Dose Escalation Methods in Phase I Cancer Clinical Trials

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ID: 303390
2009
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Ranked #50 of 333 articles by views in JNCI Journal of the National Cancer Institute

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Abstract
Phase I clinical trials are an essential step in the development of anticancer drugs. The main goal of these studies is to establish the recommended dose and/or schedule of new drugs or drug combinations for phase II trials. The guiding principle for dose escalation in phase I trials is to avoid exposing too many patients to subtherapeutic doses while preserving safety and maintaining rapid accrual. Here we review dose escalation methods for phase I trials, including the rule-based and model-based dose escalation methods that have been developed to evaluate new anticancer agents. Toxicity has traditionally been the primary endpoint for phase I trials involving cytotoxic agents. However, with the emergence of molecularly targeted anticancer agents, potential alternative endpoints to delineate optimal biological activity, such as plasma drug concentration and target inhibition in tumor or surrogate tissues, have been proposed along with new trial designs. We also describe specific methods for drug combinations as well as methods that use a time-to-event endpoint or both toxicity and efficacy as endpoints. Finally, we present the advantages and drawbacks of the various dose escalation methods and discuss specific applications of the methods in developmental oncotherapeutics.
Reference Key
openalex_W2115499099 Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Christophe Le Tourneau, J. Jack Lee, Lillian L. Siu
Journal JNCI Journal of the National Cancer Institute
Year 2009
DOI
10.1093/jnci/djp079
URL
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