The primary endpoint in this study is to investigate if there is a difference in overall survival in patients with locally advanced head and neck cancer, randomized to either radiotherapy and cetuximab or radiotherapy and cisplatin. A second randomization is performed in patients with T3-T4 tumors; allocated radiotherapy either 68.0 Gy or 73.1 Gy.

Inclusion Criteria:

• Age at least 18 years
• Histologically or cytologically confirmed , previous untreated head and neck squamous cell cancer of the oral cavity, hypopharynx, larynx or of the oral cavity aimed for unimodal treatment with radiotherapy with curative intent
• Tumor stage III and IV , but no evidence of distant metastases beyond the regional nodes in the neck
• WHO/Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• The patient must be expected to withstand radiotherapy combined with cisplatin or cetuximab
• The patient must be able to understand the information about the treatment and give a written informed concent to participate in the trial
• Adequate follow-up study must be possible; this will exclude a patient who is uncooperative
• Adequate renal function, creatinine clearance over 50 ml/min/1.73 estimated according to local practice at each study centre

Exclusion Criteria:

• Previous malignant disease in the head and neck region, with exception for basal cell carcinoma or curatively treated squamous cell carcinoma of the skin with follow-up time of at least 3 years
• Concomitant or previous malignancies. Exceptions are adequately treated basal cell carcinoma or squamous cell carcinoma of the skin, or in situ carcinoma of the cervix uteri, or other previous malignancy with a disease-free interval of at least 5 years
• Two or more synchronous primary head and neck squamous cell cancer at time of diagnosis
• Co-existing disease prejudicing survival (expected survival less than 6 months)
• Absolute neutrophil count less than 1.5 x 109/L
• Platelet count less than 100 x 109/L
• Bilirubin over 1.5 times upper limit of normal
• Aspartate aminotransferase (ASAT) or Alanine aminotransferase (ALAT) more than 3 times upper limit of normal
• Pregnancy or lactation
• Allergy to study drug or to the excipients in their formulation
• Neuropathy grade 2 or more according to Common terminology criteria for adverse events (CTCAE) v.4.0
• Hearing loss/tinnitus is a relative exclusion criteria; the responsible physician decides whether the patient may be included in the study
• Severe cardiac illness; myocardial infarction within 6 months prior to randomization, severe congestive heart failure, severe cardiomyopathy, ventricular arrythmia, unstable angina, uncontrolled hypertension