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

Jonathan J. Beitler, Richard V. Smith, Randall P. Owen, Carl E. Silver, Madhu Mazumdar, Scott Wadler

Research output: Contribution to journalArticle

7 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)18-25
Number of pages8
JournalHead and Neck
Issue number1
StatePublished - Jan 1 2007



  • Cell cycle blockade
  • Concurrent chemoradiation
  • Hydroxyurea
  • Radiosensitizer

ASJC Scopus subject areas

  • Otorhinolaryngology

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