An Expanded Treatment Protocol of Panobinostat Plus Bortezomib and Dexamethasone in Patients With Previously Treated Myeloma |
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Authors: | Vincent L Hansen Morton Coleman Stephanie Elkins Jeffrey P Letzer Moshe Yair Levy Lasika Seneviratne Jessica Rine Marina White Emil T Kuriakose |
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Institution: | 1. Northern Utah Associates, Ogden, UT;2. Weill Cornell Medicine, Clinical Research Alliance, New York, NY;3. Cancer Institute, University of Mississippi Medical Center, Jackson, MS;4. MidMichigan Health, Midland, MI;5. Texas Oncology–Baylor Charles A. Sammons Cancer Center, Dallas, TX;6. SCORA Network, LLC, Torrance, CA;7. Novartis Pharmaceuticals Corporation, East Hanover, NJ |
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Abstract: | BackgroundPanobinostat was recently approved by the US Food and Drug Administration and European Commission in combination with bortezomib and dexamethasone for patients with multiple myeloma who have received ≥ 2 regimens, including bortezomib and an immunomodulatory drug. The PANEX (panobinostat expansion) treatment protocol provided access to panobinostat and gathered additional safety data before commercial availability.Patients and MethodsIn treatment phase 1, patients received panobinostat 20 mg 3 times per week plus bortezomib 1.3 mg/m2 twice weekly with dexamethasone 20 mg on the days of and after bortezomib treatment. Patients with no change or better in treatment phase 1 proceeded to treatment phase 2, when bortezomib was reduced to once weekly. Unlike in the phase III trial, PANORAMA-1 (panobinostat or placebo with bortezomib and dexamethasone in patients with relapsed multiple myeloma), bortezomib could be administered either subcutaneously or intravenously.ResultsThirty-nine patients with a median number of previous treatments of 4 (range, 1-12) were enrolled; most received subcutaneous bortezomib (87%). The overall response rate (partial response or better) was 56%. Grade 3/4 adverse events included thrombocytopenia (47%), fatigue (31%), dehydration (26%), and diarrhea (18%). Among the patients who received subcutaneous bortezomib, relatively low rates of peripheral neuropathy (all grade, 15%) and notable grade 3/4 adverse events (thrombocytopenia, 47%; diarrhea, 12%) were observed.ConclusionOverall, data from the PANEX trial support regulatory approval of panobinostat plus bortezomib and dexamethasone and suggest the potential tolerability benefits of subcutaneous bortezomib in this regimen. |
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Keywords: | Epigenetics Histone deacetylase inhibitor PANORAMA Safety Subcutaneous BTZ |
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