Evaluation of Fixed Dosing of New Anticancer Agents in Phase I Studies

Abstract

Aim: To assess the basis of dosage of investigational anticancer agents in adult phase I trials. Materials and Methods: All nonpediatric phase I trials presented at the meetings of the American Society of Clinical Oncology and of the American Society of Hematology in 2005 were reviewed. Data regarding the type of investigational agent, the route of administration and the basis of dosing (fixed, body surface area, body weight) were collected. Results: In all, 225 phase I studies were analyzed concerning 148 new anticancer agents. Among 225 studies, 91 (40.4%) used a fixed dose. Dosages were adjusted to body surface area and body weight in 44% (99/225) and 13.8% (31/225) of all trials, respectively. Regarding drugs given orally (n=40), the majority of the trials (62/77; 80%) used a fixed dose. By contrast, only 7.5% (9/120) of studies involving intravenous agents (n=82) were conducted with a fixed dose. Most of these trials (71.6%) used a dose adjusted to body surface area. Of the 73 trials involving conventional cytotoxics, 70 (96%) used body surface area dosing. On the other hand, 78.5% (62/79) of studies investigating targeted agents used a fixed dose. Monoclonal antibodies and antisense agents were mainly administered on a body weight basis (13/25 and 4/7 trials, respectively). Conclusion: A fixed dose was used in a minority of the adult phase I trials presented at the ASCO and ASH meetings in 2005.