Radiation Therapy With or Without Combination Chemotherapy in Treating Patients With Advanced Cancer of the Oropharynx or Hypopharynx

OBJECTIVES:

• Compare the overall survival and survival without relapse for 1, 3, and 5 years of patients with squamous cell cancer of the oropharynx or hypopharynx after treatment with twice a day radiotherapy with or without cisplatin and fluorouracil.
• Compare the presence of distant metastases at 1, 3, and 5 years in these patients after these treatments.
• Compare the local control and duration of control in these patients after these treatments.
• Compare the clinical changes and histological changes at 6 months in these patients after these treatments.
• Determine the rate of complete response in these patients after these treatments.
• Determine the early and late toxic effects of these regimens in these patients.
• Determine the quality of life of these patients.
• Determine the pharmacokinetics of fluorouracil and tolerability of this regimen in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to center and primary site of disease (oropharynx vs hypopharynx)

Patients are randomized to one of two treatment arms.

• Arm I: Patients undergo radiotherapy twice a day, 6 hours apart, 5 days a week, for 7 weeks.
• Arm II: Patients undergo radiotherapy as in arm I, plus concurrent chemotherapy consisting of cisplatin IV on day 1 and fluorouracil by continuous infusion over 24 hours on days 1-5. Courses are repeated every 3 weeks for 3 courses.

Patients are followed every month for 1 year, every 2-3 months for 2 years, then every 6 months for at least 2 years.

PROJECTED ACCRUAL: A total of 160 patients (80/arm) will be accrued for this study within 4.5 years.

DISEASE CHARACTERISTICS:

• Histologically proven squamous cell cancer of the oropharynx or hypopharynx

• T4 and nonresectable OR
• T3 extended to oropharynx or hypopharynx and nonresectable
• N0-3 (stage III or IV)
• No distant metastases

PATIENT CHARACTERISTICS:

Age:

• 18 to 70

Performance status:

• Karnofsky 70-100%

Life expectancy:

• Greater than 3 months

Hematopoietic:

• Neutrophil count at least 2000/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin no greater than 1.25 times upper limit of normal (ULN)
• Transaminases no greater than 2.5 times ULN

Renal:

• Creatinine no greater than 1.25 times ULN

Cardiovascular:

• No severe cardiac disease

Other:

• No prior malignancy except basal cell skin cancer
• No uncontrolled infection

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior chemotherapy
• No concurrent antineoplastic therapy

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior radiotherapy

Surgery:

• No prior surgery (except biopsy or adenectomy)