• Relapse-free survival [ Designated as safety issue: No ]
  

• Overall survival [ Designated as safety issue: No ]
  
• Local control without surgery [ Designated as safety issue: No ]
  
• Patterns of failure [ Designated as safety issue: No ]
  
• Acute and long-term toxicity [ Designated as safety issue: Yes ]
  
• Quality of life [ Designated as safety issue: No ]
  

OBJECTIVES:

• To compare the relapse-free survival of patients treated with radiotherapy and cisplatin with vs without fluorouracil.
• To compare the overall survival, local control without surgery, and patterns of failure in patients treated with these regimens.
• To compare the acute and long-term toxicity of these regimens in these patients.
• To compare the quality of life of patients treated with these regimens.
• To prospectively collect biopsy material, mucosal scrapings, and serum in an effort to generate hypotheses for future correlative studies.

OUTLINE: This is a multicenter study. Patients are stratified according to radiotherapy schedule (once daily vs twice daily) and radiotherapy planning (2D vs 3D vs intensity-modulated radiotherapy). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients undergo full-dose radiotherapy once or twice daily 5 days a week for up to 7 weeks and receive cisplatin IV over 1 hour on days 1, 22, and 43 of radiotherapy.
• Arm II: Patients undergo radiotherapy as in arm I and receive fluorouracil IV and cisplatin IV continuously on days 1-4 and 22-25 of radiotherapy.

Patients with biopsy-verified residual disease at the primary site or local recurrence after achieving a complete response to chemoradiotherapy may undergo salvage surgery 12 weeks after the completion of chemoradiotherapy.

Patients complete questionnaires periodically to assess late toxicity and quality of life.

After completion of study treatment, patients are followed periodically.

DISEASE CHARACTERISTICS:

• Histologically confirmed squamous cell carcinoma of the oral cavity, oropharynx, larynx, or hypopharynx

  • No histologic diagnosis other than squamous cell carcinoma
  • A primary site must be identified

• Must have locoregionally confined stage III (excluding T1-2, N1) or stage IV disease

  • No evidence of nodal disease below the clavicles or distant hematogenous metastases (M0)
  • No stage IVC disease (stage IVB disease allowed)

• Deemed appropriate for definitive non-operative management with curative intent

  • Resectable disease is not required
• No primary cancer of the nasopharynx, paranasal sinus, or salivary gland

PATIENT CHARACTERISTICS:

• ECOG performance status 0-1
• WBC > 3,500/mm³
• Platelet count > 100,000/mm³
• Serum creatinine < 2.0 mg/dL
• Alkaline phosphatase < 2 times normal
• AST < 2 times normal
• Bilirubin ≤ 2.0 mg/dL
• Serum calcium normal
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No unstable or uncontrolled angina
• No clinically apparent jaundice
• No active infection
• No history of any other malignancy (except squamous cell or basal cell skin cancer or cervical carcinoma in situ), unless the patient has been continuously disease-free for at least 5 years
• Not a poor compliance risk
• Able to withstand the rigors of intensive treatment
• Available for and compliant with adequate long-term follow-up

PRIOR CONCURRENT THERAPY:

• No prior definitive surgery or radiotherapy for this malignancy
• No prior chemotherapy, immunotherapy, or epidermal growth factor receptor inhibitors for any disease