TY - JOUR
T1 - New drugs for children and adolescents with cancer
T2 - The need for novel development pathways
AU - Vassal, Gilles
AU - Zwaan, C. Michel
AU - Ashley, David
AU - Le Deley, Marie Cecile
AU - Hargrave, Darren
AU - Blanc, Patricia
AU - Adamson, Peter C.
N1 - Funding Information:
Finally, improved preclinical models of childhood cancers are needed to prioritise agents in the clinical development pipeline. The Paediatric Preclinical Testing Programme 57 funded by the US National Cancer Institute provides one approach, and allows the study of new drugs in well characterised in-vitro cell lines and in-vivo xenografts. However, the predictive reliability of these models for targeted new agents remains unknown. New models, including orthotopic, transgenic, and ex-vivo three-dimensional approaches, 58 need further investment and investigation. The reinforcement of basic science and predictive, innovative, preclinical evaluation should be a major part of new oncology drug development for children.
Funding Information:
Early-phase development of paediatric cancer drugs differs substantially between the USA and Europe, in terms of regulatory requirements, structures, and governance. The US National Cancer Institute, through its Cancer Therapy Evaluation Programme, funds a 21-site consortium focused on paediatric phase 1 cancer trials that has supported trials directly, and also trials by industry collaborators. In Europe, an integrated research network of 42 centres in nine countries was created in 2003 to run early-phase trials sponsored by industry and academia and a target evaluation programme. 67 The Innovative Therapies for Children with Cancer consortium runs new drug trials through project funding from industry, national grants, and philanthropic organisations, but no sustainable European funding for infrastructure is available. This difference in public funding largely explains why almost ten times more early-phase trials are done in children in the USA than in Europe. Fiscal restrictions and limited access to early-phase trials are common in other regions such as Asia and Oceania. As a result, outside the USA, most children and adolescents with relapsed or refractory cancer do not have access to early clinical trials investigating innovative compounds. Some families travel to the USA so that their children can participate in clinical research, which can create enormous personal and financial burden.
PY - 2013/3/1
Y1 - 2013/3/1
N2 - Despite major progress in the past 40 years, 20% of children with cancer die from the disease, and 40% of survivors have late adverse effects. Innovative, safe, and effective medicines are needed. Although regulatory initiatives in the past 15 years in the USA and Europe have been introduced, new drug development for children with cancer is insufficient. Children and families face major inequity between countries in terms of access to innovative drugs in development. Hurdles and bottlenecks are well known-eg, small numbers of patients, the complexity of developing targeted agents and their biomarkers for selected patients, limitations of US and EU regulations for paediatric medicines, insufficient return on investment, and the global economic crisis facing drug companies. New drug development pathways could efficiently address the challenges with innovative methods and trial designs, investment in biology and preclinical research, new models of partnership and funding including public-private partnerships and precompetitive research consortia, improved regulatory requirements, initiatives and incentives that better address these needs, and increased collaboration between paediatric oncology cooperative groups worldwide. Increased cooperation between all stakeholders-academia, parents' organisations and advocacy groups, regulatory bodies, pharmaceutical companies, philanthropic organisations, and government-will be essential.
AB - Despite major progress in the past 40 years, 20% of children with cancer die from the disease, and 40% of survivors have late adverse effects. Innovative, safe, and effective medicines are needed. Although regulatory initiatives in the past 15 years in the USA and Europe have been introduced, new drug development for children with cancer is insufficient. Children and families face major inequity between countries in terms of access to innovative drugs in development. Hurdles and bottlenecks are well known-eg, small numbers of patients, the complexity of developing targeted agents and their biomarkers for selected patients, limitations of US and EU regulations for paediatric medicines, insufficient return on investment, and the global economic crisis facing drug companies. New drug development pathways could efficiently address the challenges with innovative methods and trial designs, investment in biology and preclinical research, new models of partnership and funding including public-private partnerships and precompetitive research consortia, improved regulatory requirements, initiatives and incentives that better address these needs, and increased collaboration between paediatric oncology cooperative groups worldwide. Increased cooperation between all stakeholders-academia, parents' organisations and advocacy groups, regulatory bodies, pharmaceutical companies, philanthropic organisations, and government-will be essential.
UR - http://www.scopus.com/inward/record.url?scp=84875246025&partnerID=8YFLogxK
U2 - 10.1016/S1470-2045(13)70013-5
DO - 10.1016/S1470-2045(13)70013-5
M3 - Review article
C2 - 23434337
AN - SCOPUS:84875246025
SN - 1470-2045
VL - 14
SP - e117-e124
JO - The Lancet Oncology
JF - The Lancet Oncology
IS - 3
ER -