title: The effect of food on the bioavailability of panobinostat, an orally active pan-histone deacetylase inhibitor, in patients with advanced cancer.
abstract: OBJECTIVE
  Panobinostat is a novel oral pan-deacetylase inhibitor with promising anti-cancer activity. The study aimed to determine the influence of food on the oral bioavailability of panobinostat.
  
  
  METHODS
  This multicenter study consisted of a randomized, three-way crossover, food-effect study period (cycle 1) followed by single-agent panobinostat continual treatment phase in patients with advanced cancer. Patients received panobinostat 20 mg twice weekly, and panobinostat pharmacokinetics was investigated on days 1, 8, and 15 with a randomly assigned sequence of three prandial states (fasting, high-fat, and normal breakfast).
  
  
  RESULTS
  Thirty-six patients were assessed for the food effect on pharmacokinetics and safety in cycle 1, after which 29 patients continued treatment, receiving single-agent panobinostat. Safety and antitumor activity were assessed during the extension period. Panobinostat systemic exposure was marginally reduced (14-16%) following food [geometric mean ratio (GMR) of the AUC(0-∞)/high-fat breakfast/fasting, 0.84 (90% confidence interval {CI}, 0.74-0.96); normal breakfast/fasting, 0.86 (90% CI, 0.75-1.00)], and interpatient variability (coefficient of variation, 59%) remained essentially unchanged with or without food. Panobinostat C                            (max) was reduced by 44% (high-fat) and 36% (normal) with median T                            (max) prolonged by 1-1.5 h following food. Panobinostat was well tolerated, with thrombocytopenia, fatigue, nausea, and vomiting as common adverse events, and demonstrated antitumor activity with one patient with a partial response and six patients with stable disease as best response.
  
  
  CONCLUSIONS
  Food produced minor changes in oral panobinostat exposure; thus, panobinostat can be given without regard to food intake in future clinical studies.
authors: Early Drug Development Center, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
authors: Geoffrey I
authors: GI
authors: Shapiro
authors: Richard
authors: R
authors: Frank
authors: Uday B
authors: UB
authors: Dandamudi
authors: Thomas
authors: T
authors: Hengelage
authors: Lily
authors: L
authors: Zhao
authors: Lucien
authors: L
authors: Gazi
authors: Maria Grazia
authors: MG
authors: Porro
authors: Margaret M
authors: MM
authors: Woo
authors: Lionel D
authors: LD
authors: Lewis
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D001682:Biological Availability; D018592:Cross-Over Studies; D059305:Diet, High-Fat; D004334:Drug Administration Schedule; D004435:Eating; D005215:Fasting; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D005502:Food; D018565:Food-Drug Interactions; D056572:Histone Deacetylase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D007211:Indoles; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D000077767:Panobinostat; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced
chemical_list: D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D007211:Indoles; D000077767:Panobinostat