Paclitaxel and Radiation Therapy Plus Chemoprotection With Amifostine in Treating Patients With Stage III or Stage IV Head and Neck Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Chemoprotective drugs, such as amifostine, may protect normal cells from the side effects of chemotherapy. PURPOSE: Phase I/II trial to study the effectiveness of paclitaxel and radiation therapy plus chemoprotection with amifostine in treating patients with stage III or stage IV head and neck cancer.

Detailed Description
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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.

Official Title
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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

Conditions
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Head and Neck Cancer, Oral Complications

Intervention / Treatment
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* Drug: amifostine trihydrate
* Drug: paclitaxel
* Procedure: conventional surgery
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed stage III or IV squamous cell head and neck cancer T3-4, N0-3, M0 PATIENT CHARACTERISTICS: Age: 18 and over Performance Status: ECOG 0-2 Life Expectancy: Not specified Hematopoietic: WBC at least 2,000/mm^3 Platelet count at least 50,000/mm^3 Hepatic: Bilirubin no greater than 3.0 mg/dL SGOT no greater than 3 times upper limit of normal Renal: Creatinine no greater than 3.0 mg/dL Other: Not pregnant or nursing PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: Not specified Endocrine therapy: Not specified Radiotherapy: Not specified Surgery: Not specified Other: No concurrent beta-adrenergic blocking agents

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Paclitaxel, amifostine, RT<br>Dose-escalation arm for paclitaxel with amifostine and RT. | Drug: amifostine trihydrate<br> <br> Drug: paclitaxel<br> <br> Procedure: conventional surgery<br> <br> Radiation: radiation therapy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety | Safety is evaluated in this dose-escalation study | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate | Response in terms of CR, PR, stable disease, or progression was determined | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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oral complications, stage III squamous cell carcinoma of the lip and oral cavity, stage IV squamous cell carcinoma of the lip and oral cavity, stage III squamous cell carcinoma of the oropharynx, stage IV squamous cell carcinoma of the oropharynx, stage III squamous cell carcinoma of the nasopharynx, stage IV squamous cell carcinoma of the nasopharynx, stage III squamous cell carcinoma of the hypopharynx, stage IV squamous cell carcinoma of the hypopharynx, stage III squamous cell carcinoma of the larynx, stage IV squamous cell carcinoma of the larynx, stage III squamous cell carcinoma of the paranasal sinus and nasal cavity, stage IV squamous cell carcinoma of the paranasal sinus and nasal cavity