A phase II study of the histone deacetylase inhibitor vorinostat combined with tamoxifen for the treatment of patients with hormone therapy-resistant breast cancer
Pamela N. Munster,K. T. Thurn,Scott Thomas,Paromita Raha,Mira Lacevic,Ashleigh Miller,Michelle E. Melisko,Roohi Ismail-Khan,Hope S. Rugo,Mark M. Moasser,Susan Minton +10 more
TLDR
Correlative studies suggest that HDAC2 expression is a predictive marker and histone hyperacetylation is a useful pharmacodynamic marker for the efficacy of this combination of vorinostat and tamoxifen, and exhibits encouraging activity in reversing hormone resistance.Abstract:
Histone deacetylases (HDACs) are crucial components of the oestrogen receptor (ER) transcriptional complex. Preclinically, HDAC inhibitors can reverse tamoxifen/aromatase inhibitor resistance in hormone receptor-positive breast cancer. This concept was examined in a phase II combination trial with correlative end points. Patients with ER-positive metastatic breast cancer progressing on endocrine therapy were treated with 400 mg of vorinostat daily for 3 of 4 weeks and 20 mg tamoxifen daily, continuously. Histone acetylation and HDAC2 expression in peripheral blood mononuclear cells were also evaluated. In all, 43 patients (median age 56 years (31–71)) were treated, 25 (58%) received prior adjuvant tamoxifen, 29 (67%) failed one prior chemotherapy regimen, 42 (98%) progressed after one, and 23 (54%) after two aromatase inhibitors. The objective response rate by Response Evaluation Criteria in Solid Tumours criteria was 19% and the clinical benefit rate (response or stable disease >24 weeks) was 40%. The median response duration was 10.3 months (confidence interval: 8.1–12.4). Histone hyperacetylation and higher baseline HDAC2 levels correlated with response. The combination of vorinostat and tamoxifen is well tolerated and exhibits encouraging activity in reversing hormone resistance. Correlative studies suggest that HDAC2 expression is a predictive marker and histone hyperacetylation is a useful pharmacodynamic marker for the efficacy of this combination.read more
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Histone deacetylases and their inhibitors in cancer, neurological diseases and immune disorders
TL;DR: The development of small-molecule HDAC inhibitors and their use in the laboratory, in preclinical models and in the clinic are highlighted.
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Histone Deacetylase Inhibitors as Anticancer Drugs.
TL;DR: Different classes of HDAC inhibitors, mechanisms of their actions and novel results of preclinical and clinical studies are summarized, including the combination with other therapeutic modalities are discussed.
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HDACs and HDAC Inhibitors in Cancer Development and Therapy
Yixuan Li,Edward Seto +1 more
TL;DR: The role of HDACs in cancer and the therapeutic potential ofHDAC inhibitors (HDACi) as emerging drugs in cancer treatment are discussed.
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Combination Therapy With Histone Deacetylase Inhibitors (HDACi) for the Treatment of Cancer: Achieving the Full Therapeutic Potential of HDACi
TL;DR: The research thus far on HDACi in combination therapy, with other anticancer agents and their translation into preclinical and clinical studies is summarized and potential biomarkers to either select or predict a patient’s response to these agents are discussed, in order to limit the off-target toxicity associated withHDACi.
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HDAC inhibitors in cancer biology: emerging mechanisms and clinical applications
Omar Khan,Nicholas B. La Thangue +1 more
TL;DR: Developments in the understanding of molecular events that underlie the anti‐cancer effects of HDAC inhibitors are discussed and this information is related to the emerging clinical picture for the application of these inhibitors in the treatment of cancer.
References
More filters
Journal ArticleDOI
New Guidelines to Evaluate the Response to Treatment in Solid Tumors
Patrick Therasse,Susan G. Arbuck,Elizabeth Eisenhauer,Jantien Wanders,Richard Kaplan,Larry Rubinstein,Jaap Verweij,Martine Van Glabbeke,Allan T. van Oosterom,Michaele C. Christian,S. Gwyther +10 more
TL;DR: A model by which a combined assessment of all existing lesions, characterized by target lesions and nontarget lesions, is used to extrapolate an overall response to treatment is proposed, which is largely validated by the Response Evaluation Criteria in Solid Tumors Group and integrated into the present guidelines.
Journal ArticleDOI
Cancer statistics, 2010
TL;DR: The American Cancer Society as mentioned in this paper estimated the number of new cancer cases and deaths expected in the United States in the current year and compiles the most recent data regarding cancer incidence, mortality, and survival based on incidence data from the National Cancer Institute, the Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries and mortality data from National Center for Health Statistics.
