Bayesian modeling of a bivariate toxicity outcome for early phase oncology trials evaluating dose regimens.

ABSTRACT: Most phase I trials in oncology aim to find the maximum tolerated dose (MTD) based on the occurrence of dose limiting toxicities (DLT). Evaluating the schedule of administration in addition to the dose may improve drug tolerance. Moreover, for some molecules, a bivariate toxicity endpoint may be more appropriate than a single endpoint. However, standard dose-finding designs do not account for multiple dose regimens and bivariate toxicity endpoint within the same design. In this context, following a phase I motivating trial, we proposed modeling the first type of DLT, cytokine release syndrome, with the entire dose regimen using pharmacokinetics and pharmacodynamics (PK/PD), whereas the other DLT (DLT_o ) was modeled with the cumulative dose. We developed three approaches to model

SUBMITTER: Gerard E 

PROVIDER: S-EPMC9292544 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature