Skip Navigation



Journal of the National Cancer Institute Advance Access published online on May 12, 2009
JNCI Journal of the National Cancer Institute, doi:10.1093/jnci/djp079
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrowOA All Versions of this Article:
101/10/708    most recent
djp079v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Request Permissions
Google Scholar
Right arrow Articles by Le Tourneau, C.
Right arrow Articles by Siu, L. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Le Tourneau, C.
Right arrow Articles by Siu, L. L.
Related Collections
Right arrowRelated Article in JNCI
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 2009 The Author(s).
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

REVIEW

Dose Escalation Methods in Phase I Cancer Clinical Trials

Christophe Le Tourneau, J. Jack Lee, Lillian L. Siu

Affiliations of authors: Division of Medical Oncology and Hematology, Princess Margaret Hospital, University Health Network, University of Toronto, Toronto, ON, Canada (CLT, LLS); Department of Biostatistics, The University of Texas M. D. Anderson Cancer Center, Houston, TX (JJL)

Correspondence to: Lillian L. Siu, MD, FRCPC, Division of Medical Oncology and Hematology, Princess Margaret Hospital, University Health Network, University of Toronto, 610 University Ave, Ste 5-718, Toronto, ON, Canada M5G 2M9 (e-mail: lillian.siu{at}uhn.on.ca)

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.

Manuscript received October 27, 2008; revised February 17, 2009; accepted March 4, 2009.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?

Related Article in JNCI

IN THIS ISSUE
J Natl Cancer Inst 2009 101: 695. [Extract] [Full Text] [PDF]



This article has been cited by other articles:


Home page
 JNCI J Natl Cancer InstHome page
S. Zohar and J. O'Quigley
Re: Dose Escalation Methods in Phase I Cancer Clinical Trials
J Natl Cancer Inst, November 5, 2009; (2009) djp400v1.
[Full Text] [PDF]

Home page
 JNCI J Natl Cancer InstHome page
C. Le Tourneau, J. J. Lee, and L. L. Siu
Response
J Natl Cancer Inst, November 5, 2009; (2009) djp401v1.
[Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.