Journal ArticleDOI
Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials
O. Abe,R. Abe,K. Enomoto,K. Kikuchi,H. Koyama,H. Masuda,Y. Nomura,K. Sakai,K. Sugimachi,T. Tominaga,J. Uchino,M. Yoshida,J. L. Haybittle,C Davies,V. J. Harvey,T. M. Holdaway,R. G. Kay,B. H. Mason,John F. Forbes,Nicholas Wilcken,M. Gnant,Raimund Jakesz,M. Ploner,H. M. A. Yosef,C. Focan,J. P. Lobelle,U. Peek,G. D. Oates,Janet T. Powell,M. Durand,L. Mauriac,A. Di Leo,Stella Dolci,M.J. Piccart,M. B. Masood,D. Parker,J. J. Price,Pierre Hupperets,Sue Jackson,Joseph Ragaz,Donna L. Berry,Gloria Broadwater,C. Cirrincione,Hyman B. Muss,Larry Norton,Raymond B. Weiss,H. Abu-Zahra,S. M. Portnoj,Michael J. Baum,Jack Cuzick,Joan Houghton,David Riley,N. H. Gordon,H. L. Davis,A. Beatrice,J. Mihura,A. Naja,Y. Lehingue,P. Romestaing,J. B. Dubois,Thierry Delozier,J. Mace-Lesec'h,P. Rambert,O. Andrysek,J. Barkmanova,Julie Owen,P. Meier,A Howell,G. C. Ribeiro,R. Swindell,R Alison,J Boreham,Matthew Clarke,Rory Collins,Sarah C. Darby,P. Elphinstone,Vaughan Evans,Jon Godwin,Richard Gray,C. S. Harwood,C. Hicks,Spencer L. James,Elizabeth MacKinnon,Paul McGale,Theresa McHugh,Graham M. Mead,Richard Peto,Yisong Wang,J. Albano,C. F. de Oliveira,H. Gervasio,J. Gordilho,H Johansen,Henning T. Mouridsen,Rebecca Gelman,J.R. Harris,I. C. Henderson,Charles L. Shapiro,K. W. Andersen,C. K. Axelsson,M. Blichert-Toft,S. Moller,Jens Overgaard,Marie Overgaard,Carsten Rose,B. Cartensen,T. Palshof,H. J. Trampisch,Otilia Dalesio,E.G.E. de Vries,Sjoerd Rodenhuis,H. van Tinteren,R. L. Comis,Nancy E. Davidson,Nicholas J. Robert,George W. Sledge,Douglass C. Tormey,William C. Wood,David Cameron,Udi Chetty,P. Forrest,W. Jack,J. Rossbach,Jan G. M. Klijn,A. D. Treurniet-Donker,W. L. J. van Putten,Alberto Costa,Umberto Veronesi,H. Bartelink,L. Duchateau,C. Legrand,RJ Sylvester,J.A. van der Hage,C.J.H. van de Velde,M. P. Cunningham,R. Catalano,R. H. Creech,Jacques Bonneterre,P. Fargeot,Pierre Fumoleau,Pierre Kerbrat,Moïse Namer,Walter Jonat,Manfred Kaufmann,Martin Schumacher,G. von Minckwitz,G. Bastert,H. Rauschecker,R. Sauer,Willi Sauerbrei,A.J. Schauer,A. de Schryver,L. Vakaet,M. Belfiglio,A. Nicolucci,F. Pellegrini,M. Sacco,M. Valentini,C. S. McArdle,D. C. Smith,E. Galligioni,Francesco Boccardo,AU Rubagotti,D. M. Dent,C. A. Gudgeon,A. Hacking,A. Erazo,J. Y. Medina,M. Izuo,Y. Morishita,H. Takei,I.S. Fentiman,John L. Hayward,R D Rubens,D. Skilton,H. Graeff,Fritz Jänicke,C. Meisner,H. R. Scheurlen,D. von Fournier,Urania Dafni,G. Fountzilas,P. Klefstrom,Carl Blomqvist,T. Saarto,R. Margreiter,Bernard Asselain,R. J. Salmon,J. R. Vilcoq,Rodrigo Arriagada,Christopher Hill,A. Laplanche,M. G. Le,M. Spielmann,Paolo Bruzzi,E. Montanaro,R. Rosso,M. R. Sertoli,M. Venturini,Dino Amadori,J. Benraadt,M. Kooi,A. O. van de Velde,J. A. van Dongen,J. B. Vermorken,Monica Castiglione,F. Cavalli,A. S. Coates,J. Collins,JF Forbes,Richard D. Gelber,A. Goldhirsch,J. Lindtner,Karen N. Price,C. M. Rudenstam,H.