Cisplatin, Fluorouracil, Iressa, and Radiation Therapy Patients With Locally Advanced Head and Neck Cancer

OBJECTIVES:

Primary

• Explore the activity of cisplatin, fluorouracil, gefitinib, and hyperfractionated radiotherapy, in terms of 1-year survival and 1-year distant metastatic disease control, in patients with locally advanced squamous cell carcinoma of the head and neck.

Secondary

• Explore the activity of this regimen, in terms of disease-specific survival and local control, in these patients.
• Assess the toxicity of this regimen in these patients.
• Assess the complete response rate in patients treated with this regimen.
• Assess the toxicity and tolerability of long-term maintenance with gefitinib in patients rendered disease free after this treatment regimen.

OUTLINE: Patients undergo hyperfractionated radiotherapy twice daily, 5 days a week, beginning on day 1 and continuing for 6 weeks. Patients also receive fluorouracil IV continuously over 96 hours and cisplatin IV continuously over 96 hours on days 1-4 and 22-25 and oral gefitinib beginning once daily on day 1 and continuing for up to 2 years in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3-6 months.

PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed primary* squamous cell carcinoma of the head and neck region, excluding any of the following:

• Nasopharynx
• Paranasal sinuses
• Salivary glands NOTE: *Primary site must be identified
• Locoregionally confined stage III or IV disease

• No evidence of nodal disease below the clavicles
• No distant hematogenous metastases (M0)

PATIENT CHARACTERISTICS:

• ECOG performance status 0-1
• WBC > 3,500/mm³
• Platelet count > 100,000/mm³
• Creatinine ≤ 2.0 mg/dL
• Alkaline phosphatase < 2 times normal
• AST < 2 times normal
• Bilirubin ≤ 2.0 mg/dL
• Calcium normal
• Not pregnant or nursing
• Fertile patients must use effective contraception
• Must not be a poor compliance risk for follow-up
• No known severe hypersensitivity to gefitinib or any excipients of this drug
• No evidence of clinically active interstitial lung disease

• Patients with chronic, stable radiographic changes who are asymptomatic are eligible
• No unstable or uncontrolled angina, clinically apparent jaundice, or active infection
• No history of any other malignancy (except squamous cell or basal cell skin cancer or cervical carcinoma in situ) unless disease free for ≥ 5 years
• No other severe, uncontrolled systemic disease (e.g., unstable or uncompensated respiratory, cardiac, hepatic, or renal disease)

PRIOR CONCURRENT THERAPY:

• Recovered from prior oncologic or other major surgery
• No prior definitive surgery, radiotherapy, chemotherapy, immunotherapy, or epidermal growth factor receptor inhibitors for head and neck cancer
• No investigational drugs within the past 30 days
• No concurrent CYP3A4 inducers, including any of the following:

• Phenytoin
• Carbamazepine
• Rifampin
• Phenobarbital
• Hypericum perforatum (St. John's wort)
• Concurrent surgery allowed provided gefitinib is not administered 2 weeks before and 2 weeks after surgery
• No concurrent aminoglycoside antibiotics