A Bayesian Dose-finding Design for Oncology Clinical Trials of Combinational Biological Agents.

ABSTRACT: Treating patients with novel biological agents is becoming a leading trend in oncology. Unlike cytotoxic agents, for which efficacy and toxicity monotonically increase with dose, biological agents may exhibit non-monotonic patterns in their dose-response relationships. Using a trial with two biological agents as an example, we propose a dose-finding design to identify the biologically optimal dose combination (BODC), which is defined as the dose combination of the two agents with the highest efficacy and tolerable toxicity. A change-point model is used to reflect the fact that the dose-toxicity surface of the combinational agents may plateau at higher dose levels, and a flexible logistic model is proposed to accommodate the possible non-monotonic pattern for the dose-efficacy relationship.

SUBMITTER: Cai C 

PROVIDER: S-EPMC3913186 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature