Pediatric drug development: a perspective from the Cancer Therapy Evaluation Program (CTEP) of the National Cancer Institute (NCI).

Well-designed and carefully conducted pediatric phase 1 trials are critical to the process of evaluating new agents for potential benefit in children with cancer, and the National Cancer Institute (NCI) has for a number of years sponsored pediatric phase I trials. The development of new agents for children with cancer differs in important ways from drug development for adults with cancer, primarily necessitated by the smaller number of children eligible for phase I trials in comparison to adults. Pediatric drug development is characterized by a greater need to prioritize new agents for evaluation, since many more agents can be evaluated in adults than can be evaluated in children. Pediatric phase I trials are also commonly conducted as multi-institutional collaborations, since most single institutions do not have enough eligible patients to complete phase I trials within a reasonable time. In addition, pediatric phase I trials begin at doses close to the adult maximum tolerated dose, thereby minimizing the number of patients required to complete pediatric phase I trials. While pediatric phase I trials have traditionally evaluated conventional cytotoxic agents, new classes of agents with distinctive mechanisms of action are entering clinical evaluation. These agents target specific cellular proteins (e.g., protein tyrosine kinases, protein kinase C isoforms, enzymes involved in controlling progression through the cell cycle). Determining whether these agents with specificity for critical cellular proteins will be effective anti-cancer agents will be an important objective of pediatric clinical investigations in the coming years.