A phase 2 study of vorinostat in locally advanced, recurrent, or metastatic adenoid cystic carcinoma.
Oncotarget
; 8(20): 32918-32929, 2017 May 16.
Article
em En
| MEDLINE
| ID: mdl-28415633
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.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias das Glândulas Salivares
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Carcinoma Adenoide Cístico
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Inibidores de Histona Desacetilases
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Ácidos Hidroxâmicos
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Recidiva Local de Neoplasia
Limite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Oncotarget
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Estados Unidos