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Article: Two-stage dose finding for cytostatic agents in phase I oncology trials
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TitleTwo-stage dose finding for cytostatic agents in phase I oncology trials
 
AuthorsYin, G1 3
Zheng, S2
Xu, J1
 
KeywordsAdaptive Design
Censored Data
Delayed Response
Dose De-Escalation
Dose Escalation
Efficacy
Kaplan-Meier Estimator
Time To Event
Toxicity
 
Issue Date2013
 
PublisherJohn Wiley & Sons Ltd. The Journal's web site is located at http://www.interscience.wiley.com/jpages/0277-6715/
 
CitationStatistics in Medicine, 2013, v. 32 n. 4, p. 644-660 [How to Cite?]
DOI: http://dx.doi.org/10.1002/sim.5546
 
AbstractConventional 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.
 
ISSN0277-6715
2013 Impact Factor: 2.037
 
DOIhttp://dx.doi.org/10.1002/sim.5546
 
DC FieldValue
dc.contributor.authorYin, G
 
dc.contributor.authorZheng, S
 
dc.contributor.authorXu, J
 
dc.date.accessioned2012-10-30T06:22:50Z
 
dc.date.available2012-10-30T06:22:50Z
 
dc.date.issued2013
 
dc.description.abstractConventional 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.naturelink_to_subscribed_fulltext
 
dc.identifier.citationStatistics in Medicine, 2013, v. 32 n. 4, p. 644-660 [How to Cite?]
DOI: http://dx.doi.org/10.1002/sim.5546
 
dc.identifier.citeulike10989271
 
dc.identifier.doihttp://dx.doi.org/10.1002/sim.5546
 
dc.identifier.hkuros211040
 
dc.identifier.issn0277-6715
2013 Impact Factor: 2.037
 
dc.identifier.pmid22855354
 
dc.identifier.scopuseid_2-s2.0-84872822809
 
dc.identifier.urihttp://hdl.handle.net/10722/172505
 
dc.languageeng
 
dc.publisherJohn Wiley & Sons Ltd. The Journal's web site is located at http://www.interscience.wiley.com/jpages/0277-6715/
 
dc.publisher.placeUnited Kingdom
 
dc.relation.ispartofStatistics in Medicine
 
dc.subjectAdaptive Design
 
dc.subjectCensored Data
 
dc.subjectDelayed Response
 
dc.subjectDose De-Escalation
 
dc.subjectDose Escalation
 
dc.subjectEfficacy
 
dc.subjectKaplan-Meier Estimator
 
dc.subjectTime To Event
 
dc.subjectToxicity
 
dc.titleTwo-stage dose finding for cytostatic agents in phase I oncology trials
 
dc.typeArticle
 
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<contributor.author>Zheng, S</contributor.author>
<contributor.author>Xu, J</contributor.author>
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Author Affiliations
  1. The University of Hong Kong
  2. Northeast Normal University
  3. University of Texas M. D. Anderson Cancer Center