当前位置：药品说明书与价格首页 >> 抗肿瘤药 >> 新药推荐 >> Adcetris注射液(brentuximab vedotin)

Adcetris注射液(brentuximab vedotin)

2011-11-28 19:35:03 作者：新特药房来源：中国新特药网天津分站浏览次数：1876 文字大小：【大】【中】【小】

简介： 制造商：西雅图遗传学公司类药物：CD30 +定向抗体药物共轭。活性成分（S）：Brentuximab vedotin 50mg/vial;四，重组后的输液粉，不含防腐剂。指示（S）：霍奇金淋巴瘤（HL）治疗失败后的自体干细 ...

关键字：Adcetris（brentuximab vedotin注射液）两种类的淋巴瘤新药上市 FDA批准

制造商：
西雅图遗传学公司

类药物：
CD30 +定向抗体药物共轭。

活性成分（S）：
Brentuximab vedotin 50mg/vial;四，重组后的输液粉，不含防腐剂。

指示（S）：
霍奇金淋巴瘤（HL）治疗失败后的自体干细胞移植（ASCT）或至少前两个多代理的病人谁不ASCT候选人的化疗方案失败后。系统性间变性大细胞淋巴瘤（sALCL）至少有一个事先的多代理化疗失败后的处理。

药理：
Brentuximab vedotin是一种抗体药物共轭器（ADC）。抗体是针对CD30的嵌合IgG1的。小分子，甲基auristatin E（MMAE），微管破坏剂，是通过一个连接器的抗体共价连接。非临床数据表明，brentuximab vedotin的抗癌活性是由于ADC的CD30 -表达细胞结合，内化的ADC - CD30复杂，MMAE通过释放蛋白水解裂解。 MMAE以微管蛋白结合，干扰细胞内的微管网络，随后诱导细胞周期阻滞和细胞凋亡。

临床试验：
单手臂，多中心试验，涉及102例患者治疗HL的brentuximab vedotin疗效评价。在试验中，患者治疗brentuximab vedotin 1.8mg/kg IV超过30分钟，每3周。这项研究的疗效终点是总反应率（ORR =完全缓解[CR +部分缓解[PR]）和响应时间，通过临床和影像学措施。端点，73％的患者取得了一个完整的治疗或部分缓解，为6.7个月，平均回应。

单一型臂，多涉及58名患者的试验中brentuximab vedotin在治疗复发sALCL的疗效进行了评估。在试验中，患者治疗brentuximab vedotin 1.8mg/kg IV超过30分钟，每3周。这项研究的疗效终点为ORR和持续时间响应。接收brentuximab sALCL vedotin患者，86％经历了一个完整的或部分的反应和回应平均为12.6个月。

法律分类：
接收

成人：
静脉滴注超过30分钟给予。 1.8mg/kg，每3周;继续下去，直到16个周期，疾病进展或不可接受的毒性最大。周围神经病变：如果等级2 / 3：扣留，直到解决≤1级，然后重新启动与1.2mg/kg;如果4级：停止治疗。嗜中性白血球减少症：3 / 4级：扣留，直到解决≤2级;可以考虑生长因子的支持;经常四级：停止或考虑减少剂量至1.2mg/kg。

儿童：
不成立的。

警告/注意事项：
监测神经病和延迟，更改或终止相应的剂量。监测输注相关反应;永久停止治疗，如果过敏反应发生。监视器CBCS之前，各剂量，并经常为3或4级中性粒细胞减少;如果开发，推迟，减少或停止剂量。在快速增殖的肿瘤/高肿瘤负担的患者肿瘤溶解综合征的风险增加;密切监测。怀孕（目录四）避免。哺乳的母亲：不推荐。

相互作用（S）：
Potentiated由强CYP3A4抑制剂（如酮康唑）;监测。拮抗强效CYP3A4的诱导剂（如利福平）。

不良反应（S）：
中性粒细胞减少，周边感觉神经病变，疲劳，胃肠不适，贫血，上呼吸道感染，发热，皮疹，血小板减少，咳嗽，输液反应，Stevens - Johnson综合征（终止如果发生），PML的可能。

