Inclusion Criteria:

• Signed written informed consent;
• Males or females between 18 and 70 years of age;
• Surgically resected squamous cell carcinomas of the hypopharynx, oropharynx, larynx and oral cavity with high risk of locoregional recurrence not more than 6-9 weeks (maximum) ago;

• To be categorized as high risk patients have to fulfil at least one of the following criterias:

  • R0 - resection <5 mm margin
  • R1 - resection
  • Extracapsular nodal extension;
• no previous chemotherapy, radiotherapy;
• Performance status ECOG: 0 - 1;
• Contraception in male and female patients if of childbearing potential, willingness to use effective contraceptive method for the study duration and 2 months post-dosing;

• Adequate renal, liver and hematological functions (within maximum 9 weeks until surgery):

  • Adequate bone marrow function: neutrophils > 1.5 x 10^9/L, platelets > 100 x 10^9/L, hemoglobin > 10.0 g/dL
  • Adequate liver function: Bilirubin < 2.0 mg/dL, AST, ALT, AP, γ-GT < 3 x ULN
  • Adequate renal function: creatinine clearance > =60 ml/min
• No distant metastases;

Exclusion Criteria:

• Nasopharyngeal carcinoma;
• R2 resection;
• Invalid informed consent;
• Performance Status > 1;
• Previous chemotherapy or radiotherapy for carcinoma of the head and neck;
• Prior exposure to EGFR pathway targeting therapy;

• Other serious illness or medical conditions:

  • Unstable cardiac disease despite treatment, congestive heart failure NYHA grade 3 and 4;
  • Clinically significantly abnormal electrocardiogram (ECG) or left ventricular ejection fraction (LVEF) below the institutional range of the normal
  • Significant neurologic or psychiatric disorders including dementia or seizures;
  • Active uncontrolled infection;
  • Active disseminated intravascular coagulation;
  • Other serious underlying medical conditions which could impair the ability of the patient to participate in the study;
• Symptomatic peripheral neuropathy National Cancer Institute-Common Toxicity Criteria (NCI-CTC v3.0) grade 2 or ototoxicity grade 2, except if due to trauma or mechanical impairment due to tumor mass;
• Having participated in another therapeutic clinical trial or any investigational agent in the preceding 30 days;
• Known allergic/hypersensitivity reaction to any of the components of the treatment;
• Pregnancy (absence confirmed by serum/urine β-HCG) or breast-feeding;
• Known drug abuse;
• Other previous malignancy within 5 years, with exception of a history of a previous basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix;
• Legal incapacity or limited legal capacity;
• Sensitivity and incompatibility against 5-Fluorouracil
• Sensitivity and incompatibility against platinum-componds
• Known incompatibilites >grade 3 towards cetuximab
• expected incompliance of patient (e.g. in case of severe alcohol addiction)
• Dental evaluation: Pre treatment dental care before start of radiochemotherapy (approximately 8 to 10 days lapse-time is needed for complete recovery before initiation of radiation therapy).