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

Fernando Carceller, Francisco Bautista, Irene Jiménez, Raquel Hladun-Álvaro, Cécile Giraud, Luca Bergamaschi, Madhumita Dandapani, Isabelle Aerts, François Doz, Didier Frappaz, Michela Casanova, Bruce Morland, Darren R Hargrave, Gilles Vassal, Andrew D J Pearson, Birgit Geoerger, Lucas Moreno, Lynley V Marshall

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Abstract

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.

Original languageEnglish
Pages (from-to)83-92
Number of pages10
JournalJournal of Neuro-Oncology
Volume137
Issue number1
DOIs
Publication statusPublished - Mar 2018

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Carceller, F., Bautista, F., Jiménez, I., Hladun-Álvaro, R., Giraud, C., Bergamaschi, L., Dandapani, M., Aerts, I., Doz, F., Frappaz, D., Casanova, M., Morland, B., Hargrave, D. R., Vassal, G., Pearson, A. D. J., Geoerger, B., Moreno, L., & Marshall, L. V. (2018). Outcome of children and adolescents with central nervous system tumors in phase I trials. Journal of Neuro-Oncology, 137(1), 83-92. https://doi.org/10.1007/s11060-017-2698-z