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

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

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.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Adenoid Cystic / drug therapy*
  • Carcinoma, Adenoid Cystic / genetics
  • Chromatin Assembly and Disassembly
  • Female
  • Gene Regulatory Networks
  • Histone Deacetylase Inhibitors / administration & dosage*
  • Histone Deacetylase Inhibitors / adverse effects
  • Humans
  • Hydroxamic Acids / administration & dosage*
  • Hydroxamic Acids / adverse effects
  • Male
  • Middle Aged
  • Mutation
  • Neoplasm Metastasis
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / genetics
  • Pharmacogenomic Variants
  • Salivary Gland Neoplasms / drug therapy*
  • Salivary Gland Neoplasms / genetics
  • Vorinostat
  • Whole Exome Sequencing
  • Young Adult

Substances

  • Histone Deacetylase Inhibitors
  • Hydroxamic Acids
  • Vorinostat