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司美替尼治疗不能手术的丛状神经纤维瘤患儿
Selumetinib in Children with Inoperable Plexiform Neurofibromas


Andrea M. Gross ... 肿瘤 妇产科和儿科 • 2020.04.09

摘要


背景

对于1型神经纤维瘤病患儿的不能手术的丛状神经纤维瘤,目前尚无获得批准的疗法。

 

方法

我们对司美替尼(selumetinib)开展了一项开放标签的2期试验,旨在确定丛状神经纤维瘤患儿的客观缓解率并评估临床益处。患不能手术的有症状丛状神经纤维瘤的1型神经纤维瘤病患儿接受了司美替尼连续口服给药(给药周期为28日),剂量为每日2次,每次25 mg/m2体表面积。我们至少每4个周期对患儿进行1次体积磁共振成像和临床结局评估(疼痛、生活质量、毁容和功能)。儿童使用评分范围为0(无疼痛)~10分(可以想象的最严重疼痛)的量表评估肿瘤疼痛的严重程度。

 

结果

从2015年8月至2016年8月,本研究共纳入了50名患儿(中位年龄,10.2岁;范围,3.5~17.4)。最常见的神经纤维瘤相关症状包括毁容(44名患儿)、运动功能障碍(33)和疼痛(26)。截至2019年3月29日,共计35名患儿(70%)达到了经证实的部分缓解,其中28名达到了持久缓解(持续≥1年)。治疗1年之后,儿童报告的肿瘤疼痛严重程度评分平均降低了2分,我们认为这个属于有临床意义的改善。此外,在儿童报告和父母报告的疼痛对日常功能(分别为38%和50%)和总体健康相关生活质量(分别为48%和58%)的干扰,以及在关于力量(56%的患儿)和关节活动范围(38%的患儿)的功能结局方面,我们均观察到了有临床意义的改善。5名患儿因为与司美替尼可能相关的毒性作用停止治疗,6名患儿发生了疾病进展。最常见的毒性作用为恶心、呕吐或腹泻、无症状的肌酸磷酸激酶水平升高、痤疮样皮疹及甲沟炎。

 

结论

在这项2期试验中,在患不能手术的丛状神经纤维瘤的大多数1型神经纤维瘤病患儿中,司美替尼产生了持久的缩小肿瘤作用和临床益处(由美国国立卫生研究院院内研究计划[Intramural Research Program]等资助,在ClinicalTrials.gov注册号为NCT01362803)。





作者信息

Andrea M. Gross, M.D., Pamela L. Wolters, Ph.D., Eva Dombi, M.D., Andrea Baldwin, P.N.P., Patricia Whitcomb, R.N., Michael J. Fisher, M.D., Brian Weiss, M.D., AeRang Kim, M.D., Ph.D., Miriam Bornhorst, M.D., Amish C. Shah, M.D., Ph.D., Staci Martin, Ph.D., Marie C. Roderick, Psy.D., Dominique C. Pichard, M.D., Amanda Carbonell, R.N., Scott M. Paul, M.D., R.M.D., Janet Therrien, B.S., Oxana Kapustina, M.L., Kara Heisey, B.S., D. Wade Clapp, M.D., Ph.D., Chi Zhang, Ph.D., Cody J. Peer, Ph.D., William D. Figg, Pharm.D., Malcolm Smith, M.D., Ph.D., John Glod, M.D., Ph.D., Jaishri O. Blakeley, M.D., Seth M. Steinberg, Ph.D., David J. Venzon, Ph.D., L. Austin Doyle, M.D., and Brigitte C. Widemann, M.D.
From the Pediatric Oncology Branch (A.M.G., P.L.W., E.D., P.W., S.M., M.C.R., D.C.P., A.C., J.T., O.K., J.G., B.C.W.) and the Clinical Pharmacology Program (C.J.P., W.D.F.), Center for Cancer Research, National Cancer Institute, and the Rehabilitation Medicine Department, Clinical Center (S.M.P), National Institutes of Health, Bethesda, the Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick (A.B., K.H.), the Cancer Therapy Evaluation Program (M.S., L.A.D.) and the Biostatistics and Data Management Section, Center for Cancer Research (S.M.S., D.J.V.), National Cancer Institute, National Institutes of Health, Shady Grove, and Johns Hopkins University School of Medicine, Baltimore (J.O.B.) — all in Maryland; Children’s Hospital of Philadelphia, Philadelphia (M.J.F., A.C.S.); Cincinnati Children’s Hospital, Cincinnati (B.W.); Children’s National Hospital, Washington, DC (A.K., M.B.); and Indiana University School of Medicine, Indianapolis (D.W.C., C.Z.). Address reprint requests to Dr. Gross at the Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Bldg. 10, Rm. 1-5742, Bethesda, MD 20892, or at andrea.gross@nih.gov.

 

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