RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Chemoprotective drugs, such as amifostine, may protect normal cells from the side effects of radiation therapy and chemotherapy. PURPOSE: Phase I/II trial to study the effectiveness of radiation therapy plus combination chemotherapy and amifostine in treating patients who have stage II, stage III, or stage IV head and neck cancer that cannot be surgically removed.

Condition	Treatment or Intervention	Phase
Nose Cancer Oral Cancer Throat Cancer Quality of Life	Drug: amifostine  Drug: cisplatin  Drug: fluorouracil  Drug: paclitaxel	Phase I Phase II

Further Study Details: 

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.

PROTOCOL 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.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically proven squamous cell carcinoma of the head and neck, including: Stage III or IV: oral cavity, paranasal sinus, hypopharynx, oropharynx, larynx, and nasopharynx OR Unknown primary carcinoma of the head and neck with greater than N1 disease if no planned neck dissection
• Evaluable disease
• No metastases below clavicle by clinical or radiographic diagnosis; All hypopharynx and nasopharynx patients with N3 disease undergo a CT scan of the chest

--Prior/Concurrent Therapy--

• Biologic therapy: Not specified
• Chemotherapy: No prior chemotherapy
• Endocrine therapy: Not specified
• Radiotherapy: No prior radiotherapy to the treatment field
• Surgery: Eligible for PEG gastrostomy
• Other: At least 24 hours since prior antihypertensive and diuretic medications (prior to amifostine and chemotherapy regimens)

--Patient Characteristics--

• Age: 18 and over
• Performance status: ECOG 0-2
• Life expectancy: Not specified
• Hematopoietic: Platelet count at least 130,000/mm3; WBC at least 3,400/mm3; Hemoglobin greater than 10.0 g/dL (transfusion allowed)
• Hepatic: Not specified
• Renal: Creatinine no greater than 1.4 mg/dL
• Cardiovascular: No active heart disease; No myocardial infarction within past 6 months; No uncontrolled congestive heart failure; No uncontrolled angina; Cardiac ejection fraction at least 50% by MUGA scan for patients under 65 without antecedent heart disease, at least 55% for patients over 65 and/or with antecedent heart disease
• Pulmonary: FEV greater than 60% of predicted
• Other: Not pregnant or nursing; Fertile patients must use effective contraception

Florida
      Sylvester Cancer Center, University of Miami, Miami,  Florida,  33136,  United States

Study chairs or principal investigators

Andre A. Abitbol,  Study Chair,  Sylvester Cancer Center   

Study ID Numbers:  CDR0000066650; SCCC-97098; NCI-V98-1474; ALZA-97-052-ii; BHM-98-32
Record last reviewed:  February 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003582
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08