A phase 1 trial of Vorinostat in combination with concurrent chemoradiation therapy in the treatment of advanced staged head and neck squamous cell carcinoma.
Anemia
/ chemically induced
Antineoplastic Agents
/ administration & dosage
Chemoradiotherapy
/ adverse effects
Cisplatin
/ administration & dosage
Drug Eruptions
Female
Head and Neck Neoplasms
/ therapy
Humans
Leukopenia
/ chemically induced
Male
Maximum Tolerated Dose
Middle Aged
Mucositis
/ chemically induced
Squamous Cell Carcinoma of Head and Neck
/ therapy
Survival Analysis
Treatment Outcome
Vorinostat
/ administration & dosage
Weight Loss
Chemoradiation therapy
HPV-related head and neck cancer
Head and neck cancer
Histone deacetylase inhibitors in head and neck cancer
Organ preservation
Oropharyngeal cancer
Phase I trial in advance stage head and neck cancer
Journal
Investigational new drugs
ISSN: 1573-0646
Titre abrégé: Invest New Drugs
Pays: United States
ID NLM: 8309330
Informations de publication
Date de publication:
08 2019
08 2019
Historique:
received:
04
06
2018
accepted:
12
11
2018
pubmed:
21
12
2018
medline:
7
2
2020
entrez:
21
12
2018
Statut:
ppublish
Résumé
Purpose Vorinostat is a potent HDAC inhibitor that sensitizes head and neck squamous cell carcinoma (HNSCC) to cytotoxic therapy while sparing normal epithelium. The primary objective of this Phase I study was to determine the maximally tolerated dose (MTD) and safety of Vorinostat in combination with standard chemoradiation therapy treatment in HNSCC. Patients and Methods Eligible patients had pathologically confirmed Stage III, IVa, IVb HNSCC, that was unresectable or borderline resectable involving the larynx, hypopharynx, nasopharynx, and oropharynx. Vorinostat was administered at the assigned dosage level (100-400 mg, three times weekly) in a standard 3 + 3 dose escalation design. Vorinostat therapy began 1 week prior to initiation of standard, concurrent chemoradiation therapy and continued during the entire course of therapy. Results Twenty six patients met eligibility criteria and completed the entire protocol. The primary tumor sites included tonsil (12), base of tongue (9), posterior pharyngeal wall (1), larynx (4) and hypopharynx (3). Of the 26 patients, 17 were HPV-positive and 9 were HPV-negative. The MTD of Vorinostat was 300 mg administered every other day. Anemia (n = 23/26) and leukopenia (n = 20/26) were the most commonly identified toxicities. The most common Grade3/4 events included leukopenia (n = 11) and lymphopenia (n = 17). No patient had Grade IV mucositis, dermatitis or xerostomia. The median follow time was 33.8 months (range 1.6-82.9 months). Twenty four of 26 (96.2%) patients had a complete response to therapy. Conclusion Vorinostat in combination with concurrent chemoradiation therapy is a safe and highly effective treatment regimen in HNSCC. There was a high rate of complete response to therapy with toxicity rates comparable, if not favorable to existing therapies. Further investigation in Phase II and III trials is strongly recommended.
Identifiants
pubmed: 30569244
doi: 10.1007/s10637-018-0696-4
pii: 10.1007/s10637-018-0696-4
doi:
Substances chimiques
Antineoplastic Agents
0
Vorinostat
58IFB293JI
Cisplatin
Q20Q21Q62J
Types de publication
Clinical Trial, Phase I
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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