title: Quisinostat, bortezomib, and dexamethasone combination therapy for relapsed multiple myeloma.
abstract: The maximum tolerated dose (MTD) of quisinostat + bortezomib + dexamethasone in patients with relapsed multiple myeloma was evaluated in a phase-1b, open-label, multicenter, '3 + 3' dose-escalation study. Patients received escalating doses of oral quisinostat (6 mg [n = 3], 8 mg [n = 3], 10 mg [n = 6], and 12 mg [n = 6] on days 1, 3, and 5/week) plus subcutaneous bortezomib (1.3 mg/m(2)) and oral dexamethasone (20 mg) in cycles of 21 (cycles 1-8) or 35 d (cycles 9-11) until MTD was determined. No dose-limiting toxicities were reported in 6/8 mg groups except ventricular fibrillation (Grade 4 cardiac arrest, n = 1 [10 mg] cycle 6) and clinically significant cardiac toxicities (Grade 3 QTc prolongation, Grade 3 atrial fibrillation, n = 2 [12 mg]). Thrombocytopenia (n = 11), asthenia (n = 10), and diarrhea (n = 12) were most common adverse events. Overall, 88.2% patients achieved treatment response, median duration of response, and median progression-free survival were 9.4 and 8.2 months, respectively. The MTD of quisinostat was established as 10 mg thrice weekly oral dose with bortezomib + dexamethasone.
authors.affiliation: a Hôpital Hôtel Dieu, CHU Nantes, Service D' Hématologie , Nantes , France ;
authors.forename: Philippe
authors.initials: P
authors.lastname: Moreau
authors.affiliation: b Hôpital Claude Huriez, CHRU De Lille, Service Des Maladies Du Sang , Lille , France ;
authors.forename: Thierry
authors.initials: T
authors.lastname: Facon
authors.affiliation: a Hôpital Hôtel Dieu, CHU Nantes, Service D' Hématologie , Nantes , France ;
authors.forename: Cyrille
authors.initials: C
authors.lastname: Touzeau
authors.affiliation: c CHRU Bretonneau, Centre H. Kaplan, Service Hématologie , Tours , France ;
authors.forename: Lotfi
authors.initials: L
authors.lastname: Benboubker
authors.affiliation: c CHRU Bretonneau, Centre H. Kaplan, Service Hématologie , Tours , France ;
authors.forename: Martine
authors.initials: M
authors.lastname: Delain
authors.affiliation: d Division of Janssen-Cilag , Quintiles, providing services on Behalf of Janssen Research & Development , Issy-Les-Moulineaux , France ;
authors.forename: Julie
authors.initials: J
authors.lastname: Badamo-Dotzis
authors.affiliation: e Janssen Research & Development , Raritan , NJ , USA ;
authors.forename: Charles
authors.initials: C
authors.lastname: Phelps
authors.affiliation: f Janssen Research & Development , Beerse , Belgium.
authors.forename: Christopher
authors.initials: C
authors.lastname: Doty
authors.affiliation: f Janssen Research & Development , Beerse , Belgium.
authors.forename: Hans
authors.initials: H
authors.lastname: Smit
authors.affiliation: f Janssen Research & Development , Beerse , Belgium.
authors.forename: Nele
authors.initials: N
authors.lastname: Fourneau
authors.affiliation: f Janssen Research & Development , Beerse , Belgium.
authors.forename: Ann
authors.initials: A
authors.lastname: Forslund
authors.affiliation: f Janssen Research & Development , Beerse , Belgium.
authors.forename: Peter
authors.initials: P
authors.lastname: Hellemans
authors.affiliation: b Hôpital Claude Huriez, CHRU De Lille, Service Des Maladies Du Sang , Lille , France ;
authors.forename: Xavier
authors.initials: X
authors.lastname: Leleu
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers; D000069286:Bortezomib / Q000008:administration & dosage; D003907:Dexamethasone / Q000008:administration & dosage; D016903:Drug Monitoring; D005260:Female; D056572:Histone Deacetylase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage; D053208:Kaplan-Meier Estimate; D008297:Male; D020714:Maximum Tolerated Dose; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D009360:Neoplastic Cells, Circulating; D012008:Recurrence; D019233:Retreatment; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; C541788:quisinostat; D000069286:Bortezomib; D003907:Dexamethasone
keywords: Bortezomib; dexamethasone; histone deacetylase inhibitor; multiple myeloma; quisinostat