Combination Chemotherapy With or Without Radiation Therapy in Treating Patients With Recurrent Head and Neck Cancer That Cannot Be Removed By Surgery

Study Overview
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Brief Summary
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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.

Detailed Description
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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. Arm II: 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.

Official Title
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A Phase III Trial for Locally Recurrent, Previously Irradiated Head and Neck Cancer: Concurrent Re-Irradiation and Chemotherapy Versus Chemotherapy Alone

Conditions
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Head and Neck Cancer

Intervention / Treatment
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* Biological: filgrastim
* Drug: cisplatin
* Drug: docetaxel
* Drug: fluorouracil
* Drug: paclitaxel
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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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/mm³ Platelet count ≥ 100,000/mm³ 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)

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Radiotherapy and chemotherapy<br>Radiotherapy/paclitaxel/cisplatin/filgrastim | Biological: filgrastim<br> <br> Drug: cisplatin<br> <br> Drug: paclitaxel<br> <br> Radiation: radiation therapy<br> <br> |
| Other: Chemotherapy<br>Cisplatin/fluorouracil/paclitaxel/docetaxel | Drug: cisplatin<br> <br> Drug: docetaxel<br> <br> Drug: fluorouracil<br> <br> Drug: paclitaxel<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival |  | Date of death or last follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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