1. A phase 2 study of vorinostat in locally advanced, recurrent, or metastatic adenoid cystic carcinoma
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Scott A. Boerner, Ammar Sukari, Lance K. Heilbrun, Aaron R. Hansen, Joseph Chao, Daryn Smith, Smriti Malasi, Mary Jo Pilat, Alice P. Chen, Michael T. Barrett, Priscila H. Goncalves, Elizabeth Lenkiewicz, Shivaani Kummar, Richard Piekarz, Lindsay Casetta, Patricia LoRusso, and Lillian L. Siu more...
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Adult ,Male ,0301 basic medicine ,Oncology ,Pathology ,medicine.medical_specialty ,Pharmacogenomic Variants ,Adenoid cystic carcinoma ,adenoid cystic ,Phases of clinical research ,Hydroxamic Acids ,Adenoid ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Exome Sequencing ,medicine ,Humans ,Gene Regulatory Networks ,Neoplasm Metastasis ,Adverse effect ,Vorinostat ,Aged ,Hematology ,business.industry ,SAHA ,Cancer ,salivary gland tumor ,Middle Aged ,Chromatin Assembly and Disassembly ,Salivary Gland Neoplasms ,medicine.disease ,Carcinoma, Adenoid Cystic ,suberoylanilide hydroxamic acid ,3. Good health ,Histone Deacetylase Inhibitors ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Mutation ,Female ,Neoplasm Recurrence, Local ,business ,Research Paper ,medicine.drug ,Biomedical sciences - Abstract
// Priscila H. Goncalves 1 , Lance K. Heilbrun 1 , Michael T. Barrett 2 , Shivaani Kummar 4, 8 , Aaron R. Hansen 3 , Lillian L. Siu 3 , Richard L. Piekarz 4 , Ammar W. Sukari 1 , Joseph Chao 5 , Mary Jo Pilat 1, 6 , Daryn W. Smith 1 , Lindsay Casetta 1 , Scott A. Boerner 1, 7 , Alice Chen 4 , Elizabeth Lenkiewicz 2 , Smriti Malasi 2 , Patricia M. LoRusso 1, 7 1 Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA 2 Mayo Clinic Arizona, Scottsdale, AZ, USA 3 Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada 4 Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD, USA 5 Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, CA, USA 6 Eugene Applebaum College of Pharmacy and Health Sciences, Physician Assistant Studies, Wayne State University, Detroit, MI, USA 7 Current address: Yale Cancer Center, New Haven, CT, USA 8 Current address: Stanford University, Palo Alto, CA, USA Correspondence to: Priscila H. Goncalves, email: priscila.goncalves@nih.gov Keywords: adenoid cystic, salivary gland tumor, vorinostat, suberoylanilide hydroxamic acid, SAHA Received: February 09, 2017 Accepted: March 14, 2017 Published: March 22, 2017 ABSTRACT Purpose: Vorinostat is a histone deacetylase inhibitor (HDACi). Based on a confirmed partial response (PR) in an adenoid cystic carcinoma (ACC) patient treated with vorinostat in a prior phase 1 trial, we initiated this phase 2 trial. Methods: Vorinostat was administered orally 400 mg daily, 28 day cycles. The primary objective was to evaluate response rate (RR). Exploratory studies included whole exome sequencing (WES) of selected patients. Results: Thirty patients were enrolled. Median age of patients was 53 years (range 21–73). Median number of cycles was 5 (range 1-66). Lymphopenia ( n = 5), hypertension ( n = 3), oral pain ( n = 2), thromboembolic events ( n = 2) and fatigue ( n = 2) were the only grade 3 adverse events (AEs) that occurred in more than 1 patient. Eleven patients were dose reduced secondary to drug-related AEs. Two patients had a partial response (PR), with response durations of 53 and 7.2 months. One patient had a minor response with a decrease in ascites (for 19 cycles). Stable disease was the best response in 27 patients. Targeted and WES of 8 patients in this trial identified mutations in chromatin remodeling genes highlighting the role of the epigenome in ACC. Conclusion: Vorinostat demonstrated efficacy in patients with ACC supporting the inclusion of HDACi in future studies to treat ACC. more...
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- 2017
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