Ploessl Cady, Pan Alice, Maples Kathryn T, Lowe Denise K
Virginia Commonwealth University Health System/Medical College of Virginia Hospitals, Richmond, VA, USA.
Virginia Commonwealth University Health System/Medical College of Virginia Hospitals, Richmond, VA, USA
Ann Pharmacother. 2016 May;50(5):416-22. doi: 10.1177/1060028016632013. Epub 2016 Feb 25.
To review the pharmacology, pharmacokinetics, efficacy, safety, dosage and administration, and formulary considerations for dinutuximab.
MEDLINE was searched (1964 to January 2016) using the terms ch14.18, dinutuximab, immunotherapy, and neuroblastoma. Other information was identified from package insert, Biologics License Application, abstracts, news releases, and ClinicalTrials.gov.
Identified English-language articles were reviewed. Selected studies included phase I through III.
High-risk neuroblastoma is primarily a childhood cancer with 5-year survival rates of 40% to 50%. Treatment for high-risk neuroblastoma includes induction chemotherapy, surgery, myeloablative chemotherapy with autologous hematopoietic stem cell transplant, and radiation therapy. For patients achieving clinical remission, limited treatments exist for preventing relapse. Dinutuximab is a chimeric, human-murine, anti-GD2 monoclonal antibody approved in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), aldesleukin (interleukin-2 [IL-2]), and isotretinoin (13-cis-retinoic acid [RA]) for maintenance treatment of pediatric patients with high-risk neuroblastoma who achieve at least a partial response to first-line multiagent, multimodality therapy. In phase III trials, dinutuximab increased 2-year event-free survival and overall survival when compared to standard treatment. Severe adverse effects of dinutuximab include pain, hypersensitivity reactions, capillary leak syndrome, and hypotension.
Dinutuximab is the first anti-GD2 monoclonal antibody approved in combination with GM-CSF, IL-2, and RA for maintenance treatment of pediatric patients with high-risk neuroblastoma who achieve at least a partial response to first-line multiagent, multimodality therapy. Ongoing research will determine if dinutuximab could be used earlier in treatment, in nonresponders to initial therapies, in combination with chemotherapy, or in other cancers.
综述地努图希单抗的药理学、药代动力学、疗效、安全性、用法用量及处方相关考量。
使用检索词ch14.18、地努图希单抗、免疫疗法和成神经细胞瘤检索MEDLINE（1964年至2016年1月）。其他信息来自药品说明书、生物制品许可申请、摘要、新闻稿及ClinicalTrials.gov。
对检索到的英文文章进行综述。入选研究包括I期至III期试验。
高危成神经细胞瘤主要是一种儿童癌症，5年生存率为40%至50%。高危成神经细胞瘤的治疗包括诱导化疗、手术、自体造血干细胞移植的清髓性化疗及放射治疗。对于达到临床缓解的患者，预防复发的治疗手段有限。地努图希单抗是一种嵌合的人鼠抗GD2单克隆抗体，被批准与粒细胞巨噬细胞集落刺激因子（GM-CSF）、阿地白介素（白介素-2 [IL-2]）和异维A酸（13-顺式维甲酸[RA]）联合用于一线多药、多模式治疗至少获得部分缓解的高危成神经细胞瘤儿科患者的维持治疗。在III期试验中，与标准治疗相比，地努图希单抗提高了2年无事件生存率和总生存率。地努图希单抗的严重不良反应包括疼痛、过敏反应、毛细血管渗漏综合征和低血压。
地努图希单抗是首个被批准与GM-CSF、IL-2和RA联合用于一线多药、多模式治疗至少获得部分缓解的高危成神经细胞瘤儿科患者维持治疗的抗GD2单克隆抗体。正在进行的研究将确定地努图希单抗是否可在治疗早期、初始治疗无反应者、与化疗联合或用于其他癌症中使用。
