• Philip S Boonstra, Jincheng Shen, Jeremy M G Taylor, Thomas M Braun, Kent A Griffith, Stephanie Daignault, Gregory P Kalemkerian, Theodore S Lawrence, and Matthew J Schipper.
• Departments of Biostatistics (PSB, JS, JMGT, TMB, KAG, SD, MJS), Internal Medicine (GPK), Radiation Oncology (JMGT, TSL, MJS), University of Michigan. philb@umich.edu.
• J. Natl. Cancer Inst. 2015 Mar 1; 107 (3).

BackgroundPhase I trials often include a dose expansion cohort (DEC), in which additional patients are treated at the estimated maximum tolerated dose (MTD) after dose escalation, with the goal of ensuring that data are available from more than six patients at a single dose level. However, protocols do not always detail how, or even if, the additional toxicity data will be used to reanalyze the MTD or whether observed toxicity in the DEC will warrant changing the assigned dose. A DEC strategy has not been statistically justified.MethodsWe conducted a simulation study of two phase I designs: the "3+3" and the Continual Reassessment Method (CRM). We quantified how many patients are assigned the true MTD using a 10 to 20 patient DEC and how a sensible reanalysis using the DEC changes the probability of selecting the true MTD. We compared these results with those from an equivalently sized larger CRM that does not include a DEC.ResultsWith either the 3+3 or CRM, reanalysis with the DEC increased the probability of identifying the true MTD. However, a large CRM without a DEC was more likely to identify the true MTD while still treating 10 or 15 patients at this dose level.ConclusionsWhere feasible, a CRM design with no explicit DEC is preferred to designs that fix a dose for all patients in a DEC.© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

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