Unituxin (dinutuximab Injection ) 获美国FDA批准对高风险神经母细胞瘤第一个治疗
美国FDA药品评价和研究中心血液学和肿瘤产品室主任Richard Pazdur，M.D.说：“Unituxin 标记第一个批准为一种治疗目标特异性地针对有高风险神经母细胞瘤患者的治疗，”“Unituxin满足提供一种治疗选择延长有高风险神经母细胞瘤儿童活存至关重要的选择。”
优先审评和孤儿产品指定。FDA还发出一个罕见儿科疾病优先审评证件至United Therapeutics公司
批准日期： 2015年3月10日；公司：United Therapeutics Corporation
UNITUXIN(dinutuximab)injection-为静脉使用
美国初次批准：2015
适应证和用途
Unituxin是一种GD2-结合单克隆抗体适用与粒细胞 - 巨噬细胞集落刺激因子(GM-CSF)，白介素-2(IL-2)，和13-顺 - 视黄酸(RA)联用，为一线多药，多模式治疗前实现至少部分缓解反应有高风险神经母细胞瘤儿童患者的治疗。
剂量和给药方法
17.5mg/m2/day作为一个历时10 to 20小时稀释的静脉输注连续4天共至5个疗程。
剂型和规格
注射液：17.5mg/5mL(3.5mg/mL)在一个单次使用小瓶。
禁忌证
对dinutuximab过敏反应史。
警告和注意事项
⑴毛细血管渗漏综合征和低血压：治疗期间需要给予预水化和严密监视患者。依赖于严重程度，通过中断，输注速率减慢处理，或永久终止。
⑵感染：中断直至全身感染的解决。
⑶眼神经学疾病：对散大瞳孔对光反射迟钝或其他视觉障碍中断和对复发性眼部疾病或失明永久终止。
⑷骨髓抑制：Unituxin治疗期间监视外周血细胞计数。
⑸电解质异常：密切监视血清电解质。
⑹不典型溶血性尿毒症综合征：永久终止Unituxin和开始支持处理。
⑺胚胎胎儿毒性：可能致胎儿危害。忠告有生殖潜能女性对胎儿潜在风险和使用有效避孕。
不良反应
最常见不良药物反应(≥ 25%)是疼痛，发热，血小板减少，淋巴细胞减少，输注反应，低血压，低钠血症，谷丙转氨酶增加，贫血，呕吐，腹泻，低钾血症，毛细血管渗漏综合征，中性粒细胞减少，荨麻疹，低白蛋白血症，谷草转氨酶增加，和低钙血症。最常见严重不良反应(≥ 5%)是感染，输注反应，低钾血症，低血压，疼痛，发热，和毛细血管渗漏综合征。

 

Unituxin (dinutuximab) is a chimeric monoclonal antibody.
Unituxin is specifically indicated for use in combination with granulocyte-macrophage colonystimulating factor (GM-CSF), interleukin-2 (IL-2) and 13-cis-retinoic acid (RA), for the treatment of pediatric patients with high-risk neuroblastoma who achieve at least a partial response to prior first-line multiagent, multimodality therapy.
Unituxin is supplied as a solution for intravenous infusion. The recommended dose of Unituxin is 17.5mg/m2/day administered as an intravenous infusion over 10 to 20 hours for 4 consecutive days for a maximum of 5 cycles. Unituxin should be initiated at an infusion rate of 0.875 mg/m2 /hour for 30minutes. The infusion rate can be gradually increased as tolerated to a maximum rate of 1.75mg/m2/hour. Follow dose modification instructions (see drug label) for adverse reactions.
UNITUXIN Rx
Pharmacological Class:
GD2-binding monoclonal antibody.

Active Ingredient(s):
Dinutuximab 3.5mg/mL; solution for IV infusion after dilution; preservative-free.

Company
United Therapeutics Corp
Indication(s):
In combination with granulocyte-macrophage colony-stimulating factor, interleukin-2 (IL-2) and 13-cis-retinoic acid (RA), for the treatment of children with high-risk neuroblastoma who achieve at least a partial response to prior first-line multiagent, multimodality therapy.

Pharmacology:
Dinutuximab binds to cell surface GD2 and induces cell lysis of GD2-expressing cells through antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity.

Clinical Trials:
The safety and efficacy of Unituxin was eva luated in a randomized, open-label, multicenter trial conducted in pediatric patients with high-risk neuroblastoma.

Patients were randomized between Day 50 and Day 77 post-autologous stem cell transplantation. Patients randomized to the Unituxin/RA arm (n=113) received up to five cycles of dinutuximab in combination with GM-CSF or IL-2 plus RA, followed by one cycle of RA alone. Patients randomized to the RA arm (n=113) received six cycles of RA. Dinutuximab was administered at a dose of 17.5mg/m2/day on four consecutive days. Patients in both treatment arms received six cycles of RA at a dose of 160mg/m2/day orally (for patients weighing >12kg) or 5.33mg/kg/day (for patients weighing ≤12kg) in two divided doses for 14 consecutive days.

The major efficacy outcome measure was investigator-assessed event-free survival (EFS), defined as the time from randomization to the first occurrence of relapse, progressive disease, secondary malignancy, or death. There were 33 (29%) events in the Unituxin/RA arm vs. 50 (44%) in the RA arm (HR 0.57; [95% CI: 0.37, 0.89]; P= 0.01). Overall survival (OS) was also eva luated. After observing improvement in EFS based on the seventh interim analysis, termination of accrual was recommended.

For more clinical trial data, see full labeling.

Legal Classification:
Rx

Adults:
Not applicable.

Children:
Confirm adequate hematologic, respiratory, hepatic, and renal function prior to each course. Hydrate and premedicate with antihistamines, analgesics (eg, IV opioids), and antipyretics prior to each dose: see full labeling. Give via IV infusion over 10–20 hours for 4 consecutive days; max 5 cycles. Initial rate: 0.875mg/m2/hr for 30mins; may gradually increase as tolerated up to max 1.75mg/m2/hr. Cycles 1, 3, and 5 (24-day cycle): 17.5mg/m2/day on Days 4–7. Cycles 2 and 4 (32-day cycle): 17.5mg/m2/day on Days 8–11. Dose modifications: see full labeling.

Warnings/Precautions:
Risk of serious infusion reactions; monitor during and at least 4 hours after completion of each infusion; interrupt or discontinue if severe or prolonged infusion reactions occur. Have resuscitative medications and equipment available. Risk of neuropathy. Permanently discontinue if life-threatening infusion reactions, Grade 3 pain unresponsive to max supportive measures, Grade 4 sensory neuropathy or Grade 3 sensory neuropathy that interferes with daily activities for more than 2 weeks, Grade 2 peripheral motor neuropathy, recurrent signs of eye disorders or vision loss, signs of atypical hemolytic uremic syndrome occurs. Interrupt or discontinue if severe capillary leak syndrome, symptomatic hypotension, systolic BP less than lower limit of normal for age or decreased by >15% compared to baseline develops. Monitor for systemic infection; temporarily discontinue until resolves. Monitor BP, peripheral blood counts during therapy, and serum electrolytes daily. Renal or hepatic impairment. Pregnancy; avoid. Use effective contraception during therapy and for at least 2 months after last dose. Nursing mothers: not recommended.

Adverse Reaction(s)
Pain, pyrexia, infusion reactions, hypotension, hyponatremia, hypokalemia, hypocalcemia, hypoalbuminemia, increased ALT/AST, vomiting, diarrhea, capillary leak syndrome, urticaria, infections, bone marrow suppression (eg, thrombocytopenia, anemia, neutropenia, lymphopenia).

How Supplied:
Single-use vial (5mL)—1