Induction Chemotherapy Followed by Cetuximab Plus Definitive Radiotherapy Versus Radiation Plus Cisplatin

Inclusion Criteria: * \> 18 years of age * Histologically or cytologically confirmed diagnosis of HNSCC * Stage III/IV, not suitable for surgery (definitive cure rate improbable, technically unresectable or medical contraindication for surgery) * At least one uni-dimensional measurable lesion either by CT scan or MRI * Signed written informed consents prior to beginning protocol Specific procedures: * Tumor tissue available for immunohistochemical staining of EGFR expression and HPV * Life expectancy of \> 3 months at study entry * ECOG Performance Status of \<2 at study entry. * Effective contraception if risk of conception exists. * Neutrophils \> 2.0/mm³, platelet count \> 100,000/mm³, and hemoglobin \> 10 g/dl * Normal liver function * Serum creatinine \> 1.25 x ULN and/or creatinine clearance \> 60 ml/min Exclusion Criteria: * Prior systemic chemotherapy and/or radiotherapy * Known peripheral neuropathy \> grade 2 NCI-CTC version 3.0 * Known chronic heart failure * Prior surgery, excluding prior diagnostic biopsy * Known drug abuse * Active uncontrolled infection * Other concomitant anticancer therapy * Distant metastasis * Concurrent chronic systemic immune therapy, chemotherapy for disease other than cancer, or hormone therapy not indicated in the study protocol * Clinically relevant coronary artery disease or history of a myocardial infarction within the last 12 months before study entry * Medical or psychological condition that would not permit the patient to complete the trial or sign informed consent * Nasopharyngeal carcinoma WHO type II or III * Known allergic reaction against any of the components of the treatment * Pregnancy (absence confirmed by beta-HCG test) or lactation period * Any prior or on-going investigational medication * Previous or current malignancy except basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix