Prognostic factors of overall survival in children and adolescents enrolled in dose-finding trials in Europe: An Innovative Therapies for Children with Cancer study

Fernando Carceller, Francisco J. 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, Lynley V. Marshall, Gilles Vassal, Andrew D J Pearson, Birgit Geoerger, Lucas Moreno

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)130-140
Number of pages11
JournalEuropean Journal of Cancer
Volume67
DOIs
Publication statusPublished - Nov 1 2016

Fingerprint

Investigational Therapies
Survival
Neoplasms
Central Nervous System Neoplasms
Pediatrics
Creatinine
Multivariate Analysis
Regression Analysis
Confidence Intervals
Pharmaceutical Preparations

Keywords

  • Adolescents
  • Children
  • Dose-finding trial
  • Innovative Therapies for Children with Cancer
  • Phase I trial
  • Prognostic factor
  • Survival

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Prognostic factors of overall survival in children and adolescents enrolled in dose-finding trials in Europe : An Innovative Therapies for Children with Cancer study. / Carceller, Fernando; Bautista, Francisco J.; Jiménez, Irene; Hladun-Álvaro, Raquel; Giraud, Cécile; Bergamaschi, Luca; Dandapani, Madhumita; Aerts, Isabelle; Doz, François; Frappaz, Didier; Casanova, Michela; Morland, Bruce; Hargrave, Darren R.; Marshall, Lynley V.; Vassal, Gilles; Pearson, Andrew D J; Geoerger, Birgit; Moreno, Lucas.

In: European Journal of Cancer, Vol. 67, 01.11.2016, p. 130-140.

Research output: Contribution to journalArticle

Carceller, F, Bautista, FJ, Jiménez, I, Hladun-Álvaro, R, Giraud, C, Bergamaschi, L, Dandapani, M, Aerts, I, Doz, F, Frappaz, D, Casanova, M, Morland, B, Hargrave, DR, Marshall, LV, Vassal, G, Pearson, ADJ, Geoerger, B & Moreno, L 2016, 'Prognostic factors of overall survival in children and adolescents enrolled in dose-finding trials in Europe: An Innovative Therapies for Children with Cancer study', European Journal of Cancer, vol. 67, pp. 130-140. https://doi.org/10.1016/j.ejca.2016.08.008
Carceller, Fernando ; Bautista, Francisco J. ; Jiménez, Irene ; Hladun-Álvaro, Raquel ; Giraud, Cécile ; Bergamaschi, Luca ; Dandapani, Madhumita ; Aerts, Isabelle ; Doz, François ; Frappaz, Didier ; Casanova, Michela ; Morland, Bruce ; Hargrave, Darren R. ; Marshall, Lynley V. ; Vassal, Gilles ; Pearson, Andrew D J ; Geoerger, Birgit ; Moreno, Lucas. / Prognostic factors of overall survival in children and adolescents enrolled in dose-finding trials in Europe : An Innovative Therapies for Children with Cancer study. In: European Journal of Cancer. 2016 ; Vol. 67. pp. 130-140.
@article{782db087ddc14c1ea41721794b79ae4f,
title = "Prognostic factors of overall survival in children and adolescents enrolled in dose-finding trials in Europe: An Innovative Therapies for Children with Cancer study",
abstract = "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.",
keywords = "Adolescents, Children, Dose-finding trial, Innovative Therapies for Children with Cancer, Phase I trial, Prognostic factor, Survival",
author = "Fernando Carceller and Bautista, {Francisco J.} and Irene Jim{\'e}nez and Raquel Hladun-{\'A}lvaro and C{\'e}cile Giraud and Luca Bergamaschi and Madhumita Dandapani and Isabelle Aerts and Fran{\cc}ois Doz and Didier Frappaz and Michela Casanova and Bruce Morland and Hargrave, {Darren R.} and Marshall, {Lynley V.} and Gilles Vassal and Pearson, {Andrew D J} and Birgit Geoerger and Lucas Moreno",
year = "2016",
month = "11",
day = "1",
doi = "10.1016/j.ejca.2016.08.008",
language = "English",
volume = "67",
pages = "130--140",
journal = "European Journal of Cancer",
issn = "0959-8049",
publisher = "Elsevier Ltd",

}

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

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 - http://www.scopus.com/inward/record.url?scp=84988521847&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84988521847&partnerID=8YFLogxK

U2 - 10.1016/j.ejca.2016.08.008

DO - 10.1016/j.ejca.2016.08.008

M3 - Article

AN - SCOPUS:84988521847

VL - 67

SP - 130

EP - 140

JO - European Journal of Cancer

JF - European Journal of Cancer

SN - 0959-8049

ER -