RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Cisplatin and paclitaxel may make tumor cells more sensitive to radiation therapy. Giving more than one drug (combination chemotherapy) and giving them with radiation therapy may kill more tumor cells. It is not yet known whether giving radiation therapy together with combination chemotherapy is more effective than giving combination chemotherapy alone in treating head and neck cancer.

PURPOSE: This randomized phase III trial is studying radiation therapy and combination chemotherapy to see how well they work compared to combination chemotherapy alone in treating patients with recurrent head and neck cancer that cannot be removed by surgery.

Condition	Intervention	Phase
recurrent squamous cell carcinoma of the hypopharynx recurrent squamous cell carcinoma of the larynx recurrent squamous cell carcinoma of the lip and oral cavity recurrent squamous cell carcinoma of the oropharynx recurrent metastatic squamous neck cancer with occult primary recurrent lymphoepithelioma of the oropharynx	Drug: cisplatin  Drug: docetaxel  Drug: filgrastim  Drug: fluorouracil  Drug: paclitaxel  Procedure: biological response modifier therapy  Procedure: chemotherapy  Procedure: colony-stimulating factor therapy  Procedure: cytokine therapy  Procedure: radiation therapy  Procedure: radiosensitization	Phase III

Further Study Details: 

OBJECTIVES: Primary

• Compare overall survival of patients with previously irradiated unresectable locally recurrent squamous cell carcinoma of the head and neck treated with radiotherapy, cisplatin, and paclitaxel vs cisplatin-based chemotherapy alone.

Secondary

• Compare progression-free survival of patients treated with these regimens.
• Compare the toxicity of these regimens in these patients.
• Compare quality of life, functional/performance status, and quality-adjusted survival of patients treated with these regimens.

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

• Arm I: Patients undergo radiotherapy twice daily and receive paclitaxel IV over 1 hour and cisplatin IV over 30 minutes once daily on days 1-5, 15-19, 29-33, and 43-47. Patients also receive filgrastim (G-CSF) subcutaneously once daily on days 6-13, 20-27, 34-41, and 48-55.
• : Patients receive 1 of the following cisplatin-based* regimens at the discretion of the treating physician:
• Regimen 1: Patients receive cisplatin* IV over 1-2 hours on day 1 and fluorouracil IV continuously over 96 hours on days 1-4.
• Regimen 2: Patients receive cisplatin* IV over 1-2 hours and paclitaxel IV over 3 hours on day 1.
• Regimen 3: Patients receive cisplatin* IV over 1-2 hours and docetaxel IV over 1 hour on day 1. NOTE: *Carboplatin may be substituted for cisplatin in patients with creatinine clearance < 50 mL/min or in patients who experience grade 2 or 3 neurotoxicity.

For all regimens, treatment repeats every 21 days for at least 6 courses in the absence of disease progression or unacceptable toxicity. Patients achieving complete response (CR) receive 2 additional courses beyond documentation of CR.

Quality of life is assessed at baseline and then at 3, 6, 12, 24, and 36 months.

After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 240 patients (120 per treatment arm) will be accrued for this study within 5½ years.

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

Criteria

DISEASE CHARACTERISTICS:

