Characteristics and outcome of pediatric patients enrolled in phase I oncology trials

Oncologist. 2008 Jun;13(6):679-89. doi: 10.1634/theoncologist.2008-0046.


Purpose: 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.

Experimental design: 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.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Child
  • Child, Preschool
  • Clinical Trials, Phase I as Topic*
  • Combined Modality Therapy
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Infant
  • Male
  • Neoplasm Recurrence, Local / diagnosis
  • Neoplasm Recurrence, Local / therapy*
  • Neoplasms / diagnosis
  • Neoplasms / therapy*
  • Patient Participation
  • Prognosis
  • Radiotherapy Dosage
  • Retrospective Studies
  • Stem Cell Transplantation
  • Survival Rate
  • Treatment Outcome