title: A phase II study of the histone deacetylase inhibitor panobinostat (LBH589) in pretreated patients with small-cell lung cancer.
abstract: BACKGROUND
  In vitro data suggest that panobinostat (LBH589), a pan-deacetylase inhibitor, may add therapeutic benefit in the treatment of small-cell lung cancer (SCLC) with regression of tumors.
  
  
  METHODS
  This multicenter, nonrandomized phase 2 trial was designed to evaluate antitumor activity of LBH589 in patients with previously treated SCLC. Patients received LBH589 administered intravenously at a dose of 20 mg/mq (days 1-8) every 21 days.
  
  
  RESULTS
  A total of 21 patients with extensive- or limited-stage SCLC were enrolled. Patients received a median of two cycles (range, 1-6). LBH589 was well tolerated, and the most common toxicities were grade 1 to 2 gastrointestinal disorders (nausea 38%, diarrhea 24%, vomiting 19%), grade 1 to 2 thrombocytopenia (14.3%). Of 19 patients evaluable for efficacy, two cases showed shrinkages more than 30% at first assessment, with time to progression of 14 and 21 weeks, respectively, and there were three long disease stabilizations of 12, 10, and 13 weeks. The study was prematurely closed because of a lack of activity.
  
  
  CONCLUSIONS
  This is the first report of a pan-deacetylase inhibitor inducing tumor shrinkage and sustained stable disease in SCLC. We believe that although the trial was prematurely discontinued, modest clinical activity of LBH589 combined with a favorable safety profile in pretreated SCLC patients was observed, which warrants further exploration of the potential contribution of LBH589 in other trials.
authors.affiliation: Department of Pulmonary-Oncology, San Camillo Hospital, Rome, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: de Marinis
authors.forename: Akin
authors.initials: A
authors.lastname: Atmaca
authors.forename: Marcello
authors.initials: M
authors.lastname: Tiseo
authors.forename: Libero
authors.initials: L
authors.lastname: Giuffreda
authors.forename: Antonio
authors.initials: A
authors.lastname: Rossi
authors.forename: Vittorio
authors.initials: V
authors.lastname: Gebbia
authors.forename: Chiara
authors.initials: C
authors.lastname: D'Antonio
authors.forename: Laura
authors.initials: L
authors.lastname: Dal Zotto
authors.forename: Salah-Eddin
authors.initials: SE
authors.lastname: Al-Batran
authors.forename: Silvia
authors.initials: S
authors.lastname: Marsoni
authors.forename: Martin
authors.initials: M
authors.lastname: Wolf
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; 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*; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D000077767:Panobinostat; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D007211:Indoles; D000077767:Panobinostat