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Oncotarget. 2017 May 16;8(20):32918-32929. doi: 10.18632/oncotarget.16464.

A phase 2 study of vorinostat in locally advanced, recurrent, or metastatic adenoid cystic carcinoma.

Author information

1
Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA.
2
Mayo Clinic Arizona, Scottsdale, AZ, USA.
3
Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD, USA.
4
Current address: Stanford University, Palo Alto, CA, USA.
5
Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada.
6
Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, CA, USA.
7
Eugene Applebaum College of Pharmacy and Health Sciences, Physician Assistant Studies, Wayne State University, Detroit, MI, USA.
8
Current address: Yale Cancer Center, New Haven, CT, USA.

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.

KEYWORDS:

SAHA; adenoid cystic; salivary gland tumor; suberoylanilide hydroxamic acid; vorinostat

PMID:
28415633
PMCID:
PMC5464838
DOI:
10.18632/oncotarget.16464
[Indexed for MEDLINE]
Free PMC Article

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