부산대학교 도서관

2518 Background: New drug development is a time- and resource-consuming process. Phase 1 trials constitute a major key- step of this development. Shortening the accrual time may improve this process.Methods: 292 published phase-1-trials were retrospectively reviewed to establish the determinants of accrual period of time (APT) using Log-rank test and then Cox Model.Results: Out of 292 trials (1997-2008), only 107 reports (36%) described the accrual time (median: 20 months, 5-72). Phase-2- recommended dose was established in 87 studies (81%). Most of studies investigated regimens included cytotoxic drugs (77%) or molecular targeted therapies (29%). Most of parameters did not significantly affect the APT: nature and number of investigated drugs, duration of treatment cycle, phase 1 dedicated to specific tumoral subtypes, number of centers, method of drug escalation (classical 3+3 vs. accelerated titration design), type of dose increment (modified Fibonacci method vs. others) and presence of expanded cohort at the phase-II-recommended dose. Under univariate analysis, two parameters shortened the APT: studies conducted in USA vs. other place (19 vs. 21 months, p=0.03) and regimen with more than 2 dose-escalated drugs (13 vs. 21 months, p=0.003). One parameter was significantly associated with longer APT: starting dose justified by animal toxicology data (first-in-man studies) vs. previous clinical trials (22 vs. 19 months, p=0.03). Cox model analysis retained only one determinant: starting dose justified by animal toxicology data: HR=4.07 [1.45- 11.42], p=0.047.Conclusions: Few parameters influence the APT in the dose-escalation phase-1 setting. Real first-in-man phase 1 studies based on starting dose estimated from animal toxicological data require longer APT. [Table: see text].