如何提供：
单用小瓶- 1

最后更新：
2011年11月23日

FDA批准Adcetris用于治疗两种类型的淋巴瘤

美国食品和药物管理局2011年8月19日批准brentuximab vedotin（Adcetris）用于治疗霍奇金淋巴瘤以及复发性间变性大细胞淋巴瘤(ALCL)。
淋巴瘤是淋巴系统的癌症。 Adcetris是新型靶向抗体-药物偶联物，能使药物直接作用于淋巴瘤细胞上的靶点CD30。
Adcetris用于那些在接受自体干细胞移植后，或那些不能接受移植手术而在之前接受化疗后病情恶化的HL患者。自体造血干细胞移植是一个利用患者自身的骨髓用以修复高剂量化疗后受损的骨髓的过程。 Adcetris也可用于在一个前化疗治疗后病情恶化的ALCL患者。
“早期临床数据表明，服用Adcetris用于治疗霍奇金淋巴瘤和系统性间变性淋巴瘤的患者对该药物产生显著反应，”， FDA药物评价和研究中心肿瘤药物产品办公室主任医学博士Richard Pazdur说。
根据国家癌症研究所（NCI）研究，HL常见的症状包括淋巴结肿大，脾，发热，消瘦，乏力，盗汗。据NCI估计，2011年美国将诊断出8830例新的HL病例，其中约1300人将死于这种疾病。
国家癌症研究所研究发现系统性ALCL是一种罕见的恶性肿瘤（非霍奇金淋巴瘤），可能会出现在身体的几个部分，包括淋巴结，皮肤，骨骼，软组织，肺或肝。
Adcetris是自1977年以来第一个FDA批准的治疗HL的新药，也是第一种专门针对ALCL的药物。
通过1项单一的涉及102例患者的临床试验对Adcetri治疗HL的有效性进行了评估。在单组试验中，患者只服用Adcetris。这项研究的主要终点是客观缓解率，即经历治疗后癌症症状完全消失或部分减缓的患者比例。73%的患者得到了完全治愈或部分缓解。平均而言，这些患者对治疗产生反应时间为6.7个月。
通过1项单一的涉及58例患者的临床试验对Adcetri治疗AHCL的有效性进行了评估。在单组试验中，患者只接受Adcetris治疗。与HL试验类似，试验的主要终点是客观缓解率。接收Adcetris治疗的ALCL患者，86%得到了完全治愈或部分缓解，平均周期为12.6个月。
Adcetris最常见的副作用有：减少起对抗感染作用的白血细胞（嗜中性白血球减少症），神经损伤（周围感觉神经病变），疲劳，恶心，贫血，上呼吸道感染，腹泻，发烧，咳嗽，呕吐，和血小板水平低下（血小板减少症）。
孕妇应注意Adcetris可能对未出生的婴儿造成损害。

ADCETRIS

Manufacturer:

Seattle Genetics, Inc.

Pharmacological Class:

CD30-directed antibody-drug conjugate.

Active Ingredient(s):

Brentuximab vedotin 50mg/vial; powder for IV infusion after reconstitution; preservative-free.

Indication(s):

Treatment of Hodgkin lymphoma (HL) after failure of autologous stem cell transplant (ASCT) or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not ASCT candidates. Treatment of systemic anaplastic large cell lymphoma (sALCL) after failure of at least one prior multi-agent chemotherapy regimen.

Pharmacology:

Brentuximab vedotin is an antibody-drug conjugate (ADC). The antibody is a chimeric IgG1 directed against CD30. The small molecule, monomethyl auristatin E (MMAE), is a microtubule disrupting agent and is covalently attached to the antibody via a linker. Nonclinical data suggest that the anticancer activity of brentuximab vedotin is due to the binding of the ADC to CD30-expressing cells, followed by internalization of the ADC-CD30 complex, and the release of MMAE via proteolytic cleavage. Binding of MMAE to tubulin disrupts the microtubule network within the cell, subsequently inducing cell cycle arrest and apoptotic death of the cells.

