Paclitaxel, Cisplatin, and Filgrastim Combined With Radiation Therapy in Treating Patients With Locally Recurrent 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 tumor cells from dividing so they stop growing or die. Colony-stimulating factors such as filgrastim may increase the number of immune cells found in bone marrow or peripheral blood and may help a person's immune system recover from the side effects of chemotherapy. Radiation therapy uses high-energy x-rays to damage tumor cells. PURPOSE: Phase II trial to study the effectiveness of paclitaxel, cisplatin, and filgrastim combined with radiation therapy in treating patients who have locally recurrent head and neck cancer and have received previous treatment with radiation therapy.

Detailed Description
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OBJECTIVES: Determine the median, one-year, and long-term (defined as two-year) disease-free survival and overall survival in patients with previously irradiated locally recurrent squamous cell cancer of the head and neck treated with paclitaxel, cisplatin, and filgrastim (G-CSF) combined with radiotherapy. Determine the rates of acute and late toxic effects of this regimen in these patients. Determine the pattern of disease progression in patients treated with this regimen. OUTLINE: Patients undergo radiotherapy twice daily (4-6 hours apart) on days 1-5. Patients receive paclitaxel IV over 1 hour beginning immediately after completion of the first fraction of radiotherapy and completing less than 3 hours before starting the second fraction of radiotherapy on days 1-5. Patients receive cisplatin IV over 30 minutes beginning immediately after completion of paclitaxel infusion on days 1-5 and filgrastim (G-CSF) subcutaneously on days 6-13. Treatment repeats every 2 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Patients who initially respond to therapy but develop a recurrence with a resectable lesion (inside or outside the retreatment field) may undergo surgical resection. Patients are followed at 4 weeks after completion of radiotherapy, every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter. PROJECTED ACCRUAL: A total of 100 patients will be accrued for this study within 34 months.

Official Title
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Phase II Study of Paclitaxel and Cisplatin in Combination With Split Course Concomitant Hyperfractionated Re-Irradiation in Patients With Recurrent Squamous Cell Cancer of the Head and Neck

Conditions
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Head and Neck Cancer

Intervention / Treatment
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* Biological: filgrastim
* Drug: cisplatin
* Drug: paclitaxel
* Procedure: conventional surgery
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically proven locally recurrent primary squamous cell cancer (SCC) of the head and neck or second primary SCC of the head and neck More than 1 prior recurrence allowed if the first recurrence occurred at least 6 months after completion of prior radiotherapy Disease must be confined to the head and neck (above the clavicles) No primary SCC of the nasopharynx or salivary gland Prior irradiation of 45-75 Gy to the majority (75% or greater) of tumor volume Entire tumor volume must be included in a treatment field that limits the total spinal cord dose (prior and anticipated) to 50 Gy Prior radiotherapy records, including simulation and portal films, available in order to assure that cord tolerance is not exceeded Measurable disease Ineligible for complete surgical resection No distant metastases PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Zubrod 0 or 1 Life expectancy: No other concurrent illness that would limit survival Hematopoietic: Granulocyte count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hepatic: Bilirubin no greater than 1.5 mg/dL Serum glutamate oxaloacetate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) no greater than 2 times normal* Alkaline phosphatase no greater than 2 times normal* * Greater than 2 times normal allowed if no metastases by liver ultrasound or CT scan Renal: Creatinine no greater than 1.5 mg/dL Other: No other invasive malignancy within the past 2 years except in situ malignancies (e.g., carcinoma in situ of the cervix, carcinoma in situ of the breast, or nonmelanoma skin cancer) No other concurrent illness that would impair tolerance to therapy No grade 2 or worse pre-existing peripheral sensory neuropathy No hypersensitivity to E. coli derived products Not pregnant or nursing Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: Prior chemotherapy allowed as a component of the primary treatment No prior chemotherapy for recurrent disease At least 6 months since prior chemotherapy Endocrine therapy: Not specified Radiotherapy: See Disease Characteristics At least 6 months since prior radiotherapy Surgery: See Disease Characteristics

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: Radiation (BID) and chemotherapy<br>Radiation (BID), cisplatin and paclitaxel given on days 1-5 (Monday-Friday) in weeks 1, 3, 5 and 7. G-CSF given on days 6-13. | Biological: filgrastim<br> <br> Drug: cisplatin<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 |
| --- | --- | --- |
| Overall Survival |  | From registration to 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-free Survival |  | From registration to 1 year | 
| Grade 4-5 toxicity |  | From one year after the start of radiation therapy to last follow-up. | 
| Pattern of failure (local-regional, distant, new primary, death) |  | From registration to 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 oropharynx, stage I squamous cell carcinoma of the hypopharynx, stage II squamous cell carcinoma of the hypopharynx, stage III squamous cell carcinoma of the hypopharynx, recurrent squamous cell carcinoma of the hypopharynx, stage I squamous cell carcinoma of the larynx, recurrent metastatic squamous neck cancer with occult primary, metastatic squamous neck cancer with occult primary squamous cell carcinoma, stage I squamous cell carcinoma of the lip and oral cavity, stage II squamous cell carcinoma of the lip and oral cavity, stage III squamous cell carcinoma of the lip and oral cavity, recurrent squamous cell carcinoma of the lip and oral cavity, stage I squamous cell carcinoma of the oropharynx, stage II squamous cell carcinoma of the oropharynx, stage III squamous cell carcinoma of the oropharynx, stage II squamous cell carcinoma of the larynx, stage III squamous cell carcinoma of the larynx, recurrent squamous cell carcinoma of the larynx, stage I squamous cell carcinoma of the paranasal sinus and nasal cavity, stage II squamous cell carcinoma of the paranasal sinus and nasal cavity, stage III squamous cell carcinoma of the paranasal sinus and nasal cavity, recurrent squamous cell carcinoma of the paranasal sinus and nasal cavity