title: New adaptive method for phase I trials in oncology.
abstract: 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.
authors.affiliation: Department of Pharmacokinetics, Faculty of Pharmacy, University of Mèditerranèe, Marseilles, France. cmeille@pharmacie.univ-mrs.fr
authors.forename: C
authors.initials: C
authors.lastname: Meille
authors.forename: J C
authors.initials: JC
authors.lastname: Gentet
authors.forename: D
authors.initials: D
authors.lastname: Barbolosi
authors.forename: N
authors.initials: N
authors.lastname: André
authors.forename: F
authors.initials: F
authors.lastname: Doz
authors.forename: A
authors.initials: A
authors.lastname: Iliadis
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D017321:Clinical Trials, Phase I as Topic / Q000379:methods* / Q000639:trends; D006801:Humans; D020714:Maximum Tolerated Dose; D008495:Medical Oncology / Q000379:methods* / Q000639:trends; D008954:Models, Biological; D012189:Retrospective Studies
chemical_list: D000970:Antineoplastic Agents