This Phase III trial aims to:

Explore the impact of pre-treatment information and radiation dose redistribution on locoregional control in patients with locally advanced SCCHN.

The dose to the primary tumor with margins, based upon PET and CT information, will be inhomogeneously increased to a tumor dose between 70 and 84 Gy with decreasing dose towards the edges of the irradiated area.

To determine the toxicity of combined modality treatment (cisplatin) with standard dose distribution versus combined modality treatment (cisplatin) with adaptive inhomogeneous radiation dose distribution.

Inclusion Criteria:

• biopsy-confirmed squamous cell carcinoma of the oropharynx, oral cavity or hypopharynx
• stage III/IV, T3-4, Nx M0
• < 70 yrs
• glomerular filtration rate (GFR) >60
• WHO 0-1
• no previous malignancies except for adequately treated basal cell carcinoma of the skin and carcinoma in situ of the cervix
• adequate bone marrow function, adequate hepatic function,informed consent
• >18 years

Exclusion Criteria:

• expected failure from follow-up
• previous malignancies except for adequately treated basal cell carcinoma of the skin and carcinoma in situ of the cervix
• expected inability to complete either one of the treatment arms
• pregnancy or lactation
• patients (m/f) with reproductive potential not implementing adequate contraceptive measures
• prior surgery, radiotherapy or chemotherapy for this tumor
• contraindications or serious concomitant diseases preventