Phase II trial of the pan-deacetylase inhibitor panobinostat as a single agent in advanced relapsed/refractory multiple myeloma

Leukemia and Lymphoma

Volumn 53, Issue 9, 2012, Pages 1820-1823

  Wolf, Jeffrey L ^a   Siegel, David ^b   Goldschmidt, Hartmut ^c   Hazell, Katharine ^d   Bourquelot, Priscille M ^d   Bengoudifa, Bourras R ^d   Matous, Jeffrey ^e   Vij, Ravi ^f   De Magalhaes Silverman, Margarida ^g   Abonour, Rafat ^h   Anderson, Kenneth C ⁱ   Lonial, Sagar ^j  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b HACKENSACK UNIVERSITY MEDICAL CENTER   (United States)

^c UNIVERSITY OF HEIDELBERG   (Germany)

^d NOVARTIS PHARMA AG   (Switzerland)

^e Rocky Mountain Blood and Marrow Transplant Program   (United States)

^f WASHINGTON UNIVERSITY   (United States)

^g UNIVERSITY OF IOWA   (United States)

^h INDIANA UNIVERSITY SCHOOL OF MEDICINE   (United States)

ⁱ DANA FARBER CANCER INSTITUTE   (United States)

^j EMORY UNIVERSITY   (United States)

more..

Author keywords

[No Author keywords available]

Indexed keywords

BORTEZOMIB; LENALIDOMIDE; PANOBINOSTAT; THALIDOMIDE;

ADULT; AGED; ANEMIA; ANOREXIA; BACKACHE; BLOOD DISEASE; CANCER SURVIVAL; CONNECTIVE TISSUE DISEASE; CONSTIPATION; CREATININE BLOOD LEVEL; DIARRHEA; DRUG EFFICACY; DYSGEUSIA; DYSPNEA; EYE DISEASE; FATIGUE; FEMALE; FEVER; HEADACHE; HUMAN; HYPERCALCEMIA; HYPOKALEMIA; HYPOMAGNESEMIA; KIDNEY DISEASE; LETTER; LYMPHATIC SYSTEM DISEASE; MALE; MEDIASTINUM DISEASE; MENTAL DISEASE; METABOLIC DISORDER; MULTICENTER STUDY; MULTIPLE MYELOMA; MUSCULOSKELETAL DISEASE; NAUSEA; NEUTROPENIA; NUTRITION DISORDER; PERIPHERAL EDEMA; PHASE 2 CLINICAL TRIAL; PNEUMONIA; PRIORITY JOURNAL; RECURRENT DISEASE; RESPIRATORY TRACT DISEASE; SIDE EFFECT; SINGLE DRUG DOSE; SKIN DISEASE; SOMNOLENCE; THORAX DISEASE; THROMBOCYTOPENIA; TREATMENT OUTCOME; UPPER ABDOMINAL PAIN; UPPER RESPIRATORY TRACT INFECTION; UROGENITAL TRACT DISEASE; VOMITING; WEIGHT REDUCTION;

ADULT; AGED; ANTINEOPLASTIC AGENTS; AREA UNDER CURVE; BORONIC ACIDS; DIARRHEA; DRUG ADMINISTRATION SCHEDULE; DRUG RESISTANCE, NEOPLASM; FEMALE; HISTONE DEACETYLASE INHIBITORS; HUMANS; HYDROXAMIC ACIDS; INDOLES; MALE; METABOLIC CLEARANCE RATE; MIDDLE AGED; MULTIPLE MYELOMA; NAUSEA; NEUTROPENIA; PYRAZINES; RECURRENCE; REMISSION INDUCTION; THALIDOMIDE; THROMBOCYTOPENIA; TREATMENT OUTCOME;

EID: 84862878624     PISSN: 10428194     EISSN: 10292403     Source Type: Journal    
DOI: 10.3109/10428194.2012.661175     Document Type: Letter

References (15)

1. K umar SK, Rajkumar SV, Dispenzieri A, et al. Improved survival in multiple myeloma and the impact of novel therapies. Blood 2008;11: 2516-2520.
2. K umar S, Lee JH, Lahuerta JJ, et al. Risk of progression and survival in multiple myeloma relapsing after therapy with IMiDs and bortezomib: A multicenter international myeloma working group study. Leukemia 2012;26:149-157.
3. A tadja P. Development of the pan-DAC inhibitor panobinostat (LBH589): Successes and challenges. Cancer Lett 2009;280:233-241.
4. B ali P, Pranpat M, Bradner J, et al. Inhibition of histone deacetylase 6 acetylates and disrupts the chaperone function of heat shock protein 90: A novel basis for antileukemia activity of histone deacetylase inhibitors. J Biol Chem 2005;280:26729-26734.
5. C atley L, Weisberg E, Kiziltepe T, et al. Aggresome induction by proteasome inhibitor bortezomib and alpha-tubulin hyperacetylation by tubulin deacetylase (TDAC) inhibitor LBH589 are synergistic in myeloma cells. Blood 2006;108:3441-3449.
6. H ideshima T, Bradner JE, Wong J, et al. Small-molecule inhibition of proteasome and aggresome function induces synergistic antitumor activity in multiple myeloma. Proc Natl Acad Sci USA 2005;102:8567-8572.
7. O cio EM, Vilanova D, Atadja P, et al. In vitro and in vivo rationale for the triple combination of panobinostat (LBH589) and dexamethasone with either bortezomib or lenalidomide in multiple myeloma. Haematologica 2010;95:794-803.
8. E llis L, Pan Y, Smyth GK, et al. Histone deacetylase inhibitor panobinostat induces clinical responses with associated alterations in gene expression profi les in cutaneous T-cell lymphoma. Clin Cancer Res 2008;14:4500-4510. Durie BG
9. Durie BG, Harousseau JL, Miguel JS, et al. International uniform response criteria for multiple myeloma. Leukemia 2006;20:1467-1473.
10. I nternational Myeloma Working Group. Criteria for the classifi cation of monoclonal gammopathies, multiple myeloma and related disorders: A report of the International Myeloma Working Group. Br J Haematol 2003;121:749-757.
11. Bladé J, Samson D, Reece D, et al. Criteria for evaluating disease response and progression in patients with multiple myeloma treated by high-dose therapy and haemopoietic stem cell transplantation. Myeloma Subcommittee of the EBMT. European Group for Blood and Marrow Transplant. Br J Haematol 1998;102:1115-1123.
12. Schmitt S, Ho AD, Goldschmidt H. Th e oral histone deacetylase inhibitor LBH589 is a potential and promising therapeutic agent in multiple myeloma after at least two lines of chemotherapy including bortezomib or lenalidomide. Onkologie 2010;33:183-186.
13. Richardson P, Mitsiades C, Colson K, et al. Phase I trial of oral vorinostat (suberoylanilide hydroxamic acid, SAHA) in patients with advanced multiple myeloma. Leuk Lymphoma 2008;49:502-507.
14. N iesvizky R, Ely S, Mark T, et al. Phase 2 trial of the histone deacetylase inhibitor romidepsin for the treatment of refractory multiple myeloma. Cancer 2011;117:336-342.
15. S an-Miguel JF, Richardson PGG, Sezer O, et al. A phase lb study of oral panobinostat and IV bortezomib in relapsed or relapsed and refractory multiple myeloma. J Clin Oncol 2011;29(Suppl.): Abstract 8075.