Panobinostat in lymphoid and myeloid malignancies

Expert Opinion on Investigational Drugs

Volumn 22, Issue 9, 2013, Pages 1211-1223

  Khot, Amit ^a   Dickinson, Michael ^a   Prince, H Miles ^a  

^a PETER MACCALLUM CANCER CENTRE   (Australia)

Author keywords

HDAC inhibitors; Leukemia; Lymphoma; Panobinostat

Indexed keywords

AZACITIDINE; BELINOSTAT; BEXAROTENE; BORTEZOMIB; CYTARABINE; DEXAMETHASONE; ENTINOSTAT; GEMTUZUMAB OZOGAMICIN; IDARUBICIN; LENALIDOMIDE; MITOXANTRONE; MOCETINOSTAT; PANOBINOSTAT; ROMIDEPSIN; VORINOSTAT;

ACUTE GRANULOCYTIC LEUKEMIA; ANEMIA; ANOREXIA; ARTICLE; B CELL LYMPHOMA; BLEEDING; BONE MARROW SUPPRESSION; CELLULAR DISTRIBUTION; COMBINATION CHEMOTHERAPY; CUTANEOUS T CELL LYMPHOMA; DIARRHEA; DOSE RESPONSE; DRUG ABSORPTION; DRUG ACCUMULATION; DRUG BIOAVAILABILITY; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG HALF LIFE; DRUG METABOLISM; DRUG SAFETY; DRUG STRUCTURE; DRUG TOLERABILITY; DRUG WITHDRAWAL; FATIGUE; HEART ATRIUM FIBRILLATION; HUMAN; IC 50; INFECTION; MANTLE CELL LYMPHOMA; MAXIMUM PLASMA CONCENTRATION; MAXIMUM TOLERATED DOSE; MULTIPLE CYCLE TREATMENT; MYELODYSPLASTIC SYNDROME; MYELOFIBROSIS; MYELOMA; NAUSEA; NEUTROPENIA; NONHODGKIN LYMPHOMA; PERIPHERAL T CELL LYMPHOMA; PHASE 2 CLINICAL TRIAL (TOPIC); QT PROLONGATION; SUBCUTANEOUS T CELL LYMPHOMA; THROMBOCYTOPENIA; TORSADE DES POINTES; TREATMENT RESPONSE; TREATMENT WITHDRAWAL; WALDENSTROEM MACROGLOBULINEMIA;

ADMINISTRATION, ORAL; ANTINEOPLASTIC AGENTS; APOPTOSIS; CELL CYCLE; CLINICAL TRIALS, PHASE II AS TOPIC; DISEASE PROGRESSION; DRUG ADMINISTRATION SCHEDULE; HEMATOLOGIC NEOPLASMS; HISTONE DEACETYLASE INHIBITORS; HUMANS; HYDROXAMIC ACIDS; INDOLES;

EID: 84882261832     PISSN: 13543784     EISSN: 17447658     Source Type: Journal    
DOI: 10.1517/13543784.2013.815165     Document Type: Article

References (64)

1. Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin 2010;60(5):277-300
2. Vaughan WP, Karp JE. The long road to a cure for acute myelocytic leukemia: from intensity to specificity. J Clin Oncol 2008;26(21):3475-7
3. Dores GM, Devesa SS, Curtis RE, et al. Acute leukemia incidence and patient survival among children and adults in the United States, 2001-2007. Blood 2012;119(1):34-43
4. Vose J, Armitage J, Weisenburger D; Project IT-CL. International peripheral T-cell and natural killer/T-Cell lymphoma study: pathology findings and clinical outcomes. J Clin Oncol 2008;26(25):4124-30
5. Sant M, Allemani C, Tereanu C, et al. Incidence of hematologic malignancies in Europe by morphologic subtype: results of the HAEMACARE project. Blood 2010;116(19):3724-34
6. Bazargan A, Tam CS, Keating MJ. Predicting survival in chronic lymphocytic leukemia. Expert Rev Anticancer Ther 2012;12(3):393-403
7. Moreau P, Richardson PG, Cavo M, et al. Proteasome inhibitors in multiple myeloma: 10 years later. Blood 2012;120(5):947-59
8. Neri P, Bahlis NJ, Lonial S. Panobinostat for the treatment of multiple myeloma. Expert Opin Investig Drugs 2012;21(5):733-47
9. Friedberg JW. Relapsed/refractory diffuse large B-cell lymphoma. Hematology Am Soc Hematol Educ Program 2011;2011:498-505
10. Finnin MS, Donigian JR, Cohen A, et al. Structures of a histone deacetylase homologue bound to the TSA and SAHA inhibitors. Nature 1999;401(6749):188-93
11. Lane AA, Chabner BA. Histone deacetylase inhibitors in cancer therapy. J Clin Oncol 2009;27(32):5459-68
12. Dickinson M, Johnstone RW, Prince HM. Histone deacetylase inhibitors: potential targets responsible for their anti-cancer effect. Invest New Drugs 2010;28(Suppl 1):S3-20
13. Duvic M, Talpur R, Ni X, et al. Phase 2 trial of oral vorinostat (suberoylanilide hydroxamic acid, SAHA) for refractory cutaneous T-cell lymphoma (CTCL). Blood 2007;109(1):31-9
14. Olsen EA, Kim YH, Kuzel TM, et al. Phase IIB multicenter trial of vorinostat in patients with persistent, progressive, or treatment refractory cutaneous T-cell lymphoma. J Clin Oncol 2007;25(21):3109-15
15. Weber DM, Graef T, Hussein M, et al. Phase I trial of vorinostat combined with bortezomib for the treatment of relapsing and/or refractory multiple myeloma. Clin Lymphoma Myeloma Leuk 2012;12(5):319-24
16. Badros A, Burger AM, Philip S, et al. Phase I study of vorinostat in combination with bortezomib for relapsed and refractory multiple myeloma. Clin Cancer Res 2009;15(16):5250-7
17. 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(3):502-7
18. Kirschbaum M, Frankel P, Popplewell L, et al. Phase II study of vorinostat for treatment of relapsed or refractory indolent non-Hodgkin's lymphoma and mantle cell lymphoma. J Clin Oncol 2011;29(9):1198-203
19. Crump M, Coiffier B, Jacobsen ED, et al. Phase II trial of oral vorinostat (suberoylanilide hydroxamic acid) in relapsed diffuse large-B-cell lymphoma. Ann Oncol 2008;19(5):964-9
20. Kirschbaum MH, Goldman BH, Zain JM, et al. A phase 2 study of vorinostat for treatment of relapsed or refractory Hodgkin lymphoma: southwest Oncology Group Study S0517. Leuk Lymphoma 2012;53(2):259-62
21. Schaefer EW, Loaiza-Bonilla A, Juckett M, et al. A phase 2 study of vorinostat in acute myeloid leukemia. Haematologica 2009;94(10):1375-82
22. Walter RB, Medeiros BC, Powell BL, et al. Phase II trial of vorinostat and gemtuzumab ozogamicin as induction and post-remission therapy in older adults with previously untreated acute myeloid leukemia. Haematologica 2012;97(5):739-42
23. Garcia-Manero G, Tambaro FP, Bekele NB, et al. Phase II trial of vorinostat with idarubicin and cytarabine for patients with newly diagnosed acute myelogenous leukemia or myelodysplastic syndrome. J Clin Oncol 2012;30(18):2204-10
24. Quintas-Cardama A, Kantarjian HM, Garcia-Manero G, et al. Impact of combining targeted agents with high-dose cytarabine-based induction chemotherapy on acute myeloid leukemia outcomes: the M.D. Anderson Cancer Center Experience. ASH Annu Meet Abstr 2011;118(21):1539
