Phase II clinical trial of parenteral hydroxyurea and hyperfractionated, accelerated external beam radiation therapy in patients with advanced squamous cell carcinoma of the head and neck: Toxicity and efficacy with continuous ribonucleoside reductase inhibition

Authors

  • Jonathan J. Beitler MD, MBA, FACR,

    Corresponding author
    1. Department of Radiation Oncology, Montefiore Medical Center and the Albert EinsteinCollege of Medicine, Bronx, New York
    2. Department of Otolaryngology, Montefiore Medical Center and the Albert EinsteinCollege of Medicine, Bronx, New York
    • Department of Radiation Oncology, Montefiore Medical Center and the Albert EinsteinCollege of Medicine, Bronx, New York
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  • Richard V. Smith MD,

    1. Department of Otolaryngology, Montefiore Medical Center and the Albert EinsteinCollege of Medicine, Bronx, New York
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  • Randall P. Owen MD, MS,

    1. Department of Surgery, Montefiore Medical Center and the Albert EinsteinCollege of Medicine, Bronx, New York
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  • Carl E. Silver MD,

    1. Department of Surgery, Montefiore Medical Center and the Albert EinsteinCollege of Medicine, Bronx, New York
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  • Madhu Mazumdar PhD,

    1. Department of Public Health and the Division of Biostatistics and Epidemiology,Weill Medical College of Cornell University, NY, New York
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  • Scott Wadler MD

    1. Department of Medical Oncology, Montefiore Medical Center and theAlbert Einstein College of Medicine, Bronx, New York
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  • Reprints are not available.

  • Meeting Presentations at American Radium Society-2003, First International Conference on Translational Research and Pre-Clinical Strategies in Radio-Oncology-2000, American Head and Neck Society-1999.

Abstract

Background

Almost all concurrent chemoradiation regimens for head and neck are platinum based; however, cisplatin is associated with severe renal, oto-, and neurotoxicity. Hydroxyurea (HU) has been associated with fewer irreversible toxicities. We obtained HU in parenteral form to be administered continually during the radiation treatment. Intravenous HU promised better pharmacokinetics and cell cycle blockade.

Methods

Participants had biopsy-proven, untreated squamous cell carcinoma of the oral cavity, oropharynx (stage IV) and hypopharynx (stages II–IV). Radiation therapy consisted initially of 74.4 Gy administered in twice daily 1.2-Gy fractions. After 20 patients, the radiation dose was reduced to 60.0 Gy, and another 16 patients were enrolled.

Results

Patients received HU by Continuous Ambulatory Drug Delivery (CADD) pump on a daily ×5 schedule during radiation therapy. Because of persistent long-term dysphagia, after 20 patients, the dose of external beam radiation therapy was reduced from 74 to 60 Gy, and the duration of concurrent HU was correspondingly reduced. The new regimen was much better tolerated. The median survival for the group as a whole was 30 months. Within this small study, there were no significant differences in survival, regional control, or local control between the 2 groups.

Conclusions

Lower doses of concurrent parenteral HU and hyperfractionated radiation therapy are tolerable and promising. © 2006 Wiley Periodicals, Inc. Head Neck, 2006

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