Vorinostat (V) Intratumoral Levels And Biomarker Response In A Window Of Opportunity Trial In Patients With Resectable Aerodigestive Tract Cancer.
JOURNAL OF CLINICAL ONCOLOGY(2012)
摘要
7022 Background: Aerodigestive tract cancer (ADT) is the leading cause of cancer-related death in the US. New effective treatments are needed. Among a panel of drugs causing growth inhibition of lung cancer cells and repression of cyclin D1, the histone deacetylase inhibitor V was found most potent. To translate studies into the clinic, a window of opportunity trial of V was conducted. Methods: Pts with resectable ADT received 400 mg V once daily orally for 7 days prior to surgical resection. Serum samples were obtained before the last V dose and at the time of biopsy. Tumor tissue was immediately snap-frozen in liquid nitrogen, stored at -70°C, homogenized in three parts PBS (1:3g/v). V was quantitated with a LC-MS/MS assay. Post- versus pre-treatment tumor biopsies were scored for necrosis, acute and chronic inflammation, and immunohistochemical changes in Ki-67, cyclin E, cyclin D1, EGFR, phospho-EGFR, p21, p27 and caspase. Results: 15 pts enrolled, 9 pts took V for a median of 7 days (3-9), underwent ...
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