• Histologically* or cytologically* confirmed squamous cell carcinoma (SCC) of the oral cavity, oropharynx, hypopharynx, or larynx, including any of the following histologic variants:
• Spindle cell carcinoma
• Poorly differentiated keratin-positive carcinoma
• Lymphoepithelioma NOTE: *Biopsy or primary tumor and/or fine needle aspiration of the metastatic lymph node required
• Original or second primary tumor
• Recurrent neck metastases with unknown primary allowed
• Locally recurrent disease
• Measurable disease
• Unresectable disease
• Attempted surgical resection allowed provided surgery was performed ≥ 3 months ago, wound is completely healed, and there is no sign of carotid exposure
• Must have had prior radiotherapy for SCC of the head and neck with > 75% of the present tumor volume in areas irradiated at doses ≥ 45 Gy but ≤ 75 Gy
• Able to successfully re-irradiate the area of the gross tumor volume without exceeding lifetime spinal cord dose of 54 Gy as determined by physical examination and CT scan and/or MRI performed within the past 8 weeks
• First recurrence occurred > 6 months after completion of radiotherapy
• More than 1 recurrence allowed provided the above criteria for first recurrence has been met
• No primary tumor of the nasopharynx or salivary gland
• No distant metastases by history or physical examination, chest CT scan, and CT scan or MRI of the tumor site
• Patients with equivocal pulmonary nodules are eligible provided the nodules are < 1 cm, can be safely biopsied, or are negative by positron emission tomography imaging
• No circumferential tumor involvement of the carotid sheath by imaging unless prophylactic carotid stent is placed

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• Zubrod 0-1

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,800/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 8.0 g/dL (transfusion or other intervention allowed)

Hepatic

• AST or ALT < 2 times upper limit of normal (ULN)
• Bilirubin < 1.5 mg/dL
• No hepatic insufficiency resulting in clinical jaundice and/or coagulation defects

Renal

• Creatinine clearance > 50 mL/min
• Calcium < 11.5 mg/dL

Cardiovascular

• No New York Heart Association class III or IV heart disease
• No other symptomatic or uncontrolled cardiac disease

Pulmonary

• No chronic obstructive pulmonary disease exacerbation
• No other respiratory illness requiring hospitalization within the past 6 months or that would preclude study therapy

Immunologic

• No AIDS
• No prior allergic reaction to E. coli-derived products
• No acute bacterial or fungal infection requiring IV antibiotics

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 30 days after completion of study treatment
• No other invasive malignancy within the past 3 years except nonmelanoma skin cancer, carcinoma in situ of the breast, oral cavity, or cervix
• No pre-existing peripheral sensory neuropathy > grade 2
• No other severe active co-morbidity

PRIOR CONCURRENT THERAPY: Biologic therapy

• Not specified

Chemotherapy

• At least 6 months since prior chemotherapy
• No prior systemic chemotherapy for recurrent SCC of the head and neck
• Prior neoadjuvant, adjuvant, and/or concurrent chemotherapy and radiotherapy for initial SCC of the head and neck allowed

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics
• See Chemotherapy
• At least 6 months since prior radiotherapy

Surgery

• See Disease Characteristics

Other

• Prior cyclooxygenase-2 inhibitor or retinoids for chemoprevention allowed
• At least 6 months since prior epidermal growth factor receptor (EGFR) inhibitors or other targeted agents
• No prior EGFR inhibitors or other targeted agents for recurrent SCC of the head and neck
• No concurrent cimetidine or allopurinol (for patients on arm II, regimen 1)

Please refer to this study by ClinicalTrials.gov identifier  NCT00113399

Michigan
      Bronson Methodist Hospital, Kalamazoo,  Michigan,  49007,  United States; Recruiting
      West Michigan Cancer Center, Kalamazoo,  Michigan,  49007,  United States; Recruiting
Nevada
      CCOP - Southern Nevada Cancer Research Foundation, Las Vegas,  Nevada,  89106,  United States; Recruiting
North Carolina
      Lenoir Memorial Cancer Center, Kinston,  North Carolina,  28501,  United States; Recruiting
Wisconsin
      Medical College of Wisconsin Cancer Center, Milwaukee,  Wisconsin,  53226,  United States; Recruiting

Study chairs or principal investigators

Stuart J. Wong, MD,  Principal Investigator,  Medical College of Wisconsin   

Study ID Numbers:  CDR0000429480; RTOG-0421; ECOG-R0421; NCT00113399
Record last reviewed:  May 2005
Last Updated:  June 30, 2005
Record first received:  June 7, 2005
ClinicalTrials.gov Identifier:  NCT00113399
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-07-05