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 toxici...

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Bibliographic Details
Published in:Clinical pharmacology and therapeutics 2008-06, Vol.83 (6), p.873-881
Main Authors: Meille, C, Gentet, JC, Barbolosi, D, André, N, Doz, F, Iliadis, A
Format: Article
Language:English
Subjects:
Antineoplastic Agents - administration & dosage
Antineoplastic Agents - therapeutic use
Biological and medical sciences
Clinical Trials, Phase I as Topic - methods
Clinical Trials, Phase I as Topic - trends
Humans
Maximum Tolerated Dose
Medical Oncology - methods
Medical Oncology - trends
Medical sciences
Models, Biological
Pharmacology. Drug treatments
Retrospective Studies
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Summary: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. Clinical Pharmacology & Therapeutics (2008); 83, 6, 873–881 doi:10.1038/sj.clpt.6100383
ISSN:0009-9236
1532-6535
DOI:10.1038/sj.clpt.6100383