Designing phase I oncology dose escalation using dose-exposure-toxicity models as a complementary approach to model-based dose-toxicity models.

ABSTRACT: One of the objectives of oncology phase I dose-escalation studies has been to determine the maximum tolerated dose (MTD). Although MTD is no longer set as the dose for further development in contemporary oncology drug development, MTD determination is still important for informing the therapeutic index. Bayesian adaptive model-based designs are becoming mainstream in oncology first-in-human trials. Herein, we illustrate via simulations the use of systemic exposure in Bayesian adaptive dose-toxicity models to estimate MTD. We extend traditional dose-toxicity models to incorporate pharmacokinetic exposure, which provides information on exposure-toxicity relationships. We pursue dose escalation until the maximum tolerated exposure (corresponding to the MTD) is reached. By leveraging pharmacok

SUBMITTER: Pantoja K 

PROVIDER: S-EPMC9574748 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature