title: Conduct of phase I trials in children with cancer.
abstract: OBJECTIVE
  Future progress in the care of children with cancer requires appropriate evaluations of promising new agents for pediatric indications, beginning with well-conducted phase I trials. This report summarizes current guidelines for the conduct of pediatric phase I trials and represents a consensus between American and European investigators. The primary objective of pediatric phase I trials is to define safe and appropriate doses and schedules of new agents that can subsequently be used in phase II trials to test for activity against specific childhood malignancies. Prioritization of agents for evaluation in children is critical, since many more investigational agents are evaluated in adult patients than can be systematically evaluated in children. Considerations used in prioritizing agents include activity in xenograft models, novel mechanism of action, favorable drug-resistance profile, and activity observed in adult trials of the agent.
  
  
  CONCLUSIONS
  Distinctive characteristics of pediatric phase I trials, in comparison to adult phase I trials, include the necessity for multiinstitutional participation and their higher starting dose (typically 80% of the adult maximum-tolerated dose [MTD]), both of which reflect the relative unavailability of appropriate patients. The application of uniform eligibility criteria and standard definitions for MTD and dose-limiting toxicity (DLT) help to assure that pediatric phase I trials are safely conducted and reliably identify appropriate doses and schedules of agents for phase II evaluation. Where possible, pediatric phase I trials also define the pharmacokinetic behavior of new agents in children.
authors.affiliation: Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD 20892, USA. smithm@ctep.nci.nih.gov
authors.forename: M
authors.initials: M
authors.lastname: Smith
authors.forename: M
authors.initials: M
authors.lastname: Bernstein
authors.forename: W A
authors.initials: WA
authors.lastname: Bleyer
authors.forename: J D
authors.initials: JD
authors.lastname: Borsi
authors.forename: P
authors.initials: P
authors.lastname: Ho
authors.forename: I J
authors.initials: IJ
authors.lastname: Lewis
authors.forename: A
authors.initials: A
authors.lastname: Pearson
authors.forename: F
authors.initials: F
authors.lastname: Pein
authors.forename: C
authors.initials: C
authors.lastname: Pratt
authors.forename: G
authors.initials: G
authors.lastname: Reaman
authors.forename: R
authors.initials: R
authors.lastname: Riccardi
authors.forename: N
authors.initials: N
authors.lastname: Seibel
authors.forename: R
authors.initials: R
authors.lastname: Trueworthy
authors.forename: R
authors.initials: R
authors.lastname: Ungerleider
authors.forename: G
authors.initials: G
authors.lastname: Vassal
authors.forename: T
authors.initials: T
authors.lastname: Vietti
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D017321:Clinical Trials, Phase I as Topic / Q000592:standards*; D017408:Guidelines as Topic; D006801:Humans; D007223:Infant; D009369:Neoplasms / Q000628:therapy*
chemical_list: D000970:Antineoplastic Agents