Role of histone deacetylase inhibitors in relapsed refractory multiple myeloma: A focus on vorinostat and panobinostat Journal Article
| Authors: | Afifi, S.; Michael, A.; Azimi, M.; Rodriguez, M.; Lendvai, N.; Landgren, O. |
| Article Title: | Role of histone deacetylase inhibitors in relapsed refractory multiple myeloma: A focus on vorinostat and panobinostat |
| Abstract: | Multiple myeloma is a neoplastic plasma cell disorder that is characterized by clonal proliferation of plasma cells in the bone marrow, monoclonal protein in the blood and/or urine, and associated organ dysfunction and biomarkers. There have been multiple recent advances in the relapsed and refractory setting. Major steps forward include the introduction of proteasome inhibitors (bortezomib and carfilzomib) and immunomodulatory drugs (thalidomide, lenalidomide, and pomalidomide) in various combinations. These drugs have changed the management of multiple myeloma and have extended overall survival in the past decade. Established curative therapy is not yet available for patients diagnosed with multiple myeloma, supporting the development of new treatment targets. Histone deacetylase inhibitors have multiple proposed mechanisms of action in the treatment of multiple myeloma. Both vorinostat and panobinostat have demonstrated some activity against multiple myeloma, and due to the benefits reported with panobinostat, the U.S. Food and Drug Administration has recently approved the drug for the treatment of relapsed and refractory multiple myeloma. In this article, we describe the pharmacology, efficacy, and toxicity profile of vorinostat and panobinostat and their possible place in therapy. © 2015 Pharmacotherapy Publications, Inc. |
| Keywords: | treatment response; unclassified drug; overall survival; histone deacetylase inhibitor; lenalidomide; fatigue; neutropenia; cancer recurrence; doxorubicin; cancer combination chemotherapy; diarrhea; drug efficacy; drug potentiation; drug safety; monotherapy; treatment; protein bcl 2; apoptosis; bortezomib; proteasome inhibitor; multiple cycle treatment; multiple myeloma; anemia; nausea; thrombocytopenia; vomiting; dexamethasone; melphalan; kidney failure; caspase 3; enzyme activity; protein bcl xl; dna methylation; drug dose escalation; tumor lysis syndrome; hypokalemia; drug mechanism; epigenetics; death receptor 4; death receptor 5; tumor necrosis factor related apoptosis inducing ligand; vorinostat; histone deacetylase inhibitors; drug clearance; caspase 9; upregulation; hot flush; drug bioavailability; drug metabolism; drug blood level; gastrointestinal disease; panobinostat; romidepsin; hematologic disease; belinostat; hypocalcemia; carfilzomib; drug indication; refractory; cytochrome p450 2d6; clinical trial (topic); phase 3 clinical trial (topic); cytochrome p450 3a4; phase 1 clinical trial (topic); histone modification; relapsed; hdac; mitochondrial permeability transition pore; aggresome; g1 phase cell cycle checkpoint; ricolinostat; human; article; ar 42; multiple myeloma cell line; cytochrome p450 2c19 |
| Journal Title: | Pharmacotherapy |
| Volume: | 35 |
| Issue: | 12 |
| ISSN: | 0277-0008 |
| Publisher: | John Wiley & Sons |
| Date Published: | 2015-12-01 |
| Start Page: | 1173 |
| End Page: | 1188 |
| Language: | English |
| DOI: | 10.1002/phar.1671 |
| PROVIDER: | scopus |
| PUBMED: | 26684557 |
| PMCID: | PMC4995883 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 3 February 2016 -- Source: Scopus |
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