File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

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

TitleTwo-stage dose finding for cytostatic agents in phase I oncology trials
Authors
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/
Citation
Statistics in Medicine, 2013, v. 32 n. 4, p. 644-660 How to Cite?
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.
Persistent Identifierhttp://hdl.handle.net/10722/172505
ISSN
2014 Impact Factor: 1.825
2014 SCImago Journal Rankings: 2.061
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorYin, Gen_US
dc.contributor.authorZheng, Sen_US
dc.contributor.authorXu, Jen_US
dc.date.accessioned2012-10-30T06:22:50Z-
dc.date.available2012-10-30T06:22:50Z-
dc.date.issued2013en_US
dc.identifier.citationStatistics in Medicine, 2013, v. 32 n. 4, p. 644-660en_US
dc.identifier.issn0277-6715en_US
dc.identifier.urihttp://hdl.handle.net/10722/172505-
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.en_US
dc.languageengen_US
dc.publisherJohn Wiley & Sons Ltd. The Journal's web site is located at http://www.interscience.wiley.com/jpages/0277-6715/en_US
dc.relation.ispartofStatistics in Medicineen_US
dc.subjectAdaptive Designen_US
dc.subjectCensored Dataen_US
dc.subjectDelayed Responseen_US
dc.subjectDose De-Escalationen_US
dc.subjectDose Escalationen_US
dc.subjectEfficacyen_US
dc.subjectKaplan-Meier Estimatoren_US
dc.subjectTime To Eventen_US
dc.subjectToxicityen_US
dc.titleTwo-stage dose finding for cytostatic agents in phase I oncology trialsen_US
dc.typeArticleen_US
dc.identifier.emailYin, G: gyin@hku.hken_US
dc.identifier.authorityYin, G=rp00831en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1002/sim.5546en_US
dc.identifier.pmid22855354-
dc.identifier.scopuseid_2-s2.0-84872822809en_US
dc.identifier.hkuros211040-
dc.identifier.isiWOS:000313980700010-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridYin, G=8725807500en_US
dc.identifier.scopusauthoridZheng, S=55324225500en_US
dc.identifier.scopusauthoridXu, J=55323925200en_US
dc.identifier.citeulike10989271-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats