Head and Neck Cancer, Oral Complications of Radiation Therapy, Radiation Toxicity
Conditions
Keywords
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
Brief summary
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
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.
Interventions
DRUGcisplatin
100 mg/m\^2 intravenously on days 1, 22, and 43 and 80 mg/m\^2 intravenously on days 71, 99, and 127
DRUGfluorouracil
1000 mg/m\^2/day as 96-hour continuous infusion on days 71-74, 99-102, and 127-130
RADIATIONIntensity modulated radiation therapy
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.
Sponsors
National Cancer Institute (NCI)
Radiation Therapy Oncology Group
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Protocol Compliance of Intensity-modulated Radiotherapy Treatment Delivered | From start of treatment to end of treatment | 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. |
Secondary
| Measure | 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| IMRT +/- Chemotherapy Intensity modulated radiation therapy (IMRT) for all patients and chemotherapy (cisplatin and fluorouracil) for patients with stage ≥ T2b and/or N+ | 68 |
| Total | 68 |
Baseline characteristics
| Characteristic | IMRT +/- Chemotherapy |
|---|---|
| Age, Continuous | 48.5 years |
| Gender Female | 17 Participants |
| Gender Male | 51 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 68 / 68 |
| serious Total, serious adverse events | 55 / 68 |
Outcome results
Primary
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.
Time frame: From start of treatment to end of treatment
Population: First 57 eligible patients who started study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IMRT +/- Chemotherapy | Protocol Compliance of Intensity-modulated Radiotherapy Treatment Delivered | 9 participants |
Secondary
Chemotherapy Compliance
Time frame: From start of treatment to end of treatment
Secondary
Other Acute and Late Toxicities
Time frame: From start of treatment to last follow-up
Secondary
Rate of Locoregional Control at 2 Years
Time frame: From registration to 2 years
Secondary
Rate of Xerostomia at 1 Year (Grade ≥ 2)
Time frame: From start of treatment to 1 year
Secondary
Whole Mouth Saliva Output Relative to Pretreatment Measurements
Time frame: From start of treatment to 1 year