title: Phase II multicentre trial of oral quisinostat, a histone deacetylase inhibitor, in patients with previously treated stage IB-IVA mycosis fungoides/Sézary syndrome.
abstract: BACKGROUND
  Quisinostat is a hydroxamate, second-generation, orally available pan-histone deacetylase inhibitor.
  
  
  OBJECTIVE
  To evaluate the efficacy and safety of oral quisinostat in patients with previously treated cutaneous T-cell lymphoma (CTCL).
  
  
  METHODS
  Patients received quisinostat 8 mg or 12 mg on days 1, 3 and 5 of each week in 21-day treatment cycles. Primary efficacy end point was cutaneous response rate (RR) based on the modified Severity Weighted Assessment Tool (mSWAT). Secondary end points included global RR, duration of response (DOR) in skin, progression-free survival (PFS), pruritus relief, safety and pharmacodynamic markers.
  
  
  RESULTS
  Eight of 26 (25 evaluable) patients achieved ≥ 50% reduction in mSWAT score at least once, with confirmed cutaneous response in six (RR 24%). There was a low global RR of 8%. DOR in skin ranged from 2·8 to 6·9 months. Median PFS was 5·1 months. Pruritus relief was more frequent in cutaneous responders (67%) than nonresponders (32%). Serial tumour biopsies revealed an increase in acetylated tubulin, indicating a target effect of histone deacetylase 6. Twenty-one of 26 (81%) patients were withdrawn from the study before or at clinical cut-off; five (19%) continued to receive treatment with quisinostat. The most common drug-related adverse events were nausea, diarrhoea, asthenia, hypertension, thrombocytopenia and vomiting. Grade 3 drug-related adverse events included hypertension, lethargy, pruritus, chills, hyperkalaemia and pyrexia.
  
  
  CONCLUSIONS
  Quisinostat 12 mg three times weekly is active in the treatment of patients with relapsed or refractory CTCL, with an acceptable safety profile. Combination therapy with other drugs active in CTCL may be appropriate.
authors.affiliation: St John's Institute of Dermatology, Guy's and St Thomas' NHS Foundation Trust, London, U.K.
authors.forename: F
authors.initials: F
authors.lastname: Child
authors.affiliation: Department of Dermatology, 12 de Octubre Hospital, Institute i+12, Medical School, Complutense University, Madrid, Spain.
authors.forename: P L
authors.initials: PL
authors.lastname: Ortiz-Romero
authors.affiliation: Portuguese Institute of Oncology, Lisbon, Portugal.
authors.forename: R
authors.initials: R
authors.lastname: Alvarez
authors.affiliation: Department of Dermatology, Saint-Louis Hospital, Paris 7 University, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Bagot
authors.affiliation: Department of Dermatology, Johannes Wesling Medical Center, Minden, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Stadler
authors.affiliation: Department of Dermatology, University Hospital of Schleswig-Holstein, Kiel, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Weichenthal
authors.affiliation: Department of Dermatology, Hospital de Santo António - Centro Hospitalar do Porto, Porto, Portugal.
authors.forename: R
authors.initials: R
authors.lastname: Alves
authors.affiliation: Department of Medical Sciences, Dermatologic Clinic, University of Turin, Turin, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Quaglino
authors.affiliation: Department of Dermatology, University Hospital of Bordeaux, Bordeaux, France.
authors.forename: M
authors.initials: M
authors.lastname: Beylot-Barry
authors.affiliation: Manchester Academic Health Science Centre, Christie Hospital, Manchester, U.K.
authors.forename: R
authors.initials: R
authors.lastname: Cowan
authors.affiliation: School of Medicine, Department of Dermatology, University of Pittsburgh, Pittsburgh, PA, U.S.A.
authors.forename: L J
authors.initials: LJ
authors.lastname: Geskin
authors.affiliation: Department of Dermatology, University General Hospital, Valencia, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Pérez-Ferriols
authors.affiliation: Janssen Research & Development, Beerse, Belgium.
authors.forename: P
authors.initials: P
authors.lastname: Hellemans
authors.affiliation: Janssen Research & Development, Titusville, NJ, U.S.A.
authors.forename: Y
authors.initials: Y
authors.lastname: Elsayed
authors.affiliation: Janssen Research & Development, Titusville, NJ, U.S.A.
authors.forename: C
authors.initials: C
authors.lastname: Phelps
authors.affiliation: Janssen Research & Development, Spring House, PA, U.S.A.
authors.forename: A
authors.initials: A
authors.lastname: Forslund
authors.affiliation: Janssen Pharmaceutical K.K., Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kamida
authors.affiliation: Institute of Hematology 'Seràgnoli', University of Bologna, Bologna, Italy.
authors.forename: P L
authors.initials: PL
authors.lastname: Zinzani
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D014408:Biomarkers, Tumor / Q000378:metabolism; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D056572:Histone Deacetylase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009182:Mycosis Fungoides / Q000188:drug therapy*; D011537:Pruritus / Q000517:prevention & control; D019233:Retreatment; D012751:Sezary Syndrome / Q000188:drug therapy*; D012878:Skin Neoplasms / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; C541788:quisinostat