Trial Information

Phase I/II Study to Evaluate Combined Hyperfractionated Radiation Therapy and 5-Fluorouracil, Cisplatin and Paclitaxel (Taxol) and Amifostine (WR 2721, Ethyol) in Stage III and IV Inoperable Head and Neck Carcinomas

OBJECTIVES: I. Assess the impact of amifostine on the acute tolerance of combined
hyperfractionated radiation therapy and fluorouracil, cisplatin, and paclitaxel with
amifostine, in terms of the grade and duration of acute mucositis and dermatitis, and acute
hematologic tolerance in patients with stage III or IV unresectable head and neck carcinoma.
II. Determine the local control and survival associated with this regimen in these patients.
III. Determine the long term chronic toxic effects of this regimen in terms of swallowing
dysfunction, PEG dependency, and xerostomia in these patients. IV. Determine the quality of
life post therapy by assessment of speech and swallowing function in these patients. V.
Determine if radiation dose escalation in patients with treatment interruption achieve an
isoeffect on locoregional control. VI. Determine the safe optimal dose of paclitaxel to be
combined with hyperfractionated radiation therapy, fluorouracil, cisplatin, and amifostine
in these patients. VII. Determine the correlation of p53 chromosome expression on
locoregional control and survival of these patients. VIII. Quantitate tumor volumetrics and
correlate with stage, resectability status, and locoregional control and survival of these
patients.

OUTLINE: This is a dose escalation of paclitaxel, multicenter study. Patients are stratified
by performance status, stage, institution, tumor volumetrics, resectability, and p53
expression. Patients receive amifostine IV over 10 minutes on Monday of weeks 1, 5, and 9,
and over 5-7 minutes Tuesday through Friday of weeks 1, 5, and 9 and Monday through Friday
of weeks 2, 3, 4, 6, and 7. Within 10-15 minutes of amifostine administration, patients
receive paclitaxel IV over 3 hours, cisplatin IV over 2 hours on days 1, 29, and 56, and
fluorouracil IV over 72 hours on days 1-4, 29-33, and 56-60. Starting on day 2, patients
receive hyperfractionated external beam radiotherapy twice daily over 6.5 weeks, following
amifostine IV over 5-7 minutes Monday through Friday. Cohorts of 6-20 patients each receive
escalating doses of paclitaxel. Quality of life is assessed. Patients are followed monthly
for 1 year, every 2 months for 1 year, every 6 months for 3 years, and then annually
thereafter until death.

PROJECTED ACCRUAL: A minimum of 36 patients will be accrued for this study within 20 months.