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

Priscila H. Goncalves, Lance K. Heilbrun, Michael T. Barrett, Shivaani Kummar, Aaron R. Hansen, Lillian L. Siu, Richard L. Piekarz, Ammar W. Sukari, Joseph Chao, Mary Jo Pilat, Daryn W. Smith, Lindsay Casetta, Scott A. Boerner, Alice Chen, Elizabeth Lenkiewicz, Smriti Malasi, Patricia M. LoRusso

Research output: Contribution to journalArticle

14 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)32918-32929
Number of pages12
JournalOncotarget
Volume8
Issue number20
DOIs
StatePublished - 2017

Keywords

  • Adenoid cystic
  • SAHA
  • Salivary gland tumor
  • Suberoylanilide hydroxamic acid
  • Vorinostat

ASJC Scopus subject areas

  • Oncology

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    Goncalves, P. H., Heilbrun, L. K., Barrett, M. T., Kummar, S., Hansen, A. R., Siu, L. L., Piekarz, R. L., Sukari, A. W., Chao, J., Pilat, M. J., Smith, D. W., Casetta, L., Boerner, S. A., Chen, A., Lenkiewicz, E., Malasi, S., & LoRusso, P. M. (2017). A phase 2 study of vorinostat in locally advanced, recurrent, or metastatic adenoid cystic carcinoma. Oncotarget, 8(20), 32918-32929. https://doi.org/10.18632/oncotarget.16464