去乙酰化酶抑制剂[histone deacetylase inhibitor]适用为有复发或难治周边T细胞淋巴瘤(PTCL)患者的治疗，这个适应证是在根据肿瘤反应率和反应时间在加速批准下批准的。尚未确定改善生存或疾病相关症状。继续批准这个适应证可能取决于在验证性试验中核实和描述临床获益。
剂量和给药方法
⑴Beleodaq的推荐剂量是在21天疗程的第1-5天每天1次1,000mg/m2通过静脉历时30分钟输注给药。疗程可重复直至疾病进展或不可接受的毒性。
⑵为处理不良反应可能需要终止治疗或中断有或无剂量减少25%。
剂型和规格
为注射：500mg ，冻干粉在为重建的一次性使用小瓶。
禁忌证
无
警告和注意事项
⑴血小板减少，白细胞减少(中性粒细胞减少和淋巴细胞减少)，和贫血：监视血细胞计数和对血液学毒性调整剂量。
⑵感染：严重和致命性感染(如，肺炎和败血症)。
⑶肝毒性：Beleodaq可能致肝毒性和肝功能测试异常。监视肝功能测试和omit或调整剂量 for 肝毒性.
⑷肿瘤溶解综合证：监视有晚期疾病和/或高肿瘤负荷患者和采取适当措施。
⑸胚胎-胎儿毒性：当给予一位妊娠妇女Beleodaq可能致胎儿危害。忠告妇女对胎儿潜在危害和当接受Beleodaq时避免妊娠。
不良反应
最常见不良反应(>25%)是恶心，疲劳，发热，贫血，和呕吐。
特殊人群中使用
哺乳母亲：当正在用治疗时Beleodaq应忠告妇女不要哺乳。
BELEODAQ™ (belinostat) for injection
a pan HDAC inhibitor
BELEODAQ (belinostat) injection, powder, lyophilized, for solution
[Spectrum Pharmaceuticals, Inc.]
Target Indications
Peripheral T-Cell Lymphoma (PTCL)
Carcinoma of Unknown Primary (CUP)
Non-Small Cell Lung Cancer (NSCLC)
Other solid tumors and hematological malignancies
Route of Administration
IV
Mode of Action
BELEODAQ (PXD 101) is a pan HDAC inhibitor in late stage clinical development with more than 1,000+ patients treated to date. BELEODAQ is believed to inhibit enzymatic activity of class 1 and class 2 HDACs. BELEODAQ is also believed to increase in acetylation of both histone and histone proteins, resulting in cell cycle arrest, apoptosis and a decrease in cell proliferation.
Status
Currently in a Pivotal study in PTCL
In clinical trials, BELEODAQ has shown that it may be well-tolerated, which allows for combination with traditional chemotherapy without causing excessive bone marrow toxicity. In pre-clinical studies BELEODAQ has shown to be active against multiple cancers by inhibiting cell proliferation (inhibiting cancer growth) and inducing programed cell death ("apoptosis") in tumor cells (the tumor cells are forced to self-destruct).
BELEODAQ has been eva luated in a number of Phase 1 and 2 clinical trials in hematological cancers and solid tumors. Data from these trials have provided for the anti-tumor effect of BELEODAQ as monotherapy in peripheral T-cell lymphomas (PTCL) and in combination with other anti-cancer drugs for the treatment of multiple types of cancer including CUP and non-small cell lung cancer (NSCLC).
To date clincal trials suggest BELEODAQ is well tolerated at full dose. The most frequent adverse events of any grade and irrespective of study design have been nausea, fatigue and vomiting. As such, it is being investigated in high doses not only alone, but also in drug combinations. In preclinical tumor models, BELEODAQ is active in cancer cells that have become resistant to existing chemotherapies. BELEODAQ could add substantial treatment value to several important drug combinations.
The FDA granted approval of BELEODAQ for relapsed or refractory PTCL on July 3, 2014.
Continued support from the National Cancer Institute (NCI) has helped build a comprehensive program which has identified the optimal development route for BELEODAQ. The development of BELEODAQ is planned in collaboration with the NCI, and all trials are born from laboratory data showing the most favorable methods of use and combinations.
Based on available data so far, Spectrum believes that BELEODAQ has the potential to become the "best in class" pan HDAC inhibitor. The efficacy of BELEODAQ noted in ongoing clinical trials is likely to be linked to the high blood concentrations of drug achieved using intravenous ("IV") dosing. This high blood concentration may not be attainable for other pan HDAC inhibitors. BELEODAQ has also exhibited a favourable safety profile.
美国FDA批准Spectrum的HDAC抑制剂belinostat（Beleodaq）上市，治疗外周T细胞淋巴瘤（PTCL）
2014年7月3日，美国FDA批准Beleodaq(belinostat)用于外周T细胞淋巴瘤(PTCL)患者治疗，PTCL是一种罕见并快速增长的非霍奇金淋巴瘤(NHL)。这次的批准是在FDA加速批准程序下完成。
PTCL由不同组的疾病组成，这类疾病的淋巴结发生癌变。2014年，美国国家癌症研究所预测70800名美国人将被确诊为NHL，而有18990人会死亡。在北美，PTCL占NHLs的比例大约在10%到15%。
Beleodaq通过阻止有助于T细胞（一种免疫细胞）发生癌变的酶起作用。这款药物适用于治疗后（复发性）疾病又卷土重来或对以前治疗无效（难治性）的患者。
“这是自2009年以来获批用于外周T细胞淋巴瘤治疗的第三款药物，”FDA药品评价与研究中心血液及肿瘤产品办公室主任、医学博士Pazdur说。“今天的批准为患有这种严重及危及生命疾病的患者增加了一种可供使用的治疗选择。”
2009年，FDA加速批准普拉曲沙（Folotyn）用于复发或难治性PTCL患者，2011年批准罗咪酯肽（Istodax）用于之前至少接受过一种治疗的PTCL患者。
Beleodaq的安全性及有效性在一项由129名复发或难治性PTCL受试者参与的临床研究中得到评价。所有受试者均以Beleodaq治疗，直到他们的疾病发生恶化或副作用变得不可接受。结果显示，25.8%受试者的癌症在治疗后消失（完全缓解）或缩小（部分缓解）。Beleodaq治疗受试者最常见副作用有恶心、疲劳、发烧(发热)、低红细胞水平(贫血)和呕吐。
Beleodaq与普拉曲沙由Spectrum制药上市销售。Istodax由塞尔基因上市销售。
http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206256lbl.pdf |
