Document Detail


The effect of food on the bioavailability of panobinostat, an orally active pan-histone deacetylase inhibitor, in patients with advanced cancer.
MedLine Citation:
PMID:  22057852     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: 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:
Geoffrey I Shapiro; Richard Frank; Uday B Dandamudi; Thomas Hengelage; Lily Zhao; Lucien Gazi; Maria Grazia Porro; Margaret M Woo; Lionel D Lewis
Publication Detail:
Type:  Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't     Date:  2011-11-06
Journal Detail:
Title:  Cancer chemotherapy and pharmacology     Volume:  69     ISSN:  1432-0843     ISO Abbreviation:  Cancer Chemother. Pharmacol.     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-01-25     Completed Date:  2012-03-20     Revised Date:  2013-07-01    
Medline Journal Info:
Nlm Unique ID:  7806519     Medline TA:  Cancer Chemother Pharmacol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  555-62     Citation Subset:  IM    
Affiliation:
Early Drug Development Center, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
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MeSH Terms
Descriptor/Qualifier:
Administration, Oral
Adult
Aged
Aged, 80 and over
Area Under Curve
Biological Availability
Cross-Over Studies
Diet, High-Fat
Drug Administration Schedule
Eating
Fasting
Fatigue / chemically induced
Female
Food*
Food-Drug Interactions
Histone Deacetylase Inhibitors / administration & dosage,  adverse effects,  pharmacokinetics*
Humans
Hydroxamic Acids / administration & dosage,  adverse effects,  pharmacokinetics*
Indoles
Male
Metabolic Clearance Rate
Middle Aged
Nausea / chemically induced
Neoplasms / drug therapy,  metabolism*,  pathology
Treatment Outcome
Vomiting / chemically induced
Grant Support
ID/Acronym/Agency:
P30 CA023108/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Histone Deacetylase Inhibitors; 0/Hydroxamic Acids; 0/Indoles; 0/panobinostat

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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