当前位置:科学网首页 > 小柯机器人 >详情
塞鲁米替尼治疗无法手术的丛状神经纤维瘤患儿疗效显著
作者:小柯机器人 发布时间:2020/3/29 22:57:09

美国国立卫生研究院Andrea M. Gross课题组在研究中取得进展。他们研究了塞鲁米替尼治疗无法手术的丛状神经纤维瘤患儿的疗效。相关论文于2020年3月18日发表于《新英格兰医学杂志》上。

对于1型神经纤维瘤患者,尚无针对无法手术的丛状神经纤维瘤的标准疗法。

研究组进行了一项开放标签的临床2期试验,以确定塞鲁米替尼对丛状神经纤维瘤患者的客观缓解率并评估临床获益。

2015年8月至2016年8月,研究组招募了50名患有1型神经纤维瘤和有症状的无法手术的丛状神经纤维瘤的儿童,中位年龄为10.2岁,每日口服塞鲁米替尼进行治疗,28天为一个周期,每周期对孩子们进行临床评估。肿瘤疼痛强度的评分范围为0-10分,分数越高越痛。

与神经纤维瘤相关的最常见症状是毁容(44名)、运动功能障碍(33名)和疼痛(26名)。截至2019年3月29日,共有35例患者(70%)部分缓解,其中28例长期缓解(持续≥1年)。治疗1年后,患儿的肿瘤疼痛强度评分平均下降2分,临床改善明显。

此外,由患儿或父母报告的疼痛干扰、整体健康相关的生活质量、力量和运动范围的功能性结局等方面均有临床意义上的改善。5名患儿疑因塞鲁米替尼的毒副作用而中止治疗,还有6名患儿病情进展。最常见的毒副作用是恶心、呕吐或腹泻;肌酸磷酸激酶水平无症状增加;痤疮样皮疹;甲沟炎。

总之,塞鲁米替尼治疗1型神经纤维瘤和无法手术的丛状神经纤维瘤儿童具有持久的肿瘤缩小作用,患儿可从中获益。

附:英文原文

Title: Selumetinib in Children with Inoperable Plexiform Neurofibromas

Author: 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.

Issue&Volume: 2020-03-18

Abstract: AbstractBackgroundNo approved therapies exist for inoperable plexiform neurofibromas in patients with neurofibromatosis type 1.MethodsWe conducted an open-label, phase 2 trial of selumetinib to determine the objective response rate among patients with plexiform neurofibromas and to assess clinical benefit. Children with neurofibromatosis type 1 and symptomatic inoperable plexiform neurofibromas received oral selumetinib twice daily at a dose of 25 mg per square meter of body-surface area on a continuous dosing schedule (28-day cycles). Volumetric magnetic resonance imaging and clinical outcome assessments (pain, quality of life, disfigurement, and function) were performed at least every four cycles. Children rated tumor pain intensity on a scale from 0 (no pain) to 10 (worst pain imaginable).ResultsA total of 50 children (median age, 10.2 years; range, 3.5 to 17.4) were enrolled from August 2015 through August 2016. The most frequent neurofibroma-related symptoms were disfigurement (44 patients), motor dysfunction (33), and pain (26). A total of 35 patients (70%) had a confirmed partial response as of March 29, 2019, and 28 of these patients had a durable response (lasting ≥1 year). After 1 year of treatment, the mean decrease in child-reported tumor pain-intensity scores was 2 points, considered a clinically meaningful improvement. In addition, clinically meaningful improvements were seen in child-reported and parent-reported interference of pain in daily functioning (38% and 50%, respectively) and overall health-related quality of life (48% and 58%, respectively) as well as in functional outcomes of strength (56% of patients) and range of motion (38% of patients). Five patients discontinued treatment because of toxic effects possibly related to selumetinib, and 6 patients had disease progression. The most frequent toxic effects were nausea, vomiting, or diarrhea; an asymptomatic increase in the creatine phosphokinase level; acneiform rash; and paronychia.ConclusionsIn this phase 2 trial, most children with neurofibromatosis type 1 and inoperable plexiform neurofibromas had durable tumor shrinkage and clinical benefit from selumetinib.

DOI: 10.1056/NEJMoa1912735

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa1912735

 

期刊信息

The New England Journal of Medicine:《新英格兰医学杂志》,创刊于1812年。隶属于美国麻省医学协会,最新IF:70.67
官方网址:http://www.nejm.org/
投稿链接:http://www.nejm.org/page/author-center/home