Use of bevacizumab as a single agent or in adjunct with traditional chemotherapy regimens in children with unresectable or progressive low‐grade glioma

Abstract

In pediatric low‐grade gliomas not amenable to complete resection, various chemotherapy regimens are the mainstream of treatment. An excellent overall survival of these patients makes justification of the intensification of chemotherapy difficult and calls for the development of new strategies. Bevacizumab, a humanized monoclonal antibody directed against Vascular endothelial growth factor (VEGF), has been successfully used in combination with irinotecan in a number of adult and pediatric studies and reports. Fifteen patients at median age of 7 years old (range 3 months to 15 years) were treated with bevacizumab in combination with conventional low‐toxicity chemotherapy. The majority had chiasmatic/hypothalamic and midline tumors, seven had confirmed BRAF pathway alterations including neurofibromatosis type 1 (2). Fourteen patients had more than one progression and three had radiotherapy. No deaths were documented, PFS at 11 and 15 months was 71.5% ± 13.9% and 44.7% ± 17.6% respectively. At the end of follow‐up 40% of patients has radiologically stable disease, three patients progressed shortly after completion of bevacizumab and two showed mixed response with progression of cystic component. Rapid visual improvement was seen in 6/8 patients, resolution of endocrine symptoms in 2/4 and motor function improvement in 4/6. No relation between histology or BRAF status and treatment response was observed. Treatment‐limiting toxicities included grade 4 proteinuria (2) and hypertension (2) managed with cessation (1) and pausing of therapy plus antihypertensives (1). In conclusion, bevacizumab is well tolerated and appears most effective for rapid tumor control to preserve vision and improve morbidity.

Targeting IL-6 Is a Potential Treatment for Primary Cystic Craniopharyngioma

“…No research has been done on the use of bevacizumab in ACP patients, but one small case series reviewed the use of bevacizumab in three patients with pilocytic astrocytoma (PA), another predominantly cystic tumor, and found that all three patients tolerated the therapy well and resulted in a decrease cyst volumes (22). Bevacizumab has also been shown recently to have clinical and radiographic effects in adult PA patients (23, 24) and has been shown to be a safe and tolerated therapy in pediatric patients with PA and other forms of low-grade glioma (25, 26). Overall, the patients presented tolerated therapy well without significant side effects or complications other than isolated Grade 3 neutropenia without associated infections.…”

Use of Antiangiogenic Therapies in Pediatric Solid Tumors

“…In fact, bevacizumab as a single agent reduces tumor volume and apparent diffusion coefficient [ 16 , 56 , 57 ], and improves field of vision, cranial neuropathy, strength, and gait without tumor progression in some cases [ 58 ]. The combination of bevacizumab with conventional chemotherapy is well tolerated and more effective in preserving vision and improving mobility in patients with inoperable or progressive low-grade glioma [ 59 ]. It also helps to preserve vision in patients with optic pathway gliomas in combination with carboplatin or proton-beam radiation [ 60 ].…”

A systematic review of ongoing clinical trials in optic pathway gliomas

“…Bevacizumab A humanised monoclonal antibody directed against VEGF, this inhibition leads to a reduction in microvascular growth of tumour blood vessels and thus limits the blood supply to tumour tissues. There are several reports of the benefit of anti-VEGF drugs in uncontrolled case series [35][36][37][38].…”