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A Bayesian adaptive design for estimating the maximum tolerated dose curve using drug combinations in cancer phase I clinical trials.


ABSTRACT: We present a cancer phase I clinical trial design of a combination of two drugs with the goal of estimating the maximum tolerated dose curve in the two-dimensional Cartesian plane. A parametric model is used to describe the relationship between the doses of the two agents and the probability of dose limiting toxicity. The model is re-parameterized in terms of the probabilities of toxicities at dose combinations corresponding to the minimum and maximum doses available in the trial and the interaction parameter. Trial design proceeds using cohorts of two patients receiving doses according to univariate escalation with overdose control (EWOC), where at each stage of the trial, we seek a dose of one agent using the current posterior distribution of the MTD of this agent given the current dose

SUBMITTER: Tighiouart M 

PROVIDER: S-EPMC5055414 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature