Abstract
In dose-finding trials of chemotherapeutic agents, the goal of identifying the maximum tolerated dose is usually determined by considering information on toxicity only, with the assumption that the highest safe dose also provides the most promising outlook for efficacy. Trials of molecularly targeted agents challenge accepted dose-finding methods because minimal toxicity may arise over all doses under consideration and higher doses may not result in greater response. In this article, we propose a new early-phase method for trials investigating targeted agents. We provide simulation results illustrating the operating characteristics of our design.
Keywords:
Continual reassessment method; Dose finding; Molecularly targeted agent; Optimal biological dose.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Algorithms
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Antineoplastic Agents / administration & dosage*
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Antineoplastic Agents / adverse effects
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Clinical Trials, Phase I as Topic / methods*
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Clinical Trials, Phase I as Topic / statistics & numerical data
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Clinical Trials, Phase II as Topic / methods*
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Clinical Trials, Phase II as Topic / statistics & numerical data
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Computer Simulation
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Data Interpretation, Statistical
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Dose-Response Relationship, Drug
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Drug Dosage Calculations
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Humans
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Maximum Tolerated Dose
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Models, Statistical
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Molecular Targeted Therapy* / adverse effects
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Molecular Targeted Therapy* / statistics & numerical data
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Neoplasms / drug therapy*
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Numerical Analysis, Computer-Assisted
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Research Design* / statistics & numerical data
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Treatment Outcome