Combination epigenetic therapy has efficacy in patients with refractory advanced non-small cell lung cancer.

Cancer Discovery
Rosalyn A JuergensCharles M Rudin

Abstract

Epigenetic alterations are strongly associated with the development of cancer. We conducted a phase I/II trial of combined epigenetic therapy with azacitidine and entinostat, inhibitors of DNA methylation and histone deacetylation, respectively, in extensively pretreated patients with recurrent metastatic non-small cell lung cancer. This therapy is well tolerated, and objective responses were observed, including a complete response and a partial response in a patient who remains alive and without disease progression approximately 2 years after completing protocol therapy. Median survival in the entire cohort was 6.4 months (95% CI 3.8-9.2), comparing favorably with existing therapeutic options. Demethylation of a set of 4 epigenetically silenced genes known to be associated with lung cancer was detectable in serial blood samples in these patients and was associated with improved progression-free (P = 0.034) and overall survival (P = 0.035). Four of 19 patients had major objective responses to subsequent anticancer therapies given immediately after epigenetic therapy. This study demonstrates that combined epigenetic therapy with low-dose azacitidine and entinostat results in objective, durable responses in patients with solid tu...Continue Reading

References

Sep 3, 1996·Proceedings of the National Academy of Sciences of the United States of America·J G HermanS B Baylin
Dec 18, 2001·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·R L Momparler, J Ayoub
Feb 5, 2002·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Manfred Kollroser, Caroline Schober
May 16, 2002·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Lewis R SilvermanJames F Holland
Mar 6, 2003·Journal of the National Cancer Institute·Jonathan C ChengEric U Selker
Aug 2, 2003·Cancer Cell·Ricky W Johnstone, Jonathan D Licht
Aug 7, 2003·Seminars in Radiation Oncology·Andy TrottiPhilip Rubin
Sep 17, 2003·The Journal of Pharmacology and Experimental Therapeutics·Erding HuMichael Jaye
Sep 26, 2003·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Gabriella SozziUgo Pastorino
Nov 25, 2003·The New England Journal of Medicine·James G Herman, Stephen B Baylin
Mar 31, 2004·The Journal of Thoracic and Cardiovascular Surgery·Malcolm V BrockStephen C Yang
Nov 24, 2004·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Ming ZhaoSharyn D Baker
Apr 27, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Michelle A RudekSharyn D Baker
Sep 7, 2006·Nature Reviews. Drug Discovery·Jessica E BoldenRicky W Johnstone
Sep 15, 2006·Journal of Pharmaceutical and Biomedical Analysis·Ming ZhaoSharyn D Baker
Feb 27, 2007·Cell·Peter A Jones, Stephen B Baylin
Jan 4, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·David S SchrumpSeth M Steinberg
Mar 14, 2008·The New England Journal of Medicine·Malcolm V BrockJames G Herman
Apr 22, 2008·Investigational New Drugs·Johan VansteenkistePatrick Schöffski
Jun 4, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Alex R ShoemakerSteven W Elmore
Oct 18, 2008·Cancer Control : Journal of the Moffitt Cancer Center·Alan F List
Oct 3, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Fadi BraitehRazelle Kurzrock
Oct 25, 2008·Molecular Cancer·Paul P AnglimIte A Laird-Offringa
Oct 1, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jianqing LinMichael A Carducci
Dec 21, 2010·Cancer Research·Harsh Vardhan Jain, Michael Meyer-Hermann
Jan 22, 2011·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Rafael SireraCarlos Camps
Feb 2, 2011·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Leena GandhiCharles M Rudin
Feb 9, 2011·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Charles M RudinGary Gordon
Mar 23, 2011·Expert Review of Anticancer Therapy·Rebecca A Howman, H Miles Prince
Apr 13, 2011·Genes, Chromosomes & Cancer·Laia Simó-RiudalbasManel Esteller
May 18, 2011·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Guillermo Garcia-ManeroBarry Skikne
Jun 10, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Young Joo LeeJin Soo Lee

