New Adaptive Method for Phase I Trials in Oncology

Assessment of the maximum tolerated dose for a small sample of patients is the objective of phase I trials in oncology. We propose a new adaptive approach performing differentiation of each type of toxicity and their grades, definition of the dose‐limiting toxicity as a logical combination of toxicity events, modeling of the risk of toxic events as a function of the drug dose, and integration of individual covariates. An application study with retrospective data from a phase I Taxol pediatric trial revealed age as an influential covariate, allowing individualization of a patient's maximum tolerated dose. A simulation study illustrates the practice of sequential inclusion of patients, of constraints in the dose‐finding process and of trial stopping rules. The approach presented here allows quick maximum tolerated dose assessment with a small sample of patients and assists the design of phase I trials in oncology.

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