PMID- 28415633 OWN - NLM STAT- MEDLINE DCOM- 20180313 LR - 20221207 IS - 1949-2553 (Electronic) IS - 1949-2553 (Linking) VI - 8 IP - 20 DP - 2017 May 16 TI - A phase 2 study of vorinostat in locally advanced, recurrent, or metastatic adenoid cystic carcinoma. PG - 32918-32929 LID - 10.18632/oncotarget.16464 [doi] AB - 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. FAU - Goncalves, Priscila H AU - Goncalves PH AD - Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA. FAU - Heilbrun, Lance K AU - Heilbrun LK AD - Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA. FAU - Barrett, Michael T AU - Barrett MT AD - Mayo Clinic Arizona, Scottsdale, AZ, USA. FAU - Kummar, Shivaani AU - Kummar S AD - Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD, USA. AD - Current address: Stanford University, Palo Alto, CA, USA. FAU - Hansen, Aaron R AU - Hansen AR AD - Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada. FAU - Siu, Lillian L AU - Siu LL AD - Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada. FAU - Piekarz, Richard L AU - Piekarz RL AD - Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD, USA. FAU - Sukari, Ammar W AU - Sukari AW AD - Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA. FAU - Chao, Joseph AU - Chao J AD - Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, CA, USA. FAU - Pilat, Mary Jo AU - Pilat MJ AD - Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA. AD - Eugene Applebaum College of Pharmacy and Health Sciences, Physician Assistant Studies, Wayne State University, Detroit, MI, USA. FAU - Smith, Daryn W AU - Smith DW AD - Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA. FAU - Casetta, Lindsay AU - Casetta L AD - Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA. FAU - Boerner, Scott A AU - Boerner SA AD - Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA. AD - Current address: Yale Cancer Center, New Haven, CT, USA. FAU - Chen, Alice AU - Chen A AD - Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD, USA. FAU - Lenkiewicz, Elizabeth AU - Lenkiewicz E AD - Mayo Clinic Arizona, Scottsdale, AZ, USA. FAU - Malasi, Smriti AU - Malasi S AD - Mayo Clinic Arizona, Scottsdale, AZ, USA. FAU - LoRusso, Patricia M AU - LoRusso PM AD - Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA. AD - Current address: Yale Cancer Center, New Haven, CT, USA. LA - eng GR - U01 CA062487/CA/NCI NIH HHS/United States GR - UL1 TR001863/TR/NCATS NIH HHS/United States GR - P30 CA022453/CA/NCI NIH HHS/United States GR - UM1 CA186717/CA/NCI NIH HHS/United States GR - U01 CA132123/CA/NCI NIH HHS/United States GR - UM1 CA186689/CA/NCI NIH HHS/United States PT - Clinical Trial, Phase II PT - Journal Article PL - United States TA - Oncotarget JT - Oncotarget JID - 101532965 RN - 0 (Histone Deacetylase Inhibitors) RN - 0 (Hydroxamic Acids) RN - 58IFB293JI (Vorinostat) SB - IM MH - Adult MH - Aged MH - Carcinoma, Adenoid Cystic/*drug therapy/genetics MH - Chromatin Assembly and Disassembly MH - Female MH - Gene Regulatory Networks MH - Histone Deacetylase Inhibitors/*administration & dosage/adverse effects MH - Humans MH - Hydroxamic Acids/*administration & dosage/adverse effects MH - Male MH - Middle Aged MH - Mutation MH - Neoplasm Metastasis MH - Neoplasm Recurrence, Local/*drug therapy/genetics MH - Pharmacogenomic Variants MH - Salivary Gland Neoplasms/*drug therapy/genetics MH - Vorinostat MH - Exome Sequencing MH - Young Adult PMC - PMC5464838 OTO - NOTNLM OT - SAHA OT - adenoid cystic OT - salivary gland tumor OT - suberoylanilide hydroxamic acid OT - vorinostat COIS- CONFLICTS OF INTEREST All authors except LS and JC have no conflicts of interest. LS has research funding (for clinical trials) from Merck and is on Merck advisory board. JC has research funding (institutional for clinical trials) from Merck. EDAT- 2017/04/19 06:00 MHDA- 2018/03/14 06:00 PMCR- 2017/05/16 CRDT- 2017/04/19 06:00 PHST- 2017/02/09 00:00 [received] PHST- 2017/03/14 00:00 [accepted] PHST- 2017/04/19 06:00 [pubmed] PHST- 2018/03/14 06:00 [medline] PHST- 2017/04/19 06:00 [entrez] PHST- 2017/05/16 00:00 [pmc-release] AID - 16464 [pii] AID - 10.18632/oncotarget.16464 [doi] PST - ppublish SO - Oncotarget. 2017 May 16;8(20):32918-32929. doi: 10.18632/oncotarget.16464.