RATIONALE: Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining chemotherapy with radiation therapy may kill more tumor cells. Amifostine may protect normal cells from the side effects of chemotherapy and radiation therapy.

PURPOSE: Randomized phase II trial to compare the effectiveness of radiation therapy combined with carboplatin and paclitaxel with or without amifostine in treating patients who have newly diagnosed stage II, stage III, or stage IV head and neck cancer.

Condition	Treatment or Intervention	Phase
Drug Toxicity Head and Neck Cancer oral complications of chemotherapy and head and neck radiation radiation toxicity	Drug: amifostine  Drug: carboplatin  Drug: paclitaxel  Procedure: chemoprotection  Procedure: chemotherapy  Procedure: complications of therapy assessment/management  Procedure: radiation therapy  Procedure: radioprotection  Procedure: supportive care/therapy	Phase II

Further Study Details: 

OBJECTIVES: Primary

• Compare the 1-year rate of local and regional disease control in patients with newly diagnosed stage II, III, or IV squamous cell carcinoma of the head and neck treated with concurrent radiotherapy and chemotherapy comprising carboplatin and paclitaxel with vs without amifostine.
• Compare the 3- and 6-month incidence of grade 2 or 3 chronic xerostomia in patients treated with these regimens.
• Compare the incidence of grade 3 and 4 mucositis after radiotherapy in patients treated with these regimens.
• Compare the median duration of dependence on percutaneous endoscopic gastrectomy (PEG) for adequate nutrition in patients treated with these regimens.

Secondary

• Compare the duration of grade 3 and 4 mucositis in patients treated with these regimens.
• Compare the 3-, 6-, and 12-month dependence on PEG in patients treated with these regimens.
• Compare time to disease progression in patients treated with these regimens.
• Compare quality of life of patients treated with these regimens.
• Compare 2-year local and regional disease control in patients treated with these regimens.
• Compare 2-year survival of patients treated with these regimens.

OUTLINE: This is a randomized study. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive carboplatin and paclitaxel once weekly for 6 weeks. Patients also undergo radiotherapy, concurrently with chemotherapy, once daily for 4 weeks and then twice daily for 2 weeks.
• Arm II: Patients receive chemoradiotherapy as in arm I. Patients also receive amifostine subcutaneously once daily. Quality of life is assessed at baseline and then at 8, 12, 24, and 52 weeks after completion of study therapy.

Patients are followed at 8, 12, 24, and 52 weeks.

PROJECTED ACCRUAL: A total of 90 patients will be accrued for this study.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed squamous cell carcinoma of the head and neck
• Stage II, III, or IV disease
• No evidence of distant metastases by chest x-ray, abdominal ultrasound, or CT scan (for patients with liver function abnormalities) or bone scan (for patients with local symptoms)
• Biopsy preferred unless medically contraindicated
• One of the following primary tumor sites:
• Oral cavity
• Oropharynx
• Hypopharynx
• Larynx
• Nasal cavity
• Paranasal cavity
• Unknown primary with metastasis to the head and neck region
• At least 1 uni- or bi-dimensionally measurable lesion
• No prior curative surgery for head and neck cancer
• Biopsy allowed

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• WHO 0-1

Life expectancy

• More than 12 weeks

Hematopoietic

• Neurophil count ≥ 2,000/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 10 g/dL

Hepatic

• Bilirubin normal
• AST and ALT ≤ 2.5 times upper limit of normal (ULN)*
• Alkaline phosphatase ≤ 5 times ULN* NOTE: *Patients with AST or ALT > 1.5 times ULN AND alkaline phosphatase > 2.5 times ULN are not eligible

Renal

• Creatinine clearance ≥ 60 mL/min

Cardiovascular

• No unstable cardiac disease despite treatment
• No myocardial infarction within the past 6 months

Pulmonary

• No chronic obstructive pulmonary disease requiring hospitalization within the past year

Other

• No symptomatic peripheral neuropathy ≥ grade 2
• No weight loss > 20% of body weight within the past 3 months (unless purposeful)
• No other malignancy within the past 3 years except adequately treated carcinoma of the cervix, basal cell or squamous cell skin cancer, or other cancer curatively treated by surgery
• Not pregnant or nursing

PRIOR CONCURRENT THERAPY: Biologic therapy

• No prior biologic therapy

Chemotherapy

• Prior induction chemotherapy for head and neck cancer allowed before radiotherapy begins

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy to the head and neck

Surgery

• See Disease Characteristics

Massachusetts
      Beth Israel Deaconess Medical Center, Boston,  Massachusetts,  02215,  United States; Recruiting
      Bethke Cancer Center at Emerson Hospital, Concord,  Massachusetts,  01742-4169,  United States; Recruiting
      Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute, Boston,  Massachusetts,  02115,  United States; Recruiting
      Hudner Oncology Center at Saint Anne's Hospital, Fall River,  Massachusetts,  02721,  United States; Recruiting
      Lowell General Hospital, Lowell,  Massachusetts,  01854,  United States; Recruiting
      NSMC Cancer Center - Peabody, Peabody,  Massachusetts,  01960,  United States; Recruiting
New Hampshire
      Seacoast Cancer Center at Wentworth-Douglass Hospital, Dover,  New Hampshire,  03820,  United States; Recruiting

Study chairs or principal investigators

Robert I. Haddad, MD,  Study Chair,  Dana-Farber/Harvard Cancer Center   

Study ID Numbers:  CDR0000393493; DFCI-03018; NCT00095927
Record last reviewed:  October 2004
Last Updated:  April 4, 2005
Record first received:  November 9, 2004
ClinicalTrials.gov Identifier:  NCT00095927
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08