DESIGN AND RESULTS OF PHASE-I CANCER CLINICAL-TRIALS - 3-YEAR EXPERIENCE AT MD-ANDERSON-CANCER-CENTER

Purpose: Alternatives to the standard design for conducting phase I tr ials are proposed with increasing frequency. This study was undertaken to determine how phase I trials ore currently conducted and to provid e a basis for evaluation of evolving methodology. Subjects and Methods : All published phase I trials from a single institution over a 3-year period were reviewed to determine the method of selection of the reco mmended dose for a phase II trial of a new agent, type and extent of t oxicity, number of patients treated at the recommended dose, and clini cal response. Results: All 23 published trials used the standard metho d of entering cohorts of patients at increasing dose levels and observ ing toxic effects to determine the dose recommended for phose II study . Among 610 patients, 26% were treated at or within 10% of the recomme nded dose and 35% were treated with less than 50% of the recommended d ose or on a trial that yielded no recommended dose, Among is trials us ing agents previously tested in humans, fewer patients were treated at much less than the recommended dose, For trials in which myelosuppres sion was dose-limiting, the estimated probability of serious myelosupp ression associated with the recommended dose ranged from 23% to 66%, N ineteen patients (3%) responded to therapy. Conclusion: This summary o f phase I trials recently conducted at M.D. Anderson Cancer Center con firms the need for alternative methods, provides baseline information against which alternatively conducted trials can be compared, and demo nstrates some practical clinical trial issues not generally considered when alternative methods are proposed. (C) 1996 by American Society o f Clinical Oncology.