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Citations

Sep 9, 2011·Cancer Chemotherapy and Pharmacology·Julie BaumanDennie Jones
Sep 17, 2013·Cancer Chemotherapy and Pharmacology·Vasiliki PettaKonstantinos Syrigos
Jul 28, 2012·Journal of Mammary Gland Biology and Neoplasia·Roisin Connolly, Vered Stearns
May 29, 2012·Cancer Letters·Somaira NowsheenAlexandros G Georgakilas
Dec 18, 2013·Journal of Medicinal Chemistry·Saâdia AsgatayDominique Guianvarc'h
Jun 7, 2013·Journal of Human Genetics·Kiyoshi AsadaToshikazu Ushijima
Jan 12, 2013·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Shuji OginoEdward Giovannucci
Apr 3, 2013·Nature Reviews. Clinical Oncology·Nilofer AzadStephen B Baylin
Dec 7, 2013·Journal of the National Cancer Institute·David J Stewart
Feb 15, 2013·Nucleic Acids Research·Kurinji PandiyanGangning Liang
May 17, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Elizabeth R Lawlor, Carol J Thiele
Mar 1, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Hariharan Easwaran, Stephen B Baylin
Feb 19, 2013·American Journal of Respiratory and Critical Care Medicine·Ivan O Rosas, Ivana V Yang
Dec 28, 2012·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Kei SuzukiPrasad S Adusumilli
May 3, 2012·Proceedings of the American Thoracic Society·Stephen B Baylin
Feb 28, 2013·International Journal of Molecular Sciences·Paolo RomaniaRossella Rota
Jul 23, 2013·International Journal of Molecular Sciences·Yannick DelpuJérôme Torrisani
Oct 25, 2013·International Journal of Molecular Sciences·Sibaji SarkarMcKenna Longacre
Aug 28, 2012·Epigenomics·Sierk Haenisch, Ingolf Cascorbi
Mar 28, 2013·Journal of Drug Delivery·Eleftheria Hatzimichael, Tim Crook
Nov 29, 2013·Epigenomics·Susanne M HenningDavid Heber
Nov 26, 2013·Journal of the National Cancer Institute·Catia MoutinhoManel Esteller
May 9, 2014·Epigenomics·Shannon Byler, Sibaji Sarkar
Jul 30, 2014·Proceedings of the National Academy of Sciences of the United States of America·KiBem KimShibin Zhou
Sep 10, 2014·Biochemical and Biophysical Research Communications·Naoko Hattori, Toshikazu Ushijima
Jul 13, 2014·Biochemical and Biophysical Research Communications·Dashyant Dhanak, Paul Jackson
Aug 28, 2014·Future Medicinal Chemistry·Dominique Guianvarc'h, Paola Barbara Arimondo
Oct 2, 2012·Archives of Pathology & Laboratory Medicine·Laura E MacConaill
Feb 11, 2014·Gastric Cancer : Official Journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association·Yukie YodaToshikazu Ushijima
Oct 5, 2012·Expert Opinion on Therapeutic Patents·Jacques FahyPaola B Arimondo
Jul 16, 2014·Expert Review of Anticancer Therapy·Seth A Brodie, Johann C Brandes
Aug 20, 2014·Expert Review of Molecular Diagnostics·Angela A GuzzettaNita Ahuja
Jul 19, 2013·Expert Opinion on Biological Therapy·Frank P Vendetti, Charles M Rudin
May 26, 2015·Expert Opinion on Investigational Drugs·Richard L Momparler, Sylvie Côté
Jun 23, 2015·Expert Opinion on Investigational Drugs·Rossana RuizChristian Rolfo
Feb 11, 2016·Seminars in Immunology·Lidia RobertSiwen Hu-Lieskovan
Nov 28, 2012·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Samir Witta
Dec 24, 2014·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Daniel MorgenszternRamaswamy Govindan
Apr 29, 2014·Pharmacology & Therapeutics·Prithviraj BoseSteven Grant
Jan 16, 2016·Annual Review of Medicine·Nita AhujaStephen B Baylin

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