Finding Maximum Tolerated Dose in Phase I Oncology Clinical Trials with Bayesian Methods

Abstract

Maximum tolerated dose (MTD) is a maximal amount of drug or radiation re- sulting relatively acceptable dose-limiting toxicity (DLT). Accurate value of MTD should be found in Phase I trials in order to create the possibility to conduct successful Phase II (pilot efficacy and safety evaluation) and Phase III (comparative efficacy) trials. The aim of this paper is to review the difficulties of the dose-finding methods including multi-agent problems and late-onset toxicities, and to discuss Bayesian adaptive dose-finding methods which can handle these issues.