Phase I study of MGCD0103 given as a three-times-per-week oral dose in patients with advanced solid tumors.

Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Lillian L SiuMichael A Carducci

Abstract

MGCD0103 is a novel isotype-selective inhibitor of human histone deaceylases (HDACs) with the potential to regulate aberrant gene expression and restore normal growth control in malignancies. A phase I trial of MGCD0103, given as a three-times-per-week oral dose for 2 of every 3 weeks, was performed in patients with advanced solid tumors. Primary end points were safety, tolerability, pharmacokinetics (PK), pharmacodynamic (PD) assessments of HDAC activity, and histone acetylation status in peripheral WBCs. Six dose levels ranging from 12.5 to 56 mg/m(2)/d were evaluated in 38 patients over 99 cycles (median, 2; range, 1 to 11). The recommended phase II dose was 45 mg/m(2)/d. Dose-limiting toxicities consisting of fatigue, nausea, vomiting, anorexia, and dehydration were observed in three (27%) of 11 and two (67%) of three patients treated at the 45 and 56 mg/m(2)/d dose levels, respectively. Disease stabilization for four or more cycles was observed in five (16%) of 32 patients assessable for efficacy. PK analyses demonstrated interpatient variability which was improved by coadministration with low pH beverages. Elimination half-life ranged from 6.7 to 12.2 hours, and no accumulation was observed with repeated dosing. PD evalua...Continue Reading

References

Jul 17, 1998·Current Opinion in Chemical Biology·C A Hassig, S L Schreiber
Mar 11, 1999·Current Opinion in Genetics & Development·T Kouzarides
Nov 21, 2002·Journal of Experimental Therapeutics & Oncology·John L MarshallMichael J Hawkins
Oct 3, 2003·Biochemical and Biophysical Research Communications·Keith B GlaserSteven K Davidsen
May 18, 2004·Cancer Cell·Ping ZhuMartin Göttlicher
Apr 27, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Qin C RyanEdward A Sausville
May 18, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·William Kevin KellyVictoria M Richon
Aug 10, 2005·Journal of Cellular Biochemistry·Milos Dokmanovic, Paul A Marks
Jul 11, 2006·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Mostafa Atri
Aug 11, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Francis GilesKapil Bhalla
Dec 21, 2006·Brain, Behavior, and Immunity·Christian SchubertJoel E Dimsdale
Apr 28, 2007·The Cancer Journal·Janice M Mehnert, Wm Kevin Kelly
May 15, 2007·Biochemical Pharmacology·Keith B Glaser
Jun 20, 2007·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Elise A OlsenMadeleine Duvic
Jul 13, 2007·CA: a Cancer Journal for Clinicians·Drew A TorigianAbass Alavi

❮ Previous
Next ❯

Citations

Aug 1, 2009·Clinical Reviews in Allergy & Immunology·Moshe Szyf
Sep 9, 2011·Molecular Pharmaceutics·Robert W RobeySusan E Bates
Oct 15, 2010·Nature Biotechnology·Theresa K KellyPeter A Jones
Mar 10, 2011·Annals of Oncology : Official Journal of the European Society for Medical Oncology·W P YongJ Zhu
Oct 15, 2008·Annual Review of Pharmacology and Toxicology·Moshe Szyf
Aug 25, 2009·American Journal of Physiology. Lung Cellular and Molecular Physiology·Weichao GuoJoseph A Lasky
Jun 4, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Claire BonfilsZuomei Li
Aug 14, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Luke A WittenburgDouglas H Thamm
Feb 26, 2010·Journal of Inflammation·Hannu KankaanrantaXianzhi Zhang
Jun 3, 2009·Journal of Hematology & Oncology·Shundong CangDelong Liu
Feb 6, 2010·Journal of Hematology & Oncology·Jiahuai TanDelong Liu
Mar 6, 2013·Biologics : Targets & Therapy·Katherine VerverisPaul V Licciardi
Jun 1, 2011·Cancer Management and Research·Nadine Martinet, Philippe Bertrand
Mar 14, 2013·World Journal of Gastroenterology : WJG·Ioannis KoutsounasStamatios Theocharis
Mar 16, 2012·Future Medicinal Chemistry·Berkley E GryderAdegboyega K Oyelere
Aug 26, 2010·Pharmaceuticals·Srividya SubramanianRichard L Piekarz
May 11, 2011·Expert Opinion on Investigational Drugs·Yanis BoumberGuillermo Garcia-Manero
Aug 7, 2010·Expert Opinion on Investigational Drugs·Paul A Marks
Jul 19, 2013·Expert Opinion on Biological Therapy·Frank P Vendetti, Charles M Rudin
Sep 29, 2009·Expert Opinion on Investigational Drugs·Ina OehmeOlaf Witt
Jul 12, 2008·Expert Opinion on Investigational Drugs·Christophe Le Tourneau, Lillian L Siu
Jan 5, 2013·Expert Opinion on Drug Metabolism & Toxicology·Joanna FraczekVera Rogiers
Oct 1, 2011·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Francesco CreaEnrico Mini
Nov 27, 2010·Journal of Molecular and Cellular Cardiology·Timothy A McKinsey
Mar 12, 2010·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Ciro MercurioPier Giuseppe Pelicci
Apr 7, 2009·Cancer Letters·Nicolas BattyJean Pierre J Issa
Feb 14, 2009·International Journal of Radiation Oncology, Biology, Physics·Harlinde De SchutterSandra Nuyts
Sep 12, 2015·Medicinal Research Reviews·Zhiyan XiaoKuo-Hsiung Lee
Dec 23, 2015·Clinical Epigenetics·Clara NerviGiovanni Codacci-Pisanelli
Oct 1, 2008·Cancer Letters·Olaf WittIna Oehme
Mar 31, 2009·International Journal of Cancer. Journal International Du Cancer·Christina RestallAnthony E Dear
Nov 28, 2008·International Journal of Cancer. Journal International Du Cancer·Johanne WeberpalsJim Dimitroulakos
Nov 3, 2010·Liver International : Official Journal of the International Association for the Study of the Liver·Jin-Ping LaiLewis R Roberts
Apr 5, 2013·BJU International·Naomi L SharmaAnne E Kiltie
Aug 26, 2015·Drug Development Research·Saira R AliMichael Z Michael
Oct 2, 2015·Investigational New Drugs·Diana MarkozashviliYegor S Vassetzky

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