Department of Pediatric and Adolescent Oncology, Institut Gustave Roussy, University Paris-Saclay, Villejuif, France.
Pediatric Intensive Care Unit, Necker-Enfants Malades University Hospital Assistance Publique-Hôpitaux de Paris, Université de Paris, Paris, France.
J Neurooncol. 2022 Apr;157(2):355-364. doi: 10.1007/s11060-022-03970-4. Epub 2022 Mar 3.
At least half of children with low-grade glioma (LGG) treated with first line chemotherapy experience a relapse/progression and may therefore need a second-line chemotherapy. Irinotecan-bevacizumab has been recommended in this setting in France after encouraging results of pilot studies. We performed a retrospective analysis to define the efficacy, toxicity and predictors for response to the combination on a larger cohort.
We reviewed the files from children < 19 years of age with progressive or refractory LGG treated between 2009 and 2016 in 7 French centers with this combination.
72 patients (median age 7.8 years [range 1-19]) received a median of 16 courses (range 3-30). The median duration of treatment was 9 months (range 1.4-16.2). 96% of patients experienced at least disease stabilization. The 6-month and 2-year progression-free survivals (PFS) were 91.7% [IC 95% 85.5-98.3] and 38.2% [IC 95% 28.2-51.8] respectively. No progression occurred after treatment in 18 patients with a median follow-up of 35.6 months (range 7.6-75.9 months). Younger patients had a worse PFS (p = 0.005). Prior chemoresistance, NF1 status, duration of treatment, histopathology or radiologic response did not predict response. The most frequent toxicities related to bevacizumab included grades 1-2 proteinuria in 21, epistaxis in 10, fatigue in 12 and hypertension in 8 while gastro-intestinal toxicity was the most frequent side effect related to irinotecan.
Bevacizumab-irinotecan has the potential of disease control clinically and radiographically in children with recurrent LGG whatever their previous characteristics; in many cases however these responses are not sustained, especially in younger children.
至少一半接受一线化疗治疗的低级别胶质瘤（LGG）患儿会出现复发/进展，因此可能需要二线化疗。在法国，在一些试点研究取得令人鼓舞的结果后，伊立替康联合贝伐珠单抗已被推荐用于该治疗环境。我们对 7 个法国中心的更大队列进行了回顾性分析，以确定该联合用药的疗效、毒性和反应预测因素。
我们回顾了 2009 年至 2016 年间，7 个法国中心治疗进展或难治性 LGG 的 72 名年龄<19 岁的儿童患者的病历。
72 名患者（中位年龄 7.8 岁[范围 1-19]）接受了中位数为 16 个疗程（范围 3-30）的治疗。中位治疗时间为 9 个月（范围 1.4-16.2）。96%的患者至少经历了疾病稳定。6 个月和 2 年无进展生存率（PFS）分别为 91.7%（95%CI 85.5-98.3）和 38.2%（95%CI 28.2-51.8）。18 名患者在中位随访 35.6 个月（范围 7.6-75.9 个月）后无进展。年龄较小的患者 PFS 较差（p=0.005）。化疗耐药、NF1 状态、治疗持续时间、组织病理学或影像学反应均不能预测疗效。与贝伐珠单抗相关的最常见毒性反应包括 21 例 1-2 级蛋白尿、10 例鼻出血、12 例疲劳和 8 例高血压，而伊立替康最常见的胃肠道毒性。
贝伐珠单抗联合伊立替康具有控制复发性 LGG 患儿疾病的潜力，无论其既往特征如何；然而，在许多情况下，这些反应并不能持续，尤其是在年龄较小的儿童中。
