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


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.

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Ms Carole Lecinse, Innovative Therapies for Children with Cancer (ITCC) and Ms Gynette Cook, The Royal Marsden NHS Foundation Trust. This work was supported by the ITCC infrastructure. Additionally, F.C. holds a senior fellowship funded by the National Institute for Health Research Biomedical Research Centre (BRC) at the Royal Marsden and by the Sohn Foundation. I.J. holds a fellowship funded by the Nelia et Amadeo Barletta Foundation. D.H. is supported by the BRC at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London. A.D.J.P. was supported by Cancer Research UK (CRUK): programme grant C1178/A10294 - Chair in Pediatric Oncology. L.Mo. is funded by the Juan Rodés senior fellowship from Instituto de Salud Carlos III. L.V.M. is funded by the Oak Foundation (Grant OCay-04-169).

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Correspondence to Fernando Carceller.

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Conflict of interest

These results were presented in part at the International Symposium of Pediatric Neuro-Oncology (ISPNO) held in June 2016. I.J. acknowledges travel/accommodation expenses from MSD. F.D. has had a consulting role for Novartis and travel/accommodation expenses from Novartis. M.C. has had a consulting role for Novartis, Boehringer and Roche. D.H. has had a consulting role for Roche, Astra Zeneca, Boehringer, GSK and Thrombogenics, received honoraria from Roche, Astra Zeneca and Boehringer, and travel/accommodation expenses from Roche, Astra Zeneca, Boehringer, GSK, Thrombogenics and Merck. L.V.M. has had a consulting role for Astra Zeneca, GSK, Novartis and Eli Lilly. A.D.J.P. has received honoraria from Astra Zeneca, Boehringer and Novartis. L.Mo. has had a consulting role for Novartis, Astra Zeneca and Roche. All other authors declare no conflicts of interest to disclose.

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Carceller, F., Bautista, F., Jiménez, I. et al. Outcome of children and adolescents with central nervous system tumors in phase I trials. J Neurooncol 137, 83–92 (2018).

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  • Targeted drugs
  • Children
  • Adolescents
  • Central nervous system tumor
  • Brain tumor
  • Phase I trial