Conflict of interest: Dr. Packer has consulted for PTC Pharmaceuticals, Dr. Jakacki has consulted for OSI Pharmaceuticals.
Long-term efficacy and toxicity of bevacizumab-based therapy in children with recurrent low-grade gliomas†
Article first published online: 13 SEP 2012
Copyright © 2012 Wiley Periodicals, Inc.
Pediatric Blood & Cancer
Volume 60, Issue 5, pages 776–782, May 2013
How to Cite
Hwang, E. I., Jakacki, R. I., Fisher, M. J., Kilburn, L. B., Horn, M., Vezina, G., Rood, B. R. and Packer, R. J. (2013), Long-term efficacy and toxicity of bevacizumab-based therapy in children with recurrent low-grade gliomas. Pediatr. Blood Cancer, 60: 776–782. doi: 10.1002/pbc.24297
- Issue published online: 14 MAR 2013
- Article first published online: 13 SEP 2012
- Manuscript Accepted: 2 AUG 2012
- Manuscript Received: 11 JUL 2012
- Gilbert Neurofibromatosis Institute
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. Pediatr Blood Cancer 2013; 60: 776–782. © 2012 Wiley Periodicals, Inc.