Margaret M. Woo

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Histone deacetylase inhibitors have demonstrated anticancer activity against a range of tumors. We aimed to define the maximum tolerated dose, toxicity, activity, and pharmacokinetics of oral panobinostat, a pan-deacetylase inhibitor, alone and in combination with docetaxel for the treatment of castration-resistant prostate cancer (CRPC). Sixteen patients(More)
Elucidating the metabolic profile of anticancer agent panobinostat is essential during drug development. Disposition, metabolism, and excretion profiles were characterized using trace radiolabeled 14C-panobinostat in four patients with advanced cancer. Oral 14C-panobinostat was administered and serial blood, plasma, and excreta samples were collected up to(More)
Panobinostat is partly metabolized by CYP3A4 in vitro. This study evaluated the effect of a potent CYP3A inhibitor, ketoconazole, on the pharmacokinetics and safety of panobinostat. Patients received a single panobinostat oral dose on day 1, followed by 4 days wash-out period. On days 5–9, ketoconazole was administered. On day 8, a single panobinostat dose(More)
Mechanisms responsible for the accumulation of low-density lipoprotein (LDL) were investigated in a new model, the perfused hamster aorta. To do this, we developed a method to study LDL flux in real time in individually perfused arteries; each artery served as its own control. Using quantitative fluorescence microscopy, the rates of LDL accumulation and(More)
Pamidronate is a second-generation bisphosphonate that undergoes negligible biodegradation and is eliminated exclusively by renal excretions. Nineteen cancer patients were stratified according to baseline creatinine clearance (Clcr): group I, Clcr > 90 mL/min (n = 6); group II, Clcr 61 mL/min to 90 mL/min (n = 6); group III, Clcr 30 mL/min to 60 mL/min (n =(More)
Panobinostat is a potent oral pan-deacetylase inhibitor with promising clinical activity in hematologic malignancies. Panobinostat was shown to inhibit CYP2D6 activity in vitro; thus understanding the magnitude of the potential clinical inhibition of panobinostat on co-medications that are CYP2D6 substrates becomes important. This study evaluated the(More)
To determine the inhibitory potency of letrozole and its main human metabolite, 4,4′-methanol-bisbenzonitrile, on the activities of eight cytochrome P450 (CYP) enzymes. Letrozole and its metabolite were incubated with human liver microsomes (HLMs) (or expressed CYP isoforms) and NADPH in the absence (control) and presence of the test inhibitor. Letrozole(More)
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. This multicenter study consisted of a randomized, three-way crossover, food-effect study period (cycle 1) followed by single-agent panobinostat continual treatment phase(More)
2549 Background: Panobinostat (PAN), a hydroxamic acid derivative, is a potent pan-deacetylase inhibitor, demonstrating anti-tumor activities in a wide variety of preclinical models and showing promising clinical activity. This study elucidates the metabolic and elimination pathways of PAN using [14C]-PAN. METHODS Four patients with advanced cancer(More)
Bisphosphonates are potent inhibitors of bone resorption and provide a therapeutic benefit for patients with bone metastases. Zoledronic acid is a highly potent, nitrogen-containing bisphosphonate. In the present trial, we assessed the safety and tolerability of increasing doses of zoledronic acid and its effects on urinary markers of bone resorption in(More)