Clinical Trials:

The efficacy of brentuximab vedotin in treating HL was evaluated in a single-arm, multicenter trial involving 102 patients. In the trial, patients were treated with brentuximab vedotin 1.8mg/kg IV over 30 minutes every 3 weeks. The study’s efficacy endpoint was overall response rate (ORR = complete remission [CR] + partial remission [PR]) and duration of response as defined by clinical and radiographic measures. At endpoint, 73% of patients achieved either a complete or partial response to the treatment and responded on average for 6.7 months.

The efficacy of brentuximab vedotin in treating relapsed sALCL was evaluated in a single-arm, multicenter trial involving 58 patients. In the trial, patients were treated with brentuximab vedotin 1.8mg/kg IV over 30 minutes every 3 weeks. The study’s efficacy endpoint was also ORR and duration of response. Of the patients receiving brentuximab vedotin for sALCL, 86% experienced either a complete or partial response and responded on average for 12.6 months.

Legal Classification:

Adults:

Give by IV infusion over 30 minutes. 1.8mg/kg every 3 weeks; continue until a max of 16 cycles, disease progression or unacceptable toxicity. Peripheral neuropathy: if Grade 2/3: withhold until resolve to ≤Grade 1, then restart with 1.2mg/kg; if Grade 4: discontinue therapy. Neutropenia: Grade 3/4: withhold until resolve to ≤Grade 2; may consider growth factor support; recurrent Grade 4: discontinue or consider reducing dose to 1.2mg/kg.

Children:

Not established.

Warnings/Precautions:

Monitor for neuropathy and delay, change, or discontinue dose accordingly. Monitor for infusion-related reactions; permanently discontinue and treat if anaphylaxis occurs. Monitor CBCs prior to each dose and frequently for Grade 3 or 4 neutropenia; if develops, delay, reduce or discontinue dose. Increased risk of tumor lysis syndrome in rapidly proliferating tumor/high tumor burden patients; monitor closely. Pregnancy (Cat. D); avoid. Nursing mothers: not recommended.

Interaction(s):

Potentiated by strong CYP3A4 inhibitors (eg, ketoconazole); monitor. Antagonized by potent CYP3A4 inducers (eg, rifampin).

Adverse Reaction(s):

Neutropenia, peripheral sensory neuropathy, fatigue, GI upset, anemia, upper respiratory tract infection, pyrexia, rash, thrombocytopenia, cough; infusion reactions, Stevens-Johnson syndrome (discontinue if occurs), possible PML.

How Supplied:

Single-use vial—1

Adcetris Approval History
FDA approved: Yes (First approved August 19th, 2011)

Brand name: Adcetris

Generic name: brentuximab vedotin

Company: Seattle Genetics, Inc.

Treatment for: Lymphoma, Hodgkin\'s Lymphoma

Adcetris (brentuximab vedotin) is a CD30-directed antibody-drug conjugate (ADC) indicated for the treatment of relapsed or refractory Hodgkin lymphoma and systemic anaplastic large cell lymphoma (ALCL).

购买可以联系http://www.131.org.cn

FDA approved Adcetris (brentuximab vedotin; Seattle Genetics) to treat Hodgkin lymphoma (HL) and a rare lymphoma known as systemic anaplastic large cell lymphoma (ALCL). Adcetris is to be used in patients with HL whose disease has progressed after autologous stem cell transplant or after two prior chemotherapy treatments for those who cannot receive a transplant. Adcetris may also be used in patients with ALCL whose disease has progressed after one prior chemotherapy treatment.

The effectiveness of Adcetris in patients with HL was evaluated in a single clinical trial involving 102 patients. In the single-arm trial, patients were only treated with Adcetris. The study\'s primary endpoint was objective response rate, the percentage of patients who experienced complete or partial cancer shrinkage or disappearance after treatment. Seventy-three percent of patients achieved either a complete or partial response to the treatment. On average, these patients responded to the therapy for 6.7 months.

The effectiveness of Adcetris in patients with systemic ALCL was evaluated in a single clinical trial in 58 patients. In the single-arm trial, patients were only treated with Adcetris. The trial\'s primary endpoint was objective response rate. Of the patients receiving Adcetris for ALCL, 86% experienced either a complete or partial response and responded on average for 12.6 months.