Clinical and Translational Oncology

, Volume 18, Issue 5, pp 464–468 | Cite as

Safety of bevacizumab in patients younger than 4 years of age

  • N. C. Millan
  • M. J. Poveda
  • O. Cruz
  • J. MoraEmail author
Research Article



Limited data exist regarding the safety and efficacy of bevacizumab in pediatric patients under the age of 4 years. Here, we report a large cohort of pediatric patients under 4 years of age treated with bevacizumab.


The primary objective was to document adverse events with a possible relationship to bevacizumab. Patients (n = 16) were identified through retrospective chart review and harbored a variety of conditions (44 % central nervous system (CNS) tumors, 31 % vascular anomalies, 13 % neuroblastoma, 12 % other).


The median age was 34.3 months (range 4.9–47.3), including five patients <2 years of age. Patients received bevacizumab for a median duration of 6.2 months, alone or with chemotherapy, and a median dose of 9.25 mg/kg (range 7.0–11.8). Partial responses were seen in 19 % of patients, and clinical improvements were seen in 69 %. Adverse events known to be associated with bevacizumab occurred in 37 %. Outcomes observed in this population resemble those reported for bevacizumab in older pediatric patients. The overall pattern and frequency of adverse events observed was similar to those seen in reports of older pediatric patients with a variety of conditions. The highest level of efficacy observed was seen among patients with vascular malformations or with low-grade CNS tumors.


Our results suggest that the use of bevacizumab is safe for the youngest children.


Bevacizumab Infant and toddlers Antiangiogenesis Infant tumors 



Support for third-party medical writing assistance was funded by Genentech, Inc.

Compliance with ethical standards

Conflict of interest

All authors declare no conflicts of interest to disclose.

Financial disclosure

The authors have no financial relationships relevant to this article to disclose.


  1. 1.
    Glade Bender J, Yamashiro DJ, Fox E. Clinical development of VEGF signaling pathway inhibitors in childhood solid tumors. Oncologist. 2011;16:1614–25.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Greenberger S, Bischoff J. Infantile hemangioma—mechanism(s) of drug action on a vascular tumor. Cold Spring Harb Perspect Med. 2011;1:a006460.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Megison ML, Gillroy LA, Beierle EA. Cell survival signaling in neuroblastoma. Anticancer Agents Med Chem. 2013;13:563–75.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Schiavetti A, Ingrosso A, Antenucci A, Federici T, Megaro G, De Luca L, et al. Circulating vascular endothelial growth factor in childhood solid tumors: plasma and serum measurements. Anticancer Res. 2012;32:3565–9.PubMedGoogle Scholar
  5. 5.
    Hintsala E, Bono P, Andersson S, Kivivuori SM. Quantification of plasma and bone marrow VEGF and angiopoietin-2 levels in pediatric malignancies. J Pediatr Hematol Oncol. 2012;34:503–10.CrossRefPubMedGoogle Scholar
  6. 6.
    Berendsen AD, Olsen BR. How vascular endothelial growth factor-A (VEGF) regulates differentiation of mesenchymal stem cells. J Histochem Cytochem. 2014;62:103–8.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Gerber HP, Hillan KJ, Ryan AM, Kowalski J, Keller GA, Rangell L, et al. VEGF is required for growth and survival in neonatal mice. Development. 1999;126:1149–59.PubMedGoogle Scholar
  8. 8.
    Aguilera D, Mazewski C, Fangusaro J, MacDonald TJ, McNall-Knapp RY, Hayes LL, et al. Response to bevacizumab, irinotecan, and temozolomide in children with relapsed medulloblastoma: a multi-institutional experience. Childs Nerv Syst. 2013;29:589–96.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    de Pasquale MD, Castellano A, de Sio L, de Laurentis C, Mastronuzzi A, Serra A, et al. Bevacizumab in pediatric patients: how safe is it? Anticancer Res. 2011;31:3953–7.PubMedGoogle Scholar
  10. 10.
    Narayana A, Gruber D, Kunnakkat S, Golfinos JG, Parker E, Raza S, et al. A clinical trial of bevacizumab, temozolomide, and radiation for newly diagnosed glioblastoma. J Neurosurg. 2012;116(2):341–5.CrossRefPubMedGoogle Scholar
  11. 11.
    Navid F, Baker SD, McCarville MB, Stewart CF, Billups CA, Wu J, et al. Phase I and clinical pharmacology study of bevacizumab, sorafenib, and low-dose cyclophosphamide in children and young adults with refractory/recurrent solid tumors. Clin Cancer Res 2013;19:236–246. Erratum in: Clin Cancer Res. 2013;19:1914.Google Scholar
  12. 12.
    Hsu CH, Lober RM, Li MD, Partap S, Murphy PA, Barnes PD, Fisher PG, Yeom KW. Decreased tumor apparent diffusion coefficient correlates with objective response of pediatric low-grade glioma to bevacizumab. J Neurooncol. 2015;122(3):491–6.CrossRefPubMedGoogle Scholar
  13. 13.
    Gururangan S, Fangusaro J, Poussaint TY, McLendon RE, Onar-Thomas A, Wu S, et al. Efficacy of bevacizumab plus irinotecan in children with recurrent low-grade gliomas—a Pediatric Brain Tumor Consortium study. Neuro Oncol. 2014;16(2):310–7.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Avery RA, Hwang EI, Jakacki RI, Packer RJ. Marked recovery of vision in children with optic pathway gliomas treated with bevacizumab. JAMA Ophthalmol. 2014;132(1):111–4.CrossRefPubMedGoogle Scholar
  15. 15.
    Venkatramani R, Malogolowkin MH, Mascarenhas L. Treatment of multiply relapsed wilms tumor with vincristine, irinotecan, temozolomide and bevacizumab. Pediatr Blood Cancer. 2014;61(4):756–9.CrossRefPubMedGoogle Scholar
  16. 16.
    Conde N, Cruz O, Albert A, Mora J. Antiangiogenic treatment as a pre-operative management of alveolar soft-part sarcoma. Pediatr Blood Cancer. 2011;57(6):1071–3.CrossRefPubMedGoogle Scholar
  17. 17.
    Voss SD, Glade-Bender J, Spunt SL, DuBois SG, Widemann BC, Park JR, et al. Growth plate abnormalities in pediatric cancer patients undergoing phase 1 anti-angiogenic therapy: a report from the Children’s Oncology Group Phase I Consortium. Pediatr Blood Cancer. 2015;62(1):45–51.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Federación de Sociedades Españolas de Oncología (FESEO) 2015

Authors and Affiliations

  • N. C. Millan
    • 1
  • M. J. Poveda
    • 1
  • O. Cruz
    • 1
  • J. Mora
    • 1
    Email author
  1. 1.Department of Pediatric Hematology and OncologyHospital Sant Joan de Déu de BarcelonaBarcelonaSpain

Personalised recommendations