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.