Trial Information

Phase I/II Study of Escalating Doses of Taxol Used Concurrently With Ethyol and Accelerated Hyperfractionated Radiotherapy in the Treatment of Stage III and IV Carcinoma of the Head and Neck

OBJECTIVES:

- Determine the maximum tolerated dose of paclitaxel with amifostine and radiotherapy in
patients with stage III or IV head and neck cancer.

- Determine the toxic effects and complications of this regimen in terms of mucositis
reduction in these patients.

- Determine the complete response rate and progression-free survival of patients treated
with this regimen.

- Determine whether amifostine modulates the plasma pharmacokinetics of paclitaxel in
these patients.

OUTLINE: This is a dose-escalation study of paclitaxel with and without amifostine.

Patients receive paclitaxel IV on days 1, 8, 15, 29, 36, and 43 for a total of 3-6 doses.
Patients also undergo radiotherapy twice daily for 6 weeks, except for days when paclitaxel
is given.

Cohorts of 2-5 patients receive escalating doses of paclitaxel until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose at which 2-3 patients experience
dose-limiting toxicity. An additional 10 patients are treated at the MTD.

After determination of the MTD for paclitaxel, subsequent patients also receive amifostine
IV over 15 minutes on days 1, 8, 29, and 36 and radiotherapy on days 2-5 and 30-33.
Determination of the MTD for this drug combination is carried out as with paclitaxel alone.

At 4 to 8 weeks after the last treatment of radiotherapy, patients undergo CT scanning to
determine response. Patients with residual masses undergo neck dissection. Patients with
complete or partial response at the primary site are followed without surgery.

Patients are followed every 6 months.

PROJECTED ACCRUAL: A maximum of 37 patients will be accrued for this study.