Radiation Therapy With or Without Chemotherapy in Reducing Mouth Dryness in Patients With Nasopharyngeal Cancer

Study Overview
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Brief Summary
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RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Giving radiation therapy in different ways may cause less damage to normal tissue, prevent or lessen mouth dryness, and may help patients live more comfortably. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with radiation therapy may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of specialized radiation therapy techniques with or without chemotherapy in reducing mouth dryness in patients who have nasopharyngeal cancer.

Detailed Description
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OBJECTIVES: Determine the transportability of IMRT to a multi-institutional setting. Determine the rate of late xerostomia in patients with nasopharyngeal cancer treated with intensity-modulated radiotherapy (IMRT) with or without chemotherapy. Correlate reduction of side effects on salivary flow with compliance in patients treated with these regimens. Determine the rate of local-regional control, distant metastasis, and disease-free and overall survival of patients treated with these regimens. Determine the acute and late toxicity of these regimens in these patients. Determine chemotherapy compliance in patients treated with these regimens. OUTLINE: Patients undergo daily intensity-modulated radiotherapy (IMRT) 5 days a week for approximately 6.5 weeks (total of 33 fractions) in the absence of disease progression or unacceptable toxicity. Patients with stage T2b or greater and/or node-positive disease receive cisplatin IV over 20-30 minutes on days 1, 22, and 43 concurrently with IMRT followed by cisplatin IV over 20-30 minutes and fluorouracil IV over 96 hours starting on days 71, 99, and 127. Quality of life is assessed through saliva measurement at baseline and then at 3, 6, and 12 months after IMRT. Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter. PROJECTED ACCRUAL: A total of 64 patients will be accrued for this study within 36-40 months.

Official Title
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A Phase II Study Of Intensity Modulated Radiation Therapy (IMRT) +/- Chemotherapy For Nasopharyngeal Cancer

Conditions
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Head and Neck Cancer, Oral Complications of Radiation Therapy, Radiation Toxicity

Intervention / Treatment
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* Drug: cisplatin
* Drug: fluorouracil
* Radiation: Intensity modulated radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed stage I-IVB squamous cell carcinoma of the nasopharynx WHO I-III No stage IVC disease No evidence of distant metastasis Measurable or evaluable disease Must have been treated with primary radiotherapy PATIENT CHARACTERISTICS: Age 18 and over Performance status Zubrod 0-1 Life expectancy Not specified Hematopoietic White blood cell count (WBC) at least 4,000/mm^3 Platelet count at least 100,000/mm^3 Hepatic Not specified Renal Creatinine no greater than 1.6 mg/dL Creatinine clearance at least 60 mL/min Other Not pregnant (If stage T2b or greater or node-positive disease) Negative pregnancy test (If stage T2b or greater or node-positive disease) No other prior head and neck cancer No other malignancy within the past 5 years except nonmelanoma skin cancer No active untreated infection No other major medical or psychiatric illness that would preclude study entry Nutritional and general physical condition compatible with radiotherapy NOTE: *If stage T2b or greater or node-positive disease PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy More than 6 months since prior chemotherapy Endocrine therapy Not specified Radiotherapy See Disease Characteristics More than 6 months since prior radiotherapy for head and neck cancer Surgery No prior head and neck surgery to the primary tumor or lymph nodes except incisional or excisional biopsies Other No other concurrent experimental therapy for cancer No amifostine or pilocarpine during or for 3 months after radiotherapy

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: IMRT +/- chemotherapy<br>Intensity modulated radiation therapy (IMRT) for all patients and chemotherapy (cisplatin and fluorouracil) for patients with stage ≥ T2b and/or N+ | Drug: cisplatin<br>* 100 mg/m^2 intravenously on days 1, 22, and 43 and 80 mg/m^2 intravenously on days 71, 99, and 127<br>Drug: fluorouracil<br>* 1000 mg/m^2/day as 96-hour continuous infusion on days 71-74, 99-102, and 127-130<br>Radiation: Intensity modulated radiation therapy<br>* The gross tumor and lymph node metastasis, Planning Target Volume (PTV) 70 (Clinical Target Volume [CTV] 70 with a 5 mm margin) will receive 70 Gy in 33 fractions at 2.12 Gy per fraction. Treatment will be delivered once daily, 5 fractions per week, over 6 weeks and 3 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Protocol Compliance of Intensity-modulated Radiotherapy Treatment Delivered | Patients scored by the study chairs as no variation or minor variation were considered compliant, while patients scored as major variation or inevaluable were considered non-compliant. The number being reported is the number non-compliant. A compliance rate of 90% was targeted with 75% or lower being considered unacceptable. Fifty-seven patients were required with types I and II error rates both 0.10. If 10 or more patients out of 57 were non-compliant, the treatment would be unacceptable, per a two-stage Fleming multiple testing procedure. | From start of treatment to end of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Xerostomia at 1 Year (Grade ≥ 2) |  | From start of treatment to 1 year | 
| Rate of Locoregional Control at 2 Years |  | From registration to 2 years | 
| Whole Mouth Saliva Output Relative to Pretreatment Measurements |  | From start of treatment to 1 year | 
| Other Acute and Late Toxicities |  | From start of treatment to last follow-up | 
| Chemotherapy Compliance |  | From start of treatment to end of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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oral complications of radiation therapy, radiation toxicity, stage I squamous cell carcinoma of the nasopharynx, stage II squamous cell carcinoma of the nasopharynx, stage III squamous cell carcinoma of the nasopharynx, stage IV squamous cell carcinoma of the nasopharynx