Dose-Finding with Two Agents in Phase I Oncology Trials
We propose an adaptive two-stage Bayesian design for finding one or more acceptable dose combinations of two cytotoxic agents used together in a Phase I clinical trial. The method requires that each of the two agents has been studied previously as a single agent, which is almost invariably the case in practice. A parametric model is assumed for the probability of toxicity as a function of the two doses. Informative priors for parameters characterizing the single-agent toxicity probability curves are either elicited from the physician(s) planning the trial or obtained from historical data, and vague priors are assumed for parameters characterizing two-agent interactions. A method for eliciting the single-agent parameter priors is described. The design is applied to a trial of gemcitabine and cyclophosphamide, and a simulation study is presented.
Document Type: Research Article
Affiliations: 1: Department of Biostatistics, Box 447, University of Texas, M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas 77030, U.S.A. 2: Department of Genitourinary Medical Oncology, Box 422, University of Texas, M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas 77030, U.S.A.
Publication date: September 1, 2003