The purpose of this study is to evaluate the safety of adding the investigational drug Motexafin Gadolinium to the standard treatment of radiation therapy and chemotherapy with drugs called 5-FU and cisplatin in patients with advanced head and neck cancer.

Inclusion Criteria:

• At least 18 years of age
• Each patient must sign a study-specific informed consent form
• Newly diagnosed, locally advanced, non-metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN) arising from a primary site in the oropharynx, hypopharynx, or larynx confirmed by evaluation of fine needle aspiration or biopsy samples and MRI
• Eligible for curative intent treatment with hyperfractionated radiation and concurrent 5-FU and cisplatin
• Karnofsky Performance Status score of at least 60%
• Primary tumor at least 4 cm in diameter

Exclusion Criteria:

Laboratory Values of:

• Serum creatinine > 1.8 mg/dL; unless 24-hour urine creatinine clearance is ≥ 70 mL/min
• Serum total bilirubin > 1.5 times the upper limit of normal
• ALT (formerly SGPT) > 1.5 times the upper limit of normal
• Alkaline phosphatase > 1.5 times the upper limit of normal
• Absolute neutrophil count (ANC) < 1500/L
• Platelet count < 100,000/L
• 3+ or greater proteinuria on urinalysis

and

• Squamous Cell Carcinoma of the Head and Neck arising from a primary site in the oral cavity or nasopharynx
• Distant metastases
• Prior history of cancer at any site treated with radiotherapy and/or chemotherapy
• History of SCCHN diagnosed within 5 years of current diagnosis