To determine safety profile of the epidermal growth factor receptor (EGFR) antagonist, ZD1839 in combination with cisplatin and radiation therapy in patients with local-regional recurrent squamous cell cancer of the head and neck.

To study the effects of ZD1839 combined with either cisplatin or radiotherapy on signal transduction pathway gene expression in tumor cells in patients with local-regional recurrent squamous cell cancer of the head and neck using micro array analysis from tumor samples taken at the time of relapse and during treatment.

Inclusion Criteria:- Patients must have pathologically confirmed recurrence (reappearance of previously cleared) squamous cell cancer primary in the upper aerodigestive tract or a second squamous cell primary (excluding nasopharynx or salivary gland tumors). Patients may have experienced more than one recurrence as long as the first recurrence occurred greater than or equal to 6 months following the end of the prior RT.

• The recurrence or second primary must have defined bi- or uni-dimensional measurements.
• Recurrence or second primary must be confined to the head and neck above the clavicles (loco-regional recurrence).
• The patient must not be a candidate for complete surgical resection. The previous irradiation must not exceed a maximum of 75 Gy.
• The entire tumor volume must be included in a treatment field that limits the total spinal cord dose to 50 Gy (prior RT and anticipated RT).
• Patients must be at least 6 months from prior radiation therapy.
• Patients may have received prior chemotherapy as a component of their primary treatment, but not for recurrent disease.
• Zubrod performance status 0-1.
• Granulocytes greater than or equal to 1500/mm3, platelets greater than or equal to 100,000/mm3, serum bilirubin less than or equal to 1.5 mg/dl, creatinine less than or equal to 1.5 mg/dl within 2 weeks prior to registration.
• LFT's less than or equal to 2 x normal (SGOT/SGPT/Alkaline Phosphatase). If greater than 2 x normal, liver ultrasound or CT is required to exclude metastases. If negative for metastases, patients are eligible.
• Must be able to submit previous radiation records, including simulation and portal films, in order to assure that cord tolerance is not exceeded.
• Patients must sign a study-specific informed consent form prior to study entry. Exclusion Criteria:- Primary in the nasopharynx or the salivary gland.
• Intercurrent medical illnesses which would impair patient tolerance to therapy or limit survival.
• A history of allergic reactions attributed to compounds of similar chemical or biologic composition to ZD1839 or other agents used in study.
• Pregnant and nursing women are excluded because of the potential teratogenic effects and potential unknown effects on nursing newborns.