Oncotarget

Research Papers:

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 and Patricia M. LoRusso

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Oncotarget. 2017; 8:32918-32929. https://doi.org/10.18632/oncotarget.16464

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Abstract

Priscila H. Goncalves1, Lance K. Heilbrun1, Michael T. Barrett2, Shivaani Kummar4,8, Aaron R. Hansen3, Lillian L. Siu3, Richard L. Piekarz4, Ammar W. Sukari1, Joseph Chao5, Mary Jo Pilat1,6, Daryn W. Smith1, Lindsay Casetta1, Scott A. Boerner1,7, Alice Chen4, Elizabeth Lenkiewicz2, Smriti Malasi2, Patricia M. LoRusso1,7

1Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA

2Mayo Clinic Arizona, Scottsdale, AZ, USA

3Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada

4Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD, USA

5Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, CA, USA

6Eugene Applebaum College of Pharmacy and Health Sciences, Physician Assistant Studies, Wayne State University, Detroit, MI, USA

7Current address: Yale Cancer Center, New Haven, CT, USA

8Current 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.


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