Panobinostat: A histone deacetylase inhibitor for the treatment of relapsed or refractory multiple myeloma
| Autor: | Ashton E. Beggs, Kristy Wahaib, Leela Kodali, Hope E. Campbell, Patrick D. Ford |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Oncology medicine.medical_specialty Indoles Pharmacology Hydroxamic Acids Dexamethasone Bortezomib 03 medical and health sciences chemistry.chemical_compound Clinical Trials Phase II as Topic 0302 clinical medicine Recurrence Panobinostat Internal medicine Antineoplastic Combined Chemotherapy Protocols medicine Humans Adverse effect Multiple myeloma business.industry Health Policy Hazard ratio medicine.disease Histone Deacetylase Inhibitors Regimen Treatment Outcome 030104 developmental biology Clinical Trials Phase III as Topic chemistry 030220 oncology & carcinogenesis Pharmacodynamics Multiple Myeloma business medicine.drug |
| Zdroj: | American Journal of Health-System Pharmacy. 73:441-450 |
| ISSN: | 1535-2900 1079-2082 |
| DOI: | 10.2146/ajhp150487 |
| Popis: | Purpose The mechanism of action, pharmacodynamics, pharmacokinetics, clinical efficacy, interaction potential, adverse effects, and place in therapy of panobinostat are reviewed. Summary Panobinostat (Farydak, Novartis) is a novel pan-deacetylase inhibitor approved for use in combination with bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma (RRMM) who have received at least two regimens containing an immunomodulatory drug and bortezomib. National Comprehensive Cancer Network (NCCN) guidelines recommend the use of panobinostat plus bortezomib and dexamethasone as a preferred regimen for previously treated multiple myeloma (MM). A Phase III trial comparing panobinostat or placebo use in combination with bortezomib and dexamethasone demonstrated improved median progression-free survival in the panobinostat group (11.99 months [95% CI, 10.33–12.94 months] versus 8.08 months [95% CI, 7.56–9.23 months]; hazard ratio, 0.63 [95% CI, 0.52–0.76]; p < 0.0001), as well as a significantly higher rate of complete or near complete response (27.6% [95% CI, 23.2–32.4%] versus 15.7% [95% CI, 12.2–19.8%]; p = 0.00006). Common grade 3 or 4 laboratory abnormalities and adverse events associated with panobinostat include thrombocytopenia, lymphopenia, diarrhea, asthenia, fatigue, and peripheral neuropathy. Conclusion Panobinostat is a promising alternative to well-studied, NCCN-recommended regimens for the treatment of RRMM. It has demonstrated efficacy when used in combination with bortezomib and dexamethasone for the treatment of patients with MM who have received at least two prior regimens including bortezomib and an immunomodulatory agent. Despite the observed benefits, concern regarding toxicity may limit panobinostat use in practice. |
| Databáze: | OpenAIRE |
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