TY - JOUR
T1 - Prognostic factors of overall survival in children and adolescents enrolled in dose-finding trials in Europe
T2 - An Innovative Therapies for Children with Cancer study
AU - Carceller, Fernando
AU - Bautista, Francisco J.
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 - Marshall, Lynley V.
AU - Vassal, Gilles
AU - Pearson, Andrew D.J.
AU - Geoerger, Birgit
AU - Moreno, Lucas
N1 - Publisher Copyright:
© 2016 Elsevier Ltd
PY - 2016/11/1
Y1 - 2016/11/1
N2 - OBJECTIVES: Dose-finding trials are fundamental to develop novel drugs for children and adolescents with advanced cancer. It is crucial to maximise individual benefit, whilst ensuring adequate assessment of key study end-points. We assessed prognostic factors of survival in paediatric phase I trials, including two predictive scores validated in adult oncology: the Royal Marsden Hospital (RMH) and the MD Anderson Cancer Center (MDACC) scores.METHODS: Data of patients with solid tumours aged <18 years at enrolment in their first dose-finding trial between 2000 and 2014 at eight centres of the Innovative Therapies for Children with Cancer European consortium were collected. Survival distributions were compared using log-rank test and Cox regression analyses.RESULTS: Overall, 248 patients were evaluated: median age, 11.2 years (range 1.0-17.9); 46% had central nervous system (CNS) tumours and 54% extra-CNS tumours. Complete responses were observed in 2.1%, partial responses in 7.2% and stable disease in 25.9%. Median overall survival (OS) was 6.3 months (95% confidence interval, 5.2-7.4). Lansky/Karnofsky ≤80%, no school/work attendance, elevated creatinine and RMH score ≥1 correlated with worse OS in the multivariate analysis. The RMH and MDACC scores correlated with OS in adolescents (12-17 years), p = 0.002, but not in children (2-11 years).CONCLUSIONS: Performance status of 90-100% and school/work attendance at enrolment are strong indicators of longer OS in paediatric phase I trials. Adult predictive scores correlate with survival in adolescents. These findings provide a useful orientation about potential prognosis and could lead in the future to more paediatric-adapted eligibility criteria in early-phase trials.
AB - OBJECTIVES: Dose-finding trials are fundamental to develop novel drugs for children and adolescents with advanced cancer. It is crucial to maximise individual benefit, whilst ensuring adequate assessment of key study end-points. We assessed prognostic factors of survival in paediatric phase I trials, including two predictive scores validated in adult oncology: the Royal Marsden Hospital (RMH) and the MD Anderson Cancer Center (MDACC) scores.METHODS: Data of patients with solid tumours aged <18 years at enrolment in their first dose-finding trial between 2000 and 2014 at eight centres of the Innovative Therapies for Children with Cancer European consortium were collected. Survival distributions were compared using log-rank test and Cox regression analyses.RESULTS: Overall, 248 patients were evaluated: median age, 11.2 years (range 1.0-17.9); 46% had central nervous system (CNS) tumours and 54% extra-CNS tumours. Complete responses were observed in 2.1%, partial responses in 7.2% and stable disease in 25.9%. Median overall survival (OS) was 6.3 months (95% confidence interval, 5.2-7.4). Lansky/Karnofsky ≤80%, no school/work attendance, elevated creatinine and RMH score ≥1 correlated with worse OS in the multivariate analysis. The RMH and MDACC scores correlated with OS in adolescents (12-17 years), p = 0.002, but not in children (2-11 years).CONCLUSIONS: Performance status of 90-100% and school/work attendance at enrolment are strong indicators of longer OS in paediatric phase I trials. Adult predictive scores correlate with survival in adolescents. These findings provide a useful orientation about potential prognosis and could lead in the future to more paediatric-adapted eligibility criteria in early-phase trials.
KW - Adolescents
KW - Children
KW - Dose-finding trial
KW - Innovative Therapies for Children with Cancer
KW - Phase I trial
KW - Prognostic factor
KW - Survival
UR - https://www.scopus.com/pages/publications/84988521847
U2 - 10.1016/j.ejca.2016.08.008
DO - 10.1016/j.ejca.2016.08.008
M3 - Article
C2 - 27662616
AN - SCOPUS:84988521847
SN - 0959-8049
VL - 67
SP - 130
EP - 140
JO - European Journal of Cancer
JF - European Journal of Cancer
ER -