Bayesian dose-finding designs for combination of molecularly targeted agents assuming partial stochastic ordering.

ABSTRACT: Molecularly targeted agent (MTA) combination therapy is in the early stages of development. When using a fixed dose of one agent in combinations of MTAs, toxicity and efficacy do not necessarily increase with an increasing dose of the other agent. Thus, in dose-finding trials for combinations of MTAs, interest may lie in identifying the optimal biological dose combinations (OBDCs), defined as the lowest dose combinations (in a certain sense) that are safe and have the highest efficacy level meeting a prespecified target. The limited existing designs for these trials use parametric dose-efficacy and dose-toxicity models. Motivated by a phase I/II clinical trial of a combination of two MTAs in patients with pancreatic, endometrial, or colorectal cancer, we propose Bayesian dose-finding desig

SUBMITTER: Guo B 

PROVIDER: S-EPMC4359011 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature