Continuous infusion intravenous hydroxyurea plus concurrent hyperfractionated external radiation therapy for locally advanced squaraous cell cancers of the head and neck: less is better

Jonathan J. Bcitler, Richard V. Smith, Carl E. Silver, Randall Owen, Marvin P. Fried

Research output: Contribution to journalArticle

Abstract

Introduction: Oral hydroxyurea has been shown to be radiation sensitizer but has a short biologic half-life. Continuous infusion hydrox>oirea has the promise of producing a sustained cell cycle block in a radiosensitive phase. After performing a Phase I doseescalation study of continuous infusion hydroxyurea with concomitant, hyperfractionated external radiation for locally advanced squamous cell cancers of the Head and Neck(Beitler et al, Investigational New Drugs, 16:161-9,1998) we performed a Phase II study. Materials and Methods: Twenty-six patients with locally advanced, unresectable, squamous cell cancers of the head and neck were treated with 0.312 mg/m2 of continuous infusion hydroxyurea from Monday until Saturday. Patients received concurrent, hyperfractionated external radiation to deliver 74.4 Gy using 1.2 Gy BID fractions. Because of unacceptable late toxicities (Smith et al, Arch Otolaryngol Head Neck Surg, 126:384-9, 2000) the radiation was decreased to 60 Gy using 1.2 Gy BID fractions also accompanied by concurrent, continuous infusion hydroxyurea delivered throughout the shortened course of external radiation therapy. Sixteen patients were treated with the shortened schedule. Swallowing function was measured by dynamic swallowing studies using a computerized analysis, which we have previously described (Kotz T et al Arch Otol Head Neck Surg 125:410-413,1999). Results: The group receiving 74.4 Gy had a median follow-up of 26 months (range 5-73 months) and the group receiving 60 Gy had a median follow-up of 18 months (range 1-31 months). Overall Kaplan-Meier survival for the 74.4 Gy and 60 Gy groups was 73% versus 73% at 12 months and 54% versus 65% at 24 months (P = 0.56 by log-rank analysis). The shorter course of therapy produced significantly fewer long-term swallowing difficulties. Conclusion: As of this writing, decreasing the cumulative doses of both the external radiation and the continuous infusion hydroxyurea by 19% decreased toxicity while preserving survival.

Original languageEnglish (US)
Pages (from-to)516
Number of pages1
JournalCancer Journal
Volume9
Issue number6
StatePublished - 1996

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Hydroxyurea
Head and Neck Neoplasms
Intravenous Infusions
Radiotherapy
Deglutition
Radiation
Squamous Cell Neoplasms
Head
Investigational Drugs
Radiation-Sensitizing Agents
Survival
Half-Life
Appointments and Schedules
Cell Cycle

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

@article{2e11f162d82a4229946da73ec4c848e1,
title = "Continuous infusion intravenous hydroxyurea plus concurrent hyperfractionated external radiation therapy for locally advanced squaraous cell cancers of the head and neck: less is better",
abstract = "Introduction: Oral hydroxyurea has been shown to be radiation sensitizer but has a short biologic half-life. Continuous infusion hydrox>oirea has the promise of producing a sustained cell cycle block in a radiosensitive phase. After performing a Phase I doseescalation study of continuous infusion hydroxyurea with concomitant, hyperfractionated external radiation for locally advanced squamous cell cancers of the Head and Neck(Beitler et al, Investigational New Drugs, 16:161-9,1998) we performed a Phase II study. Materials and Methods: Twenty-six patients with locally advanced, unresectable, squamous cell cancers of the head and neck were treated with 0.312 mg/m2 of continuous infusion hydroxyurea from Monday until Saturday. Patients received concurrent, hyperfractionated external radiation to deliver 74.4 Gy using 1.2 Gy BID fractions. Because of unacceptable late toxicities (Smith et al, Arch Otolaryngol Head Neck Surg, 126:384-9, 2000) the radiation was decreased to 60 Gy using 1.2 Gy BID fractions also accompanied by concurrent, continuous infusion hydroxyurea delivered throughout the shortened course of external radiation therapy. Sixteen patients were treated with the shortened schedule. Swallowing function was measured by dynamic swallowing studies using a computerized analysis, which we have previously described (Kotz T et al Arch Otol Head Neck Surg 125:410-413,1999). Results: The group receiving 74.4 Gy had a median follow-up of 26 months (range 5-73 months) and the group receiving 60 Gy had a median follow-up of 18 months (range 1-31 months). Overall Kaplan-Meier survival for the 74.4 Gy and 60 Gy groups was 73{\%} versus 73{\%} at 12 months and 54{\%} versus 65{\%} at 24 months (P = 0.56 by log-rank analysis). The shorter course of therapy produced significantly fewer long-term swallowing difficulties. Conclusion: As of this writing, decreasing the cumulative doses of both the external radiation and the continuous infusion hydroxyurea by 19{\%} decreased toxicity while preserving survival.",
author = "Bcitler, {Jonathan J.} and Smith, {Richard V.} and Silver, {Carl E.} and Randall Owen and Fried, {Marvin P.}",
year = "1996",
language = "English (US)",
volume = "9",
pages = "516",
journal = "Cancer Journal from Scientific American",
issn = "1528-9117",
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TY - JOUR

T1 - Continuous infusion intravenous hydroxyurea plus concurrent hyperfractionated external radiation therapy for locally advanced squaraous cell cancers of the head and neck

T2 - less is better

AU - Bcitler, Jonathan J.

AU - Smith, Richard V.

AU - Silver, Carl E.

AU - Owen, Randall

AU - Fried, Marvin P.

PY - 1996

Y1 - 1996

N2 - Introduction: Oral hydroxyurea has been shown to be radiation sensitizer but has a short biologic half-life. Continuous infusion hydrox>oirea has the promise of producing a sustained cell cycle block in a radiosensitive phase. After performing a Phase I doseescalation study of continuous infusion hydroxyurea with concomitant, hyperfractionated external radiation for locally advanced squamous cell cancers of the Head and Neck(Beitler et al, Investigational New Drugs, 16:161-9,1998) we performed a Phase II study. Materials and Methods: Twenty-six patients with locally advanced, unresectable, squamous cell cancers of the head and neck were treated with 0.312 mg/m2 of continuous infusion hydroxyurea from Monday until Saturday. Patients received concurrent, hyperfractionated external radiation to deliver 74.4 Gy using 1.2 Gy BID fractions. Because of unacceptable late toxicities (Smith et al, Arch Otolaryngol Head Neck Surg, 126:384-9, 2000) the radiation was decreased to 60 Gy using 1.2 Gy BID fractions also accompanied by concurrent, continuous infusion hydroxyurea delivered throughout the shortened course of external radiation therapy. Sixteen patients were treated with the shortened schedule. Swallowing function was measured by dynamic swallowing studies using a computerized analysis, which we have previously described (Kotz T et al Arch Otol Head Neck Surg 125:410-413,1999). Results: The group receiving 74.4 Gy had a median follow-up of 26 months (range 5-73 months) and the group receiving 60 Gy had a median follow-up of 18 months (range 1-31 months). Overall Kaplan-Meier survival for the 74.4 Gy and 60 Gy groups was 73% versus 73% at 12 months and 54% versus 65% at 24 months (P = 0.56 by log-rank analysis). The shorter course of therapy produced significantly fewer long-term swallowing difficulties. Conclusion: As of this writing, decreasing the cumulative doses of both the external radiation and the continuous infusion hydroxyurea by 19% decreased toxicity while preserving survival.

AB - Introduction: Oral hydroxyurea has been shown to be radiation sensitizer but has a short biologic half-life. Continuous infusion hydrox>oirea has the promise of producing a sustained cell cycle block in a radiosensitive phase. After performing a Phase I doseescalation study of continuous infusion hydroxyurea with concomitant, hyperfractionated external radiation for locally advanced squamous cell cancers of the Head and Neck(Beitler et al, Investigational New Drugs, 16:161-9,1998) we performed a Phase II study. Materials and Methods: Twenty-six patients with locally advanced, unresectable, squamous cell cancers of the head and neck were treated with 0.312 mg/m2 of continuous infusion hydroxyurea from Monday until Saturday. Patients received concurrent, hyperfractionated external radiation to deliver 74.4 Gy using 1.2 Gy BID fractions. Because of unacceptable late toxicities (Smith et al, Arch Otolaryngol Head Neck Surg, 126:384-9, 2000) the radiation was decreased to 60 Gy using 1.2 Gy BID fractions also accompanied by concurrent, continuous infusion hydroxyurea delivered throughout the shortened course of external radiation therapy. Sixteen patients were treated with the shortened schedule. Swallowing function was measured by dynamic swallowing studies using a computerized analysis, which we have previously described (Kotz T et al Arch Otol Head Neck Surg 125:410-413,1999). Results: The group receiving 74.4 Gy had a median follow-up of 26 months (range 5-73 months) and the group receiving 60 Gy had a median follow-up of 18 months (range 1-31 months). Overall Kaplan-Meier survival for the 74.4 Gy and 60 Gy groups was 73% versus 73% at 12 months and 54% versus 65% at 24 months (P = 0.56 by log-rank analysis). The shorter course of therapy produced significantly fewer long-term swallowing difficulties. Conclusion: As of this writing, decreasing the cumulative doses of both the external radiation and the continuous infusion hydroxyurea by 19% decreased toxicity while preserving survival.

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