-J. Senn,Judith M Bliss,Clair Chilvers,R. C. Coombes,Emma Hall,Michel Marty,R. V. Borovik,G. Brufman,H. Hayat,E. Robinson,N. Wigler,Gianni Bonadonna,T. Camerini,G. De Palo,M. Del Vecchio,F. Formelli,Pinuccia Valagussa,A Martoni,F. Pannuti,G. Cocconi,A. Colozza,R. Camisa,K. Aogi,S. Takashima,T. Ikeda,K. Inokuchi,K. Sawa,H. Sonoo,S. Korzeniowski,J. Skolyszewski,M. Ogawa,J. Yamashita,J. Bonte,R. Christiaens,Robert Paridaens,W. Van den Boegart,P. Martin,S. Romain,T. Hakes,Clifford A. Hudis,R. Wittes,G. Giokas,D. Kondylis,B. Lissaios,R. de la Huerta,M. G. Sainz,R. Altemus,K. Cowan,David N. Danforth,Allen S. Lichter,Marc E. Lippman,Joyce A. O'Shaughnessy,Lori J. Pierce,Seth M. Steinberg,D. Venzon,JoAnne Zujewski,A. Paradiso,M. De Lena,F. Schittulli,J. Myles,J. L. Pater,Kathleen I. Pritchard,Stewart J. Anderson,G. Bass,Anna Brown,John Bryant,J. Costantino,James J. Dignam,Bernard Fisher,C Redmond,Sam Wieand,Norman Wolmark,I. M. Jackson,Mike K. Palmer,JN Ingle,Vera J. Suman,Nils-Olof Bengtsson,H. Jonsson,Lars-Gunnar Larsson,J. P. Lythgoe,M. Kissin,Bjørn Erikstein,E Hannisdal,A. B. Jacobsen,J. E. Varhaug,S. Gundersen,Martin Hauer-Jensen,H. Host,R. Nissen-Meyer,Roger W. Blamey,A. Mitchell,Morgan Da,J.F.R. Robertson,M. Di Palma,G. Mathe,J. L. Misset,R. M. Clark,Mitch Levine,K Morimoto,Y. Takatsuka,E. Crossley,Al Harris,Denis Talbot,Mark Taylor,B. di Blasio,V. Ivanov,Vladimir Semiglazov,J. Brockschmidt,M. R. Cooper,H. Ueo,Carla I. Falkson,Roger A'Hern,Stanley W. Ashley,T. J. Powles,Ian E. Smith,John Yarnold,J.-C. Gazet,N. Cocoran,N. Deshpande,L. di Martino,P. Douglas,A. Lindtner,G Notter,A. J. S. Bryant,G. H. Ewing,L. A. Firth,J. L. Krushen-Kosloski,L. Foster,W.D. George,Helen J. Stewart,P. Stroner,Per-Uno Malmström,Torgil Möller,Stefan Rydén,Ingrid Tengrup,Lena Tennvall-Nittby,J. Carstenssen,M. Dufmats,Thomas Hatschek,Bo Nordenskjöld,Martin Söderberg,John T. Carpenter,KS Albain,J. Crowley,Stuart A. Green,Silvana Martino,CK Osborne,Peter M. Ravdin,U. Glas,Ulla Johansson,L E Rutqvist,T. Singnomklao,Arne Wallgren,Rudolf Maibach,Beat Thürlimann,Hermann Brenner,A. Hercbergs,M Yoshimoto,Gerrit DeBoer,Alexander H.G. Paterson,JW Meakin,T. Panzarella,Y. Shan,Y. F. Shao,X. Wang,D. B. Zhao,Z. M. Chen,H. C. Pan,J. Bahi,M. Reid,M. Spittle,G. P. Deutsch,F. Senanayake,D. L. W. Kwong,Angelo Raffaele Bianco,Chiara Carlomagno,M. De Laurentiis,S. De Placido,Aman U. Buzdar,Tae C Smith,Jonas Bergh,Lars Holmberg,Göran Liljegren,Jan Nilsson,M. Seifert,P. Sevelda,C. C. Zielinsky,R. B. Buchanan,M. Cross,G.T. Royle,Janet A. Dunn,Robert Kerrin Hills,Michael Lee,J. M. Morrison,D. Spooner,A. Litton,Rowan T. Chlebowski,H. Caffier +412 more
TL;DR: The 10-year and 15-year effects of various systemic adjuvant therapies on breast cancer recurrence and survival are reported and it is found that the cumulative reduction in mortality is more than twice as big at 15 years as at 5 years after diagnosis.
Journal ArticleDOI
New guidelines to evaluate the response to treatment in solid tumors
Patrick Therasse,Susan G. Arbuck,Elizabeth Eisenhauer,Jantien Wanders,Richard Kaplan,Larry Rubinstein,Jaap Verweij,Martine Van Glabbeke,Allan T. van Oosterom,Michaele C. Christian,S. Gwyther +10 more
TL;DR: In this article, the authors proposed a model by which a combined assessment of all existing lesions, characterized by target lesions (to be measured) and nontarget lesions, is used to extrapolate an overall response to treatment.
Journal ArticleDOI
Phase 2 trial of oral vorinostat (suberoylanilide hydroxamic acid, SAHA) for refractory cutaneous T-cell lymphoma (CTCL)
Madeleine Duvic,Rakhshandra Talpur,Xiao Ni,Chunlei Zhang,Parul Hazarika,Cecilia Kelly,Judy Chiao,John F. Reilly,Justin L. Ricker,Victoria M. Richon,Stanley R. Frankel +10 more
TL;DR: Vorinostat demonstrated activity in heavily pretreated patients with CTCL and the 400 mg daily regimen had the most favorable safety profile and is being further evaluated.
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