title: Panobinostat activity in both bexarotene-exposed and -naïve patients with refractory cutaneous T-cell lymphoma: results of a phase II trial.
abstract: BACKGROUND
  Panobinostat is a potent, oral pan-deacetylase inhibitor (pan-DACi) that increases the acetylation of proteins involved in multiple oncogenic pathways. Here, panobinostat is studied in bexarotene-exposed and -naïve patients with refractory cutaneous T-cell lymphoma (CTCL).
  
  
  METHODS
  Patients with CTCL subtypes mycosis fungoides and Sézary syndrome who received ⩾2 prior systemic therapy regimens received panobinostat (20mg) three times every week. The primary objective was overall response rate (ORR) as determined by a combined evaluation of skin disease and involvement of lymph node and viscera. Disease progression was defined as an unconfirmed, ⩾25% increase in modified Severity Weighted Assessment Tool (mSWAT) compared with nadir.
  
  
  RESULTS
  Seventy-nine bexarotene-exposed and 60 bexarotene-naïve patients were enrolled. Reductions in baseline mSWAT scores were observed in 103 patients (74.1%). The ORR was 17.3% in all patients in the primary analysis (15.2% and 20.0% in the bexarotene-exposed and -naïve groups, respectively). The median progression-free survival was 4.2 and 3.7 months in the bexarotene-exposed and -naïve groups, respectively. The median duration of response was 5.6 months in the bexarotene-exposed patients and was not reached at data cutoff in the bexarotene-naïve patients. Additional responses were observed when less-stringent progression criteria were used. The most common adverse events were thrombocytopenia, diarrhoea, fatigue and nausea. Thrombocytopenia and neutropenia were the only grade 3/4 adverse events in >5% of patients and were manageable.
  
  
  CONCLUSIONS
  Despite a very conservative definition of disease progression, panobinostat demonstrated activity with a manageable safety profile in bexarotene-exposed and -naïve CTCL patients. ClinicalTrials.gov Identifier: NCT00425555.
authors.affiliation: MD Anderson Cancer Center, Houston, TX, USA. mduvic@mdanderson.org
authors.forename: Madeleine
authors.initials: M
authors.lastname: Duvic
authors.forename: Reinhard
authors.initials: R
authors.lastname: Dummer
authors.forename: Jürgen C
authors.initials: JC
authors.lastname: Becker
authors.forename: Nicolas
authors.initials: N
authors.lastname: Poulalhon
authors.forename: Pablo
authors.initials: P
authors.lastname: Ortiz Romero
authors.forename: Maria
authors.initials: M
authors.lastname: Grazia Bernengo
authors.forename: Celeste
authors.initials: C
authors.lastname: Lebbé
authors.forename: Chalid
authors.initials: C
authors.lastname: Assaf
authors.forename: Margaret
authors.initials: M
authors.lastname: Squier
authors.forename: Denise
authors.initials: D
authors.lastname: Williams
authors.forename: Miriam
authors.initials: M
authors.lastname: Marshood
authors.forename: Feng
authors.initials: F
authors.lastname: Tai
authors.forename: H Miles
authors.initials: HM
authors.lastname: Prince
mesh_terms: D016588:Anticarcinogenic Agents / Q000008:administration & dosage*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000077610:Bexarotene; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D056572:Histone Deacetylase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D006877:Hydroxamic Acids / Q000009:adverse effects / Q000627:therapeutic use*; D007211:Indoles / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009182:Mycosis Fungoides / Q000188:drug therapy* / Q000473:pathology; D000077767:Panobinostat; D012751:Sezary Syndrome / Q000188:drug therapy* / Q000473:pathology; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage*
chemical_list: D016588:Anticarcinogenic Agents; D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D007211:Indoles; D013764:Tetrahydronaphthalenes; D000077767:Panobinostat; D000077610:Bexarotene