Article: Two-stage dose finding for cytostatic agents in phase I oncology trials

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Title	Two-stage dose finding for cytostatic agents in phase I oncology trials
Authors	Yin, G1 3 Zheng, S2 Xu, J1
Keywords	Adaptive Design Censored Data Delayed Response Dose De-Escalation Dose Escalation Efficacy Kaplan-Meier Estimator Time To Event Toxicity
Issue Date	2013
Publisher	John Wiley & Sons Ltd. The Journal's web site is located at http://www.interscience.wiley.com/jpages/0277-6715/
Citation	Statistics In Medicine, 2013, v. 32 n. 4, p. 644-660 [How to Cite?] DOI: http://dx.doi.org/10.1002/sim.5546
Abstract	Conventional dose-finding methods in oncology are mainly developed for cytotoxic agents with the aim of finding the maximum tolerated dose. In phase I clinical trials with cytostatic agents, such as targeted therapies, designs with toxicity endpoints alone may not work well. For cytostatic agents, the goal is often to find the most efficacious dose that is still tolerable, although these agents are typically less toxic than cytotoxic agents and their efficacy may not monotonically increase with the dose. To effectively differentiate doses for cytostatic agents, we develop a two-stage dose-finding procedure by first identifying the toxicity upper bound of the searching range through dose escalation and then determining the most efficacious dose through dose de-escalation while toxicity is continuously monitored. In oncology, treatment efficacy often takes a relatively long period to exhibit compared with toxicity. To accommodate such delayed response, we model the time to the efficacy event by redistributing the mass of the censored observation to the right and compute the fractional contribution of the censored data. We evaluate the operating characteristics of the new dose-finding design for cytostatic agents and demonstrate its satisfactory performance through simulation studies. © 2012 John Wiley & Sons, Ltd.
ISSN	0277-6715 2011 Impact Factor: 1.877 2011 SCImago Journal Rankings: 0.248
DOI	http://dx.doi.org/10.1002/sim.5546

DC Field	Value
dc.contributor.author	Yin, G
dc.contributor.author	Zheng, S
dc.contributor.author	Xu, J
dc.date.accessioned	2012-10-30T06:22:50Z
dc.date.available	2012-10-30T06:22:50Z
dc.date.issued	2013
dc.description.abstract	Conventional dose-finding methods in oncology are mainly developed for cytotoxic agents with the aim of finding the maximum tolerated dose. In phase I clinical trials with cytostatic agents, such as targeted therapies, designs with toxicity endpoints alone may not work well. For cytostatic agents, the goal is often to find the most efficacious dose that is still tolerable, although these agents are typically less toxic than cytotoxic agents and their efficacy may not monotonically increase with the dose. To effectively differentiate doses for cytostatic agents, we develop a two-stage dose-finding procedure by first identifying the toxicity upper bound of the searching range through dose escalation and then determining the most efficacious dose through dose de-escalation while toxicity is continuously monitored. In oncology, treatment efficacy often takes a relatively long period to exhibit compared with toxicity. To accommodate such delayed response, we model the time to the efficacy event by redistributing the mass of the censored observation to the right and compute the fractional contribution of the censored data. We evaluate the operating characteristics of the new dose-finding design for cytostatic agents and demonstrate its satisfactory performance through simulation studies. © 2012 John Wiley & Sons, Ltd.
dc.description.nature	Link_to_subscribed_fulltext
dc.identifier.citation	Statistics In Medicine, 2013, v. 32 n. 4, p. 644-660 [How to Cite?] DOI: http://dx.doi.org/10.1002/sim.5546
dc.identifier.citeulike	10989271
dc.identifier.doi	http://dx.doi.org/10.1002/sim.5546
dc.identifier.issn	0277-6715 2011 Impact Factor: 1.877 2011 SCImago Journal Rankings: 0.248
dc.identifier.scopus	eid_2-s2.0-84872822809
dc.identifier.uri	http://hdl.handle.net/10722/172505
dc.language	eng
dc.publisher	John Wiley & Sons Ltd. The Journal's web site is located at http://www.interscience.wiley.com/jpages/0277-6715/
dc.publisher.place	United Kingdom
dc.relation.ispartof	Statistics in Medicine
dc.subject	Adaptive Design
dc.subject	Censored Data
dc.subject	Delayed Response
dc.subject	Dose De-Escalation
dc.subject	Dose Escalation
dc.subject	Efficacy
dc.subject	Kaplan-Meier Estimator
dc.subject	Time To Event
dc.subject	Toxicity
dc.title	Two-stage dose finding for cytostatic agents in phase I oncology trials
dc.type	Article

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Author Affiliations

The University of Hong Kong
Northeast Normal University
University of Texas M. D. Anderson Cancer Center

Article: Two-stage dose finding for cytostatic agents in phase I oncology trials

The HKU Scholars Hub has contact details for these author(s).