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.