A semi-mechanistic dose-finding design in oncology using pharmacokinetic/pharmacodynamic modeling.

ABSTRACT: While a number of phase I dose-finding designs in oncology exist, the commonly used ones are either algorithmic or empirical model-based. We propose a new framework for modeling the dose-response relationship, by systematically incorporating the pharmacokinetic (PK) data collected in the trial and the hypothesized mechanisms of the drug effects, via dynamic PK/PD modeling, as well as modeling of the relationship between a latent cumulative pharmacologic effect and a binary toxicity outcome. This modeling framework naturally incorporates the information on the impact of dose, schedule and method of administration (e.g., drug formulation and route of administration) on toxicity. The resulting design is an extension of existing designs that make use of pre-specified summary PK information (su

SUBMITTER: Su X 

PROVIDER: S-EPMC10134386 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature