title: VANTAGE 095: An International, Multicenter, Open-Label Study of Vorinostat (MK-0683) in Combination With Bortezomib in Patients With Relapsed and Refractory Multiple Myeloma.
abstract: The present global, open-label, single-arm, multicenter, phase IIb study was designed to determine the efficacy and tolerability of oral vorinostat combined with standard doses of bortezomib in patients with multiple myeloma considered refractory to novel myeloma agents.
  
  
  
  Eligible patients were age ≥ 18 years, had received ≥ 2 previous regimens, had disease refractory to ≥ 1 previous bortezomib-containing regimen, and had received ≥ 1 dose of an immunomodulatory drug (thalidomide or lenalidomide)-based regimen. The patients received 21-day cycles of bortezomib (1.3 mg/m(2) intravenously on days 1, 4, 8, and 11) plus oral vorinostat (400 mg/d on days 1-14). Oral dexamethasone, 20 mg, on the day of and the day after each dose of bortezomib could be added for patients with progressive disease after 2 cycles or no change after 4 cycles. The primary endpoint was the objective response rate.
  
  
  
  The objective response rate was 11.3% (95% confidence interval, 6.6%-17.7%), and the median duration of response was 211 days (range, 64-550 days). The median overall survival duration was 11.2 months (95% confidence interval, 8.5-14.4 months), with a 2-year survival rate of 32%. The frequently reported adverse events were thrombocytopenia (69.7%), nausea (57.0%), diarrhea (53.5%), anemia (52.1%), and fatigue (48.6%); the overall safety profile was consistent with that of bortezomib and vorinostat.
  
  
  
  The combination of vorinostat and bortezomib is active in patients with multiple myeloma refractory to novel treatment modalities and offers a new therapeutic option for this difficult-to-treat patient population (ClinicalTrials.gov identifier, NCT00773838).
authors.affiliation: Myeloma Division, Hackensack University Medical Center, Hackensack, NJ. Electronic address: dsiegel@hackensackumc.org.
authors.forename: David S
authors.initials: DS
authors.lastname: Siegel
authors.affiliation: Department of Therapeutics, University of Athens, Athens, Greece.
authors.forename: Meletios
authors.initials: M
authors.lastname: Dimopoulos
authors.affiliation: Mount Sinai Medical Center, New York, NY.
authors.forename: Sundar
authors.initials: S
authors.lastname: Jagannath
authors.affiliation: Universitätsklinikum Heidelberg, Heidelberg, Germany.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Goldschmidt
authors.affiliation: Bone Marrow Transplant Clinical Hematology Unit, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia.
authors.forename: Simon
authors.initials: S
authors.lastname: Durrant
authors.affiliation: Emory University School of Medicine, Atlanta, GA.
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Kaufman
authors.affiliation: Service des Maladies du Sang, University of Lille, Lille, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Leleu
authors.affiliation: Hematology Division, Chaim Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: Arnon
authors.initials: A
authors.lastname: Nagler
authors.affiliation: Universitair Ziekenhuis Gent, Ghent, Belgium.
authors.forename: Fritz
authors.initials: F
authors.lastname: Offner
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Graef
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ.
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Eid
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Houp
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ.
authors.forename: Christine
authors.initials: C
authors.lastname: Gause
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ.
authors.forename: Scott
authors.initials: S
authors.lastname: Vuocolo
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA.
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Anderson
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000069286:Bortezomib / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage; D008297:Male; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D012008:Recurrence; D019233:Retreatment; D016019:Survival Analysis; D016896:Treatment Outcome; D000077337:Vorinostat
chemical_list: D006877:Hydroxamic Acids; D000077337:Vorinostat; D000069286:Bortezomib
keywords: Combination therapy; Efficacy; Histone deacetylase inhibitor; Proteasome inhibitor; Safety