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Preclinical optimization of MDM2 antagonist scheduling for cancer treatment by using a model-based approach.

Authors
  • Higgins, Brian
  • Glenn, Kelli
  • Walz, Antje
  • Tovar, Christian
  • Filipovic, Zoran
  • Hussain, Sazzad
  • Lee, Edmund
  • Kolinsky, Kenneth
  • Tannu, Shahid
  • Adames, Violeta
  • Garrido, Rosario
  • Linn, Michael
  • Meille, Christophe
  • Heimbrook, David
  • Vassilev, Lyubomir
  • Packman, Kathryn
Type
Published Article
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
Publication Date
Jul 15, 2014
Volume
20
Issue
14
Pages
3742–3752
Identifiers
DOI: 10.1158/1078-0432.CCR-14-0460
PMID: 24812409
Source
Medline
License
Unknown

Abstract

Besides chronic administration, antitumor activity can be achieved with intermittent schedules of RG7388, as predicted through modeling and simulation. These alternative regimens may potentially ameliorate tolerability issues seen with chronic administration of RG7112, while providing clinical benefit. Thus, both weekly (qw) and daily for five days (5 d on/23 off, qd) schedules were selected for RG7388 clinical testing.

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