Lessons learned from adult clinical experience to inform evaluations of VEGF pathway inhibitors in children with cancer

Pediatr Blood Cancer. 2014 Aug;61(8):1497-505. doi: 10.1002/pbc.25036. Epub 2014 Apr 24.

Abstract

Agents targeting the vascular endothelial growth factor (VEGF) pathway have been studied in adults with cancer for nearly two decades. It is important to assess the lessons learned from this adult experience and to see how these lessons can help inform pediatric development of agents in this class. The benefit achieved from the use of VEGF pathway targeted agents for adult cancers has primarily been to delay for several months disease progression and less commonly time to death for conditions in which cure is not a reasonable expectation. VEGF pathway targeted agents have shown no efficacy when applied in the adjuvant setting. For adults with advanced cancer, prolongation of survival by 2-3 months is considered an important achievement in some settings. However, the primary goal of pediatric oncology clinical research is to identify treatments that allow children to be cured of their cancer and to grow to adulthood without treatment-induced limitations that lower their quality of survival. An important question for the pediatric oncology research community, pharmaceutical companies, and regulatory agencies to address in planning for future clinical trials is whether existing data support a role for VEGF pathway targeted agents in contributing to a therapeutic pathway to cure for children with cancer.

Keywords: anti-angiogenesis; kinase inhibitors; vascular endothelial growth factor.

MeSH terms

  • Adolescent
  • Adult
  • Angiogenesis Inhibitors / therapeutic use*
  • Child
  • Child, Preschool
  • Disease-Free Survival
  • Humans
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Neoplasms / mortality
  • Neovascularization, Pathologic / drug therapy*
  • Neovascularization, Pathologic / mortality
  • Neovascularization, Pathologic / pathology
  • Survival Rate
  • Vascular Endothelial Growth Factor A / metabolism*

Substances

  • Angiogenesis Inhibitors
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A