TY - JOUR
T1 - Outcome of children and adolescents with central nervous system tumors in phase I trials
AU - Carceller, Fernando
AU - Bautista, Francisco
AU - Jiménez, Irene
AU - Hladun-Álvaro, Raquel
AU - Giraud, Cécile
AU - Bergamaschi, Luca
AU - Dandapani, Madhumita
AU - Aerts, Isabelle
AU - Doz, François
AU - Frappaz, Didier
AU - Casanova, Michela
AU - Morland, Bruce
AU - Hargrave, Darren R.
AU - Vassal, Gilles
AU - Pearson, Andrew D.J.
AU - Geoerger, Birgit
AU - Moreno, Lucas
AU - Marshall, Lynley V.
N1 - Publisher Copyright:
© 2017, Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2018/3/1
Y1 - 2018/3/1
N2 - 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.
AB - 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.
KW - Adolescents
KW - Brain tumor
KW - Central nervous system tumor
KW - Children
KW - Phase I trial
KW - Targeted drugs
UR - https://www.scopus.com/pages/publications/85037982525
U2 - 10.1007/s11060-017-2698-z
DO - 10.1007/s11060-017-2698-z
M3 - Article
C2 - 29236237
AN - SCOPUS:85037982525
SN - 0167-594X
VL - 137
SP - 83
EP - 92
JO - Journal of Neuro-Oncology
JF - Journal of Neuro-Oncology
IS - 1
ER -