Investigational New Drugs

, Volume 37, Issue 4, pp 702–710 | Cite as

A phase 1 trial of Vorinostat in combination with concurrent chemoradiation therapy in the treatment of advanced staged head and neck squamous cell carcinoma

  • Theodoros N. TeknosEmail author
  • J. Grecula
  • A. Agrawal
  • M. O. Old
  • E. Ozer
  • R. Carrau
  • S. Kang
  • J. Rocco
  • D. Blakaj
  • V. Diavolitsis
  • B. Kumar
  • P. Kumar
  • Q. Pan
  • M. Palettas
  • L. Wei
  • R. Baiocchi
  • P. Savvides


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.


Head and neck cancer Oropharyngeal cancer Chemoradiation therapy Organ preservation Phase I trial in advance stage head and neck cancer Histone deacetylase inhibitors in head and neck cancer HPV-related head and neck cancer 



This study was approved and funded by the National Comprehensive Cancer Network (NCCN) Oncology Research Program from general research support provided by Merck & Co., Inc.


This study was funded by the National Comprehensive Cancer Network (NCCN) Oncology Research Program from general research support provided by Merck & Co., Inc.

Compliance and ethical standards

Conflict of interest

All authors declare that there are no conflicts of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.


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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Theodoros N. Teknos
    • 1
    • 2
    Email author
  • J. Grecula
    • 3
  • A. Agrawal
    • 1
  • M. O. Old
    • 1
  • E. Ozer
    • 1
  • R. Carrau
    • 1
  • S. Kang
    • 1
  • J. Rocco
    • 1
  • D. Blakaj
    • 3
  • V. Diavolitsis
    • 3
  • B. Kumar
    • 1
  • P. Kumar
    • 1
  • Q. Pan
    • 1
  • M. Palettas
    • 4
  • L. Wei
    • 4
  • R. Baiocchi
    • 5
  • P. Savvides
    • 5
  1. 1.OtolaryngologyThe Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James)ColumbusUSA
  2. 2.Seidman Cancer CenterUniversity Hospitals Cleveland Medical CenterClevelandUSA
  3. 3.Radiation OncologyThe Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James)ColumbusUSA
  4. 4.Center for BiostatisticsThe Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James)ColumbusUSA
  5. 5.Hematology-Medical OncologyThe Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James)ColumbusUSA

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