Emma Children's Hospital, Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Pediatric Oncology, Amsterdam, The Netherlands.
Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
J Neurooncol. 2021 Jun;153(2):263-271. doi: 10.1007/s11060-021-03763-1. Epub 2021 May 7.
This study investigates the safety, tolerability, and preliminary efficacy of combined treatment with VEGF inhibitor bevacizumab, topoisomerase I inhibitor irinotecan, and EGFR inhibitor erlotinib in children with progressive diffuse intrinsic pontine glioma (DIPG).
Biweekly bevacizumab (10 mg/kg) and irinotecan (125 mg/m) were combined with daily erlotinib. Two cohorts received increasing doses of erlotinib (65 and 85 mg/m) following a 3 + 3 dose-escalation schedule, until disease progression with a maximum of one year. Dose-limiting toxicities (DLT) were monitored biweekly. Secondary progression free survival (sPFS) and overall survival (OS) were determined based on clinical and radiological response measurements. Quality of life (QoL) during treatment was also assessed.
Between November 2011 and March 2018, nine patients with disease progression after initial radiotherapy were enrolled. Median PFS at start of the study was 7.3 months (range 3.5-10.0). In the first dose cohort, one patient experienced a DLT (grade III acute diarrhea), resulting in enrollment of three additional patients in this cohort. No additional DLTs were observed in consecutive patients receiving up to a maximum dose of 85 mg/m. Median sPFS was 3.2 months (range 1.0-10.9), and median OS was 13.8 months (range 9.3-33.0). Overall QoL was stable during treatment.
Daily erlotinib is safe and well tolerated in doses up to 85 mg/m when combined with biweekly bevacizumab and irinotecan in children with progressive DIPG. Median OS of the study patients was longer than known form literature.
本研究旨在探讨血管内皮生长因子抑制剂贝伐珠单抗、拓扑异构酶 I 抑制剂伊立替康和表皮生长因子受体抑制剂厄洛替尼联合治疗进展性弥漫性内在脑桥胶质瘤（DIPG）患儿的安全性、耐受性和初步疗效。
每周两次给予贝伐珠单抗（10mg/kg）和伊立替康（125mg/m²），并联合每日厄洛替尼。根据 3+3 剂量递增方案，在疾病进展前，两组患者接受递增剂量的厄洛替尼（65 和 85mg/m²），最多治疗 1 年。每周监测剂量限制毒性（DLT）。根据临床和影像学反应测量，确定次要无进展生存期（sPFS）和总生存期（OS）。治疗期间的生活质量（QoL）也进行了评估。
2011 年 11 月至 2018 年 3 月，9 名在初始放疗后疾病进展的患者入组。研究开始时的中位 PFS 为 7.3 个月（范围 3.5-10.0）。在第一剂量组中，1 名患者出现 DLT（III 级急性腹泻），导致该组再入组 3 名患者。连续接受最高 85mg/m²剂量的患者未观察到其他 DLT。中位 sPFS 为 3.2 个月（范围 1.0-10.9），中位 OS 为 13.8 个月（范围 9.3-33.0）。治疗期间整体 QoL 稳定。
在进展性 DIPG 患儿中，每周两次贝伐珠单抗和伊立替康联合每日厄洛替尼，厄洛替尼剂量高达 85mg/m²时是安全且耐受良好的。本研究患者的中位 OS 长于文献报道。
