Long-term efficacy and toxicity of bevacizumab-based therapy in children with recurrent low-grade gliomas
Long-term efficacy and toxicity of bevacizumab-based therapy in children with recurrent low-grade gliomas
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DOI：
10.1002/pbc.24297
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发表时间：
2013-05-01
影响因子：
3.2
通讯作者：
Packer, Roger J.
中科院分区：
文献类型：
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作者：
Hwang, Eugene I.;Jakacki, Regina I.;Packer, Roger J.
背景 由于儿科低级别胶质瘤（LGG）的根治性切除或放疗可能与严重且永久性的不良反应相关，因此医疗管理发挥了重要作用。基于贝伐珠单抗的治疗已显示出令人鼓舞的反应；然而，尚未评估长期毒性、反应持久性和替代给药方案。程序 这是对接受基于贝伐单抗治疗的多发性复发、进行性 LGG 儿童的回顾性评价，并在治疗完成后随访至少 12 个月。毒性被统一分级，影像学被集中审查。结果所有 14 名患者之前至少有两种治疗方案均失败；六是有传播。患者接受初始贝伐单抗治疗的中位年龄为 5.3 岁（范围为 112 岁）。中位治疗持续时间为 12 个月（范围 124 个月）。 12名患者有客观缓解； 2 例病情稳定。达到最大反应的中位时间为 9 周（范围为 717 周）。尽管 13/14 的患者在停止贝伐单抗后中位 5 个月后病情出现进展，但没有患者在治疗中出现进展。四名患者接受贝伐珠单抗再次治疗，全部再次缓解或稳定。替代给药策略是有效的，包括贝伐珠单抗单药治疗和将给药间隔延长至 3 周。贝伐珠单抗相关的高级别毒性包括 3 级蛋白尿 (n=2)、原发性炎症性关节炎 (n=1) 和嗜睡 (n=1)。除一例高血压外，毒性反应在停止治疗后 6 个月内得到缓解。结论 基于贝伐珠单抗的治疗成功地诱导了快速 LGG 反应。治疗结束后病情进展的患者可以成功地用贝伐珠单抗进行再治疗。一旦停止治疗，几乎所有肿瘤都会进展。毒性并非微不足道，但通常是可逆的。儿科血癌2013； 60: 776782。(c) 2012 年 Wiley 期刊公司。
Background Because definitive resection or radiotherapy for pediatric low-grade gliomas (LGGs) may be associated with severe and permanent adverse effects, medical management has taken a significant role. Bevacizumab-based therapy has demonstrated encouraging responses; however, longer-term toxicity, response durability and alternative dosing regimens have not been evaluated. Procedure This was a retrospective review of children with multiply recurrent, progressive LGGs treated with bevacizumab-based therapy and followed for at least 12 months after treatment completion. Toxicity was uniformly graded and imaging was centrally reviewed. Results All fourteen patients had failed at least two prior treatment regimens; six had dissemination. Patients received initial bevacizumab-based therapy at a median age of 5.3 years (range, 112 years). Median treatment duration was 12 months (range, 124 months). 12 patients had an objective response; 2 had stable disease. Median time to maximum response was 9 weeks (range, 717 weeks). No patients progressed on therapy, although 13/14 progressed after stopping bevacizumab at a median of 5 months. Four patients were re-treated with bevacizumab and all again responded or stabilized. Alternative dosing strategies were effective, including bevacizumab monotherapy and prolonging the dosing interval to 3 weeks. High-grade bevacizumab-related toxicities consisted of grade 3 proteinuria (n=2), primary inflammatory arthritis (n=1), and somnolence (n=1). Toxicities resolved within 6 months of treatment cessation except one case of hypertension. Conclusions Bevacizumab-based therapy is successful at inducing rapid LGG response. Patients progressing off-therapy may be successfully re-treated with bevacizumab. Nearly all tumors progress once treatment is discontinued. Toxicities are not insignificant but usually reversible. Pediatr Blood Cancer 2013; 60: 776782. (c) 2012 Wiley Periodicals, Inc.