Erschienen in:
01.02.2012 | Clinical Trial Report
The effect of food on the bioavailability of panobinostat, an orally active pan-histone deacetylase inhibitor, in patients with advanced cancer
verfasst von:
Geoffrey I. Shapiro, Richard Frank, Uday B. Dandamudi, Thomas Hengelage, Lily Zhao, Lucien Gazi, Maria Grazia Porro, Margaret M. Woo, Lionel D. Lewis
Erschienen in:
Cancer Chemotherapy and Pharmacology
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Ausgabe 2/2012
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Abstract
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 AUC0−∞/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.