title: Pediatric phase I trials in oncology: an analysis of study conduct efficiency.
abstract: OBJECTIVE
  To determine the efficacy and safety of pediatric phase I oncology trials in the era of dose-intensive chemotherapy and to analyze how efficiently these trials are conducted.
  
  
  METHODS
  Phase I pediatric oncology trials published from 1990 to 2004 and their corresponding adult phase I trials were reviewed. Dose escalation schemes using fixed 30% dose increments were studied to theoretically determine whether trials could be completed utilizing fewer patients and dose levels.
  
  
  RESULTS
  Sixty-nine pediatric phase I oncology trials enrolling 1,973 patients were identified. The pediatric maximum-tolerated dose (MTD) was strongly correlated with the adult MTD (r = 0.97). For three-fourths of the trials, the pediatric and adult MTD differed by no more than 30%, and for more than 85% of the trials, the pediatric MTD was less than or equal to 1.6 times the adult MTD. The median number of dose levels studied was four (range, two to 13). The overall objective response rate was 9.6%, the likelihood of experiencing a dose-limiting toxicity was 24%, and toxic death rate was 0.5%.
  
  
  CONCLUSIONS
  Despite the strong correlation between the adult and pediatric MTDs, more than four dose levels were studied in 40% of trials. There appeared to be little value in exploring dose levels greater than 1.6 times the adult MTD. Limiting pediatric phase I trials to a maximum of four doses levels would significantly shorten the timeline for study conduct without compromising safety.
authors.affiliation: Division of Clinical Pharmacology & Therapeutics, The Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
authors.forename: Debra P
authors.initials: DP
authors.lastname: Lee
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Skolnik
authors.forename: Peter C
authors.initials: PC
authors.lastname: Adamson
mesh_terms: D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D002648:Child; D017321:Clinical Trials, Phase I as Topic; D004334:Drug Administration Schedule; D006801:Humans; D020714:Maximum Tolerated Dose; D008657:Metabolic Clearance Rate; D009369:Neoplasms / Q000188:drug therapy*; D012449:Safety; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents