A phase 1 study of efatutazone, an oral peroxisome proliferator-activated receptor gamma agonist, administered to patients with advanced malignancies.

Cancer
Michael J PishvaianGeorge D Demetri

Abstract

Efatutazone (CS-7017), a novel peroxisome proliferator-activated receptor gamma (PPARγ) agonist, exerts anticancer activity in preclinical models. The authors conducted a phase 1 study to determine the recommended phase 2 dose, safety, tolerability, and pharmacokinetics of efatutazone. Patients with advanced solid malignancies and no curative therapeutic options were enrolled to receive a given dose of efatutazone, administered orally (PO) twice daily for 6 weeks, in a 3 + 3 intercohort dose-escalation trial. After the third patient, patients with diabetes mellitus were excluded. Efatutazone dosing continued until disease progression or unacceptable toxicity, with measurement of efatutazone pharmacokinetics and plasma adiponectin levels. Thirty-one patients received efatutazone at doses ranging from 0.10 to 1.15 mg PO twice daily. Dose escalation stopped when maximal impact on PPARγ-related biomarkers had been reached before any protocol-defined maximum-tolerated dose level. On the basis of a population pharmacokinetic/pharmacodynamic analysis, the recommended phase 2 dose was 0.5 mg PO twice daily. A majority of patients experienced peripheral edema (53.3%), often requiring diuretics. Three episodes of dose-limiting toxicities...Continue Reading

References

Jan 7, 1997·Proceedings of the National Academy of Sciences of the United States of America·P TontonozB M Spiegelman
Mar 31, 1999·Proceedings of the National Academy of Sciences of the United States of America·G D DemetriS Singer
Jun 6, 2000·Nature·S KerstenW Wahli
Sep 14, 2000·Proceedings of the National Academy of Sciences of the United States of America·E MuellerP W Kantoff
Nov 23, 2000·Proceedings of the National Academy of Sciences of the United States of America·R A GuptaR N DuBois
Jul 19, 2001·The Journal of Biological Chemistry·E D Rosen, B M Spiegelman
Jan 31, 2002·Annual Review of Medicine·Joel Berger, David E Moller
Jun 25, 2002·The Journal of Laboratory and Clinical Medicine·Mohammad Azharul Karim RumiYoshikazu Kinoshita
Apr 20, 2007·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Rangaswamy GovindarajanNicholas P Lang
May 31, 2008·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Naomi ShimazakiShinichi Kurakata
Jul 4, 2008·PPAR Research·Elke Burgermeister, Rony Seger
Sep 26, 2009·Biochimica Et Biophysica Acta·S Fogarty, D G Hardie

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Citations

Apr 30, 2013·Current Diabetes Reports·Hanford YauKenneth Cusi
Mar 20, 2014·Nature Reviews. Clinical Oncology·Mark LinchCharlotte Benson
Mar 7, 2014·Expert Opinion on Investigational Drugs·Hardik JoshiC S Ramaa
Dec 10, 2015·Advances in Anatomic Pathology·Khin ThwayCyril Fisher
Nov 7, 2015·European Journal of Pharmacology·Amreen MughalAjit Vikram
Nov 25, 2014·Expert Opinion on Therapeutic Patents·Ichiro Takada, Makoto Makishima
Apr 14, 2015·BioMed Research International·Eleonore Fröhlich, Richard Wahl
Feb 26, 2015·Frontiers in Surgery·Lucas E MatthyssensWim P Ceelen
May 20, 2016·International Journal of Cancer. Journal International Du Cancer·Vignesh Ramesh, Kumaresan Ganesan
Feb 1, 2017·Expert Review of Clinical Pharmacology·Maristella SaponaraAlessandro Gronchi
Mar 11, 2016·Journal of Oncology Practice·Eytan Ben Ami, Suzanne George
Jan 20, 2018·Breast Cancer Research and Treatment·Virginie OryAnna T Riegel
Oct 27, 2018·Current Treatment Options in Oncology·Sarah Abaricia, Angela C Hirbe
Nov 18, 2018·Endocrine-related Cancer·Priscilla A Furth
Jun 20, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Raymond L KongerRavi P Sahu
Apr 17, 2013·The Journal of Clinical Endocrinology and Metabolism·R C SmallridgeR Von Roemeling
Dec 9, 2017·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Alex Thomas John LeeRobin Lewis Jones
Apr 6, 2018·International Journal of Oncology·Christelle ColinSandra Kuntz
Sep 19, 2014·Diabetes & Vascular Disease Research : Official Journal of the International Society of Diabetes and Vascular Disease·Stefan Z LutzHans-Ulrich Häring
Aug 14, 2020·International Journal of Molecular Sciences·Nicole Wagner, Kay-Dietrich Wagner
Mar 10, 2017·Frontiers in Endocrinology·Veronica VellaRoberta Malaguarnera
Sep 18, 2020·Cancers·Giuseppina AugimeriDaniela Bonofiglio
May 29, 2019·Expert Opinion on Pharmacotherapy·Lorena P Suarez-KellyAlessandro Gronchi
May 10, 2019·Cancer Science·Yu Jin KimYoon-La Choi
Dec 17, 2014·Cancer Prevention Research·Ariane F Busso-LopesSilvia R Rogatto
Sep 5, 2019·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Roberta FrapolliMaurizio D'Incalci
Nov 26, 2013·Cancer Research·Hiroshi SawayamaHideo Baba
Jan 28, 2021·International Journal of Molecular Sciences·Emi MashimaMotonobu Nakamura
Jul 2, 2021·Frontiers in Oncology·Zeyaul IslamPrasanna R Kolatkar

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