Dose-Finding With Two Agents In Phase I Trials

In this paper, the author want to probe the method how to find one or more acceptable drug dose combinations of two agents used together in a Phase I clinical trial. For single agent, finding the maximal tolerated dose (MTD), people have many successful methods, such as "continual reassessment method" (CRM), and "Up and down". Yet for two or several agents , we have to study more successful method. American Peter .F. Thall and some people try one complicated model to solve this problem , their method have very complex compute progress, so it is not easy to apply it actually. The author have a ideal of simplify this model and made it have a simply compute progress , so we research their method . Based their work , the author 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 invariable 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 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 phosphamid, and a simulation study is presented.