The trial will compare the efficacy and safety of concomitant chemoradiation with tirapazamine, cisplatin and radiation versus cisplatin and radiation.

Inclusion Criteria:

• Previously untreated squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx.
• Stage III or IV disease (excluding T1N1, and T2N1 and metastatic disease).
• Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2.
• Absolute neutrophil count at least 1.5 X 10^9/L, platelet count at least 100 X 10^9/L, and hemoglobin > 9g/dL.
• Serum bilirubin < 1.25 times upper limit of normal (ULN) and aspartate aminotransferase (AST)/alanine transaminase (ALT) < 2.5 times ULN.
• Calculated creatinine clearance (Cockcroft-Gault) > 55 mL/min.

Exclusion Criteria:

• Metastatic Disease
• Primary cancers of the nasal and paranasal cavities and of the nasopharynx
• Significant intercurrent illness that will interfere with the Chemotherapy or Radiation Therapy during the trial
• Symptomatic peripheral neuropathy > grade 2
• Clinically significant hearing impairment
• Significant cardiac disease