25. Piekarz RL, Frye R, Turner M, et al. Phase II multi-institutional trial of the histone deacetylase inhibitor romidepsin as monotherapy for patients with cutaneous T-cell lymphoma. J Clin Oncol 2009;27(32):5410-17
26. Whittaker SJ, Demierre MF, Kim EJ, et al. Final results from a multicenter, international, pivotal study of romidepsin in refractory cutaneous T-cell lymphoma. J Clin Oncol 2010;28(29):4485-91
27. Piekarz RL, Frye R, Prince HM, et al. Phase 2 trial of romidepsin in patients with peripheral T-cell lymphoma. Blood 2011;117(22):5827-34
28. Coiffier B, Pro B, Prince HM, et al. Results from a pivotal, open-label, phase II study of romidepsin in relapsed or refractory peripheral T-cell lymphoma after prior systemic therapy. J Clin Oncol 2012;30(6):631-6
29. Fenaux P, DeAngelo DJ, Garcia-Manero G, et al. Phase Ib study of oral panobinostat in combination with 5-azacitidine (5-aza) in patients with myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), or acute myeloid leukemia (AML). ASH Annu Meet Abstr 2010;116(21):4957
30. Fukutomi A, Hatake K, Matsui K, et al. A phase I study of oral panobinostat (LBH589) in Japanese patients with advanced solid tumors. Invest New Drugs 2012;30(3):1096-106
31. Giles F, Fischer T, Cortes J, et al. A phase I study of intravenous LBH589, a novel cinnamic hydroxamic acid analogue histone deacetylase inhibitor, in patients with refractory hematologic malignancies. Clin Cancer Res 2006;12(15):4628-35
32. Clive S, Woo MM, Nydam T, et al. Characterizing the disposition, metabolism, and excretion of an orally active pan-deacetylase inhibitor, panobinostat, via trace radiolabeled 14C material in advanced cancer patients. Cancer Chemother Pharmacol 2012;70(4):513-22
33. Atadja P. Development of the pan-DAC inhibitor panobinostat (LBH589): successes and challenges. Cancer Lett 2009;280(2):233-41
34. Prince HM, Bishton MJ, Johnstone RW. Panobinostat (LBH589): a potent pan-deacetylase inhibitor with promising activity against hematologic and solid tumors. Future Oncol 2009;5(5):601-12
35. Cotto M, Cabanillas F, Tirado M, et al. Epigenetic therapy of lymphoma using histone deacetylase inhibitors. Clin Transl oncol 2010;12(6):401-9
36. Hideshima 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(24):8567-72
37. Ocio 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(5):794-803
38. Vilas-Zornoza A, Agirre X, Abizanda G, et al. Preclinical activity of LBH589 alone or in combination with chemotherapy in a xenogeneic mouse model of human acute lymphoblastic leukemia. Leukemia 2012;26(7):1517-26
39. Sharma S, Beck J, Mita M, et al. A phase I dose-escalation study of intravenous panobinostat in patients with lymphoma and solid tumors. Invest New Drugs 2013; Published online 02 Feb 2013
40. Morita S, Oizumi S, Minami H, et al. Phase I dose-escalating study of panobinostat (LBH589) administered intravenously to Japanese patients with advanced solid tumors. Invest New Drugs 2012;30(5):1950-7
41. Ellis L, Pan Y, Smyth GK, et al. Histone deacetylase inhibitor panobinostat induces clinical responses with associated alterations in gene expression profiles in cutaneous T-cell lymphoma. Clin Cancer Res 2008;14(14):4500-10
42. Deangelo DJ, Spencer A, Bhalla KN, et al. Phase Ia/II, 2-arm, open-label, dose-escalation study of oral panobinostat administered via 2 dosing schedules in patients with advanced hematologic malignancies. Leukemia 2013;Published online 07 Feb 2013
43. Burbury KL, Bishton MJ, Johnstone RW, et al. MLL-aberrant leukemia: complete cytogenetic remission following treatment with a histone deacetylase inhibitor (HDACi). Ann Hematol 2011;90(7):847-9
44. Mascarenhas J, Lu M, Li T, et al. A phase I study of panobinostat (LBH589) in patients with primary myelofibrosis (PMF) and post-polycythaemia vera/essential thrombocythaemia myelofibrosis (post-PV/ET MF). Br J Haematol 2013;1):68-75
45. Ottmann OG, DeAngelo DJ, Garcia-Manero G, et al. Determination of a phase II dose of panobinostat in combination with 5-azacitidine in patients with myelodysplastic syndromes, chronic myelomonocytic leukemia, or acute myeloid leukemia. ASH Annu Meet Abstr 2011;118(21):459
46. Krauter J, Schlenk RF, Schaich M, et al. A phase Ib dose-finding study of oral panobinostat in combination with cytarabine (ara-C) and mitoxantrone as salvage therapy for refractory or relapsed acute myeloid leukemia (AML). ASH Annu Meet Abstr 2010;116(21):3310
47. Hauswald S, Duque-Afonso J, Wagner MM, et al. Histone deacetylase inhibitors induce a very broad, pleiotropic anticancer drug resistance phenotype in acute myeloid leukemia cells by modulation of multiple ABC transporter genes. Clin Cancer Res 2009;15(11):3705-15
48. Fredly H, Stapnes Bjornsen C, Gjertsen BT, Bruserud O. Combination of the histone deacetylase inhibitor valproic acid with oral hydroxyurea or 6-mercaptopurin can be safe and effective in patients with advanced acute myeloid leukaemia-a report of five cases. Hematology (Am Soc Hematol Educ Program) 2010;15(5):338-43
49. Dickinson M, Ritchie D, DeAngelo DJ, et al. Preliminary evidence of disease response to the pan deacetylase inhibitor panobinostat (LBH589) in refractory Hodgkin Lymphoma. Br J Haematol 2009;147(1):97-101
50. Younes A, Sureda A, Ben-Yehuda D, et al. Panobinostat in patients with relapsed/refractory Hodgkin's lymphoma after autologous stem-cell transplantation: results of a phase II study. J Clin Oncol 2012;30(18):2197-203
51. Harrison SJ, Hsu AK, Neeson PJ, et al. Biomarker analysis of pivotal phase II study of oral panobinostat (PAN) in relapsed/refractory Hodgkin lymphoma (HL) patients following autologous stem cell transplant (ASCT). ASCO Meet Abstr 2011;29(15-Suppl):8046
52. Younes A, Pro B, Fanale M, et al. Isotype-selective HDAC inhibitor MGCD0103 decreases serum TARC concentrations and produces clinical responses in heavily pretreated patients with relapsed classical hodgkin lymphoma (HL). ASH Annu Meet Abstr 2007;110(11):2566
53. Duvic M, Dummer R, Becker JC, et al. Panobinostat activity in both bexarotene-exposed and-naive patients with refractory cutaneous T-cell lymphoma: results of a phase II trial. Eur J Cancer 2013;49(2):386-94
54. Prince HM, Dickinson M. Romidepsin for cutaneous T-cell lymphoma. Clin Cancer Res 2012;18(13):3509-15
55. Ghobrial IM, Campigotto F, Murphy TJ, et al. Results of a phase 2 trial of the single-agent histone deacetylase inhibitor panobinostat in patients with relapsed/refractory Waldenstrom macroglobulinemia. Blood 2013;121(8):1296-303
56. Flinn IW, Lang E, Raefsky E, et al. Preliminary results of a phase II trial of panobinostat (LBH589) in refractory myelodysplastic syndromes (MDS) patients. ASH Annu Meet Abstr 2010;116(21):4015
57. Zhang L, Lebwohl D, Masson E, et al. Clinically relevant QTc prolongation is not associated with current dose schedules of LBH589 (panobinostat). J Clin Oncol 2008;26(2):332-3
58. Bruserud O, Stapnes C, Ersvaer E, et al. Histone deacetylase inhibitors in cancer treatment: a review of the clinical toxicity and the modulation of gene expression in cancer cell. Curr Pharm Biotechnol 2007;8(6):388-400
59. Bishton MJ, Harrison SJ, Martin BP, et al. Deciphering the molecular and biologic processes that mediate histone deacetylase inhibitor-induced thrombocytopenia. Blood 2011;117(13):3658-68
60. Pilatrino C, Cilloni D, Messa E, et al. Increase in platelet count in older, poor-risk patients with acute myeloid leukemia or myelodysplastic syndrome treated with valproic acid and all-trans retinoic acid. Cancer 2005;104(1):101-9 Available from: www.clinicaltrials.gov
61. Catley 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(10):3441-9
62. Tefferi A, Litzow MR, Pardanani A. Long-term outcome of treatment with ruxolitinib in myelofibrosis. N Engl J Med 2011;365(15):1455-7
63. Kalff A, Shortt J, Farr J, et al. Laboratory tumor lysis syndrome complicating LBH589 therapy in a patient with acute myeloid leukaemia. Haematologica 2008;93(1):e16-17
64. Dawson MA, Kouzarides T, Huntly BJ. Targeting epigenetic readers in cancer. N Engl J Med 2012;367(7):647-57