A Phase II Trial of Panobinostat, a Histone Deacetylase Inhibitor, in the Treatment of Patients with Refractory Metastatic Renal Cell Carcinoma

被引：70

作者：

Hainsworth, John D. ^{[1
,2
]}

Infante, Jeffrey R. ^{[1
,2
]}

Spigel, David R. ^{[1
,2
]}

Arrowsmith, Edward R. ^{[1
,3
]}

Boccia, Ralph V. ^{[1
,4
]}

Burris, Howard A. ^{[1
,2
]}

机构：

[1] Sarah Cannon Res Inst, Nashville, TN 37203 USA

[2] Tennessee Oncol PLLC, Nashville, TN USA

[3] Chattanooga Oncol Hematol Associates, Chattanooga, TN USA

[4] Ctr Canc & Blood Disorders, Bethesda, MD USA

来源：

CANCER INVESTIGATION | 2011年 / 29卷 / 07期

关键词：

Kidney; panobinostat HDAC inhibitors; INTERFERON-ALPHA; HYDROXAMIC ACID; TRICHOSTATIN; SYNERGY;

D O I：

10.3109/07357907.2011.590568

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Purpose: To evaluate the activity of panobinostat in refractory renal carcinoma. Patients and Methods: Patients with advanced clear cell renal carcinoma who had received previous therapy with at least one angiogenesis inhibitor and one mTOR inhibitor were treated with panobinostat 45 mg orally twice a week, and were reevaluated after 8 weeks. Results: Twenty patients were treated with no objective responses. All patients progressed or stopped treatment prior to the 16-week reevaluation. Panobinostat was generally well-tolerated. Conclusion: Panobinostat had no activity in this group of patients with refractory renal carcinoma. Further development of panobinostat in renal carcinoma is not recommended.

引用

页码：451 / 455

页数：5

共 19 条

[1] Synergy of demethylation and histone deacetylase inhibition in the re-expression of genes silenced in cancer [J].

Cameron, EE ;

Bachman, KE ;

Myöhänen, S ;

Herman, JG ;

Baylin, SB .

NATURE GENETICS, 1999, 21 (01) :103-107

[2] Sorafenib in advanced clear-cell renal-cell carcinoma [J].

Escudier, Bernard ;

Eisen, Tim ;

Stadler, Walter M. ;

Szczylik, Cezary ;

Oudard, Stephane ;

Siebels, Michael ;

Negrier, Sylvie ;

Chevreau, Christine ;

Solska, Ewa ;

Desai, Apurva A. ;

Rolland, Frederic ;

Demkow, Tomasz ;

Hutson, Thomas E. ;

Gore, Martin ;

Freeman, Scott ;

Schwartz, Brian ;

Shan, Minghua ;

Simantov, Ronit ;

Bukowski, Ronald M. .

NEW ENGLAND JOURNAL OF MEDICINE, 2007, 356 (02) :125-134

[3] Phase III Trial of Bevacizumab Plus Interferon Alfa-2a in Patients With Metastatic Renal Cell Carcinoma (AVOREN): Final Analysis of Overall Survival [J].

Escudier, Bernard ;

Bellmunt, Joaquim ;

Negrier, Sylvie ;

Bajetta, Emilio ;

Melichar, Bohuslav ;

Bracarda, Sergio ;

Ravaud, Alain ;

Golding, Sophie ;

Jethwa, Sangeeta ;

Sneller, Vesna .

JOURNAL OF CLINICAL ONCOLOGY, 2010, 28 (13) :2144-2150

[4] A phase I study of intravenous LBH589, a novel cinnamic hydroxamic acid analogue histone deacetylase inhibitor, in patients with refractory hematologic malignancies [J].

Giles, Francis ;

Fischer, Thomas ;

Cortes, Jorge ;

Garcia-Manero, Guillermo ;

Beck, Joachim ;

Ravandi, Farhad ;

Masson, Eric ;

Rae, Patricia ;

Laird, Glen ;

Sharma, Sunil ;

Kantarjian, Hagop ;

Dugan, Margaret ;

Albitar, Maher ;

Bhalla, Kapil .

CLINICAL CANCER RESEARCH, 2006, 12 (15) :4628-4635

[5] Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma [J].

Hudes, Gary ;

Carducci, Michael ;

Tomczak, Piotr ;

Dutcher, Janice ;

Figlin, Robert ;

Kapoor, Anil ;

Staroslawska, Elzbieta ;

Sosman, Jeffrey ;

McDermott, David ;

Bodrogi, Istvan ;

Kovacevic, Zoran ;

Lesovoy, Vladimir ;

Schmidt-Wolf, Ingo G. H. ;

Barbarash, Olga ;

Gokmen, Erhan ;

O'Toole, Timothy ;

Lustgarten, Stephanie ;

Moore, Laurence ;

Motzer, Robert J. .

NEW ENGLAND JOURNAL OF MEDICINE, 2007, 356 (22) :2271-2281

[6] ISOLATION AND STRUCTURAL ELUCIDATION OF NEW CYCLOTETRAPEPTIDES, TRAPOXIN-A AND TRAPOXIN-B, HAVING DETRANSFORMATION ACTIVITIES AS ANTITUMOR AGENTS [J].

ITAZAKI, H ;

NAGASHIMA, K ;

SUGITA, K ;

YOSHIDA, H ;

KAWAMURA, Y ;

YASUDA, Y ;

MATSUMOTO, K ;

ISHII, K ;

UOTANI, N ;

NAKAI, H ;

TERUI, A ;

YOSHIMATSU, S ;

IKENISHI, Y ;

NAKAGAWA, Y .

JOURNAL OF ANTIBIOTICS, 1990, 43 (12) :1524-1532

[7] Decreased acetylation of histone H3 in renal cell carcinoma: A potential target of histone deacetylase inhibitors [J].

Kanao, Kent ;

Mikami, Shuji ;

Mizuno, Ryuichi ;

Shinojima, Toshiaki ;

Murai, Masaru ;

Oya, Mototsugu .

JOURNAL OF UROLOGY, 2008, 180 (03) :1131-1136

[8] NONPARAMETRIC-ESTIMATION FROM INCOMPLETE OBSERVATIONS [J].

KAPLAN, EL ;

MEIER, P .

JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION, 1958, 53 (282) :457-481

[9] Phase I study of an oral histone deacetylase inhibitor, suberoylanilide hydroxamic acid, in patients with advanced cancer [J].

Kelly, WK ;

O'Connor, OA ;

Krug, LM ;

Chiao, JH ;

Heaney, M ;

Curley, T ;

MacGregore-Cortelli, B ;

Tong, W ;

Secrist, JP ;

Schwartz, L ;

Richardson, S ;

Chu, E ;

Olgac, S ;

Marks, PA ;

Scher, H ;

Richon, VM .

JOURNAL OF CLINICAL ONCOLOGY, 2005, 23 (17) :3923-3931

[10]

Kirschbaum M, 2007, J CLIN ONCOL, V25

← 1 2 →