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 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)18-25
Number of pages8
JournalHead and Neck
Volume29
Issue number1
DOIs
StatePublished - Jan 2007

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Ribonucleosides
Phase II Clinical Trials
Hydroxyurea
Oxidoreductases
Radiotherapy
Radiation
Hypopharynx
Oropharynx
Survival
Deglutition Disorders
Platinum
Cisplatin
Mouth
Carcinoma, squamous cell of head and neck
Squamous Cell Carcinoma
Appointments and Schedules
Cell Cycle
Neck
Pharmacokinetics
Head

Keywords

  • Cell cycle blockade
  • Concurrent chemoradiation
  • Hydroxyurea
  • Radiosensitizer

ASJC Scopus subject areas

  • Otorhinolaryngology

Cite this

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title = "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",
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.",
keywords = "Cell cycle blockade, Concurrent chemoradiation, Hydroxyurea, Radiosensitizer",
author = "Beitler, {Jonathan J.} and Smith, {Richard V.} and Owen, {Randall P.} and Silver, {Carl E.} and Madhu Mazumdar and Scott Wadler",
year = "2007",
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TY - JOUR

T1 - 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

T2 - Toxicity and efficacy with continuous ribonucleoside reductase inhibition

AU - Beitler, Jonathan J.

AU - Smith, Richard V.

AU - Owen, Randall P.

AU - Silver, Carl E.

AU - Mazumdar, Madhu

AU - Wadler, Scott

PY - 2007/1

Y1 - 2007/1

N2 - 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.

AB - 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.

KW - Cell cycle blockade

KW - Concurrent chemoradiation

KW - Hydroxyurea

KW - Radiosensitizer

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