title: Characteristics and outcome of pediatric patients enrolled in phase I oncology trials.
abstract: OBJECTIVE
  To describe the characteristics of pediatric subjects who enroll in phase I trials, to determine the associations between pre-enrollment characteristics and the risk for toxicity, and to analyze response and survival outcomes.
  
  
  METHODS
  Pre-enrollment characteristics and study outcomes were retrospectively analyzed for children with refractory solid tumors treated in one of 16 phase I trials with similar eligibility criteria at the National Cancer Institute between 1992 and 2005.
  
  
  RESULTS
  The 262 subjects analyzed had received a median of two (range, 0-9) prior chemotherapy regimens, and were on one (range, 0-12) concomitant medication. The Eastern Cooperative Oncology Group performance status scores for subjects were 0 (29%), 1 (48%), and 2 (19%); 19% had received a prior stem cell transplantation and 73% had received prior radiation. Approximately 90% of subjects were evaluable for the primary trial endpoints (toxicity and pharmacokinetics). Seventeen percent of subjects experienced a dose-limiting toxicity (DLT), 5% discontinued the study drug because of toxicity, and a drug-related death occurred in one subject (0.4%). Variables associated with a higher risk for developing a DLT, by multiple logistic regression analysis, were drug dose and prior radiation, for myelosuppressive agents, and drug dose and performance status, for nonmyelosuppressive agents. The complete and partial response rate was 4%; however, 17% of subjects had stable disease (received three or more cycles). The median overall survival time from the time of enrollment was five months.
  
  
  CONCLUSIONS
  Primary trial objectives are achieved in approximately 90% of subjects with the standard phase I trial design and eligibility criteria despite the intensification of frontline and salvage therapies in pediatric subjects with cancer.
authors.affiliation: Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, 10 Center Drive, Building 10-CRC, Room 1-3872, Bethesda, MD 20892, USA. kimaer@mail.nih.gov
authors.forename: Aerang
authors.initials: A
authors.lastname: Kim
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Fox
authors.forename: Katherine
authors.initials: K
authors.lastname: Warren
authors.forename: Susan M
authors.initials: SM
authors.lastname: Blaney
authors.forename: Stacey L
authors.initials: SL
authors.lastname: Berg
authors.forename: Peter C
authors.initials: PC
authors.lastname: Adamson
authors.forename: Madeleine
authors.initials: M
authors.lastname: Libucha
authors.forename: Elena
authors.initials: E
authors.lastname: Byrley
authors.forename: Frank M
authors.initials: FM
authors.lastname: Balis
authors.forename: Brigitte C
authors.initials: BC
authors.lastname: Widemann
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D017321:Clinical Trials, Phase I as Topic; D003131:Combined Modality Therapy; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000628:therapy*; D009369:Neoplasms / Q000175:diagnosis / Q000628:therapy*; D010358:Patient Participation; D011379:Prognosis; D011879:Radiotherapy Dosage; D012189:Retrospective Studies; D033581:Stem Cell Transplantation; D015996:Survival Rate; D016896:Treatment Outcome