Outcome of children and adolescents with central nervous system tumors in phase I trials

J Neurooncol. 2018 Mar;137(1):83-92. doi: 10.1007/s11060-017-2698-z. Epub 2017 Dec 13.


Central nervous system (CNS) tumors are a leading cause of death in pediatric oncology. New drugs are desperately needed to improve survival. We evaluated the outcome of children and adolescents with CNS tumors participating in phase I trials within the Innovative Therapies for Children with Cancer (ITCC) consortium. Patients with solid tumors aged < 18 years at enrollment in their first dose-finding trial between 2000 and 2014 at eight ITCC centers were included retrospectively. Survival was evaluated using univariate/multivariate analyses. Overall, 114 patients were included (109 evaluable for efficacy). Median age was 10.2 years (range 1.0-17.9). Main diagnoses included: medulloblastoma/primitive neuroectodermal tumors (32.5%) and high-grade gliomas (23.7%). Complete/partial responses (CR/PR) were reported in 7.3% patients and stable disease (SD) in 23.9%. Performance status of 90-100%, school/work attendance, normal ALT/AST and CR/PR/SD correlated with better overall survival (OS) in the univariate analysis. No variables assessable at screening/enrollment were associated with OS in the multivariate analysis. Five patients (4.5%) were discontinued from study due to toxicity. No toxic deaths occurred. Median OS was 11.9 months with CR/PR, 14.5 months with SD and 3.7 months with progressive disease (p < 0.001). The enrollment of children and adolescents with CNS tumors in phase I trials is feasible, safe and offers potential benefit for the patients. Sustained disease stabilization has a promising role as a marker of anti-tumor activity in children with CNS tumors participating in phase I trials.

Keywords: Adolescents; Brain tumor; Central nervous system tumor; Children; Phase I trial; Targeted drugs.

MeSH terms

  • Adolescent
  • Central Nervous System Neoplasms / diagnosis
  • Central Nervous System Neoplasms / therapy*
  • Child
  • Child, Preschool
  • Clinical Trials, Phase I as Topic
  • Disease Progression
  • Female
  • Humans
  • Infant
  • Kaplan-Meier Estimate
  • Male
  • Outcome Assessment, Health Care
  • Treatment Outcome