Division of Oncology, Center for Cancer and Blood Disorders, Children's National Medical Center, Washington, District of Columbia, USA.
Pediatr Blood Cancer. 2013 May;60(5):776-82. doi: 10.1002/pbc.24297. Epub 2012 Sep 13.
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.
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.
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, 1-12 years). Median treatment duration was 12 months (range, 1-24 months). 12 patients had an objective response; 2 had stable disease. Median time to maximum response was 9 weeks (range, 7-17 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.
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.
由于对小儿低级别胶质瘤（LGG）进行确定性切除或放疗可能会带来严重且永久性的不良反应，因此医学治疗已发挥重要作用。贝伐珠单抗为基础的治疗已显示出令人鼓舞的疗效；然而，其长期毒性、反应持久性和替代给药方案尚未得到评估。
这是一项回顾性研究，纳入了接受贝伐珠单抗为基础的治疗且治疗完成后至少随访 12 个月的、患有多发复发性进行性 LGG 的儿童。所有毒性均进行统一分级，影像学检查由中心进行评估。
所有 14 名患者均至少经历过两种先前治疗方案的失败，其中 6 名患者有播散。患者接受初始贝伐珠单抗治疗的中位年龄为 5.3 岁（范围，1-12 岁）。中位治疗持续时间为 12 个月（范围，1-24 个月）。12 名患者有客观缓解，2 名患者疾病稳定。最大缓解时间的中位数为 9 周（范围，7-17 周）。尽管 13/14 名患者在停止贝伐珠单抗治疗后中位时间为 5 个月时进展，但没有患者在治疗期间进展。4 名患者重新接受了贝伐珠单抗治疗，所有患者再次缓解或稳定。替代给药方案也是有效的，包括贝伐珠单抗单药治疗和延长给药间隔至 3 周。3 级贝伐珠单抗相关毒性包括蛋白尿（n=2）、原发性炎症性关节炎（n=1）和嗜睡（n=1）。除 1 例高血压外，所有毒性在治疗停止后 6 个月内均得到缓解。
贝伐珠单抗为基础的治疗可迅速诱导 LGG 缓解。停止治疗后进展的患者可以成功地重新接受贝伐珠单抗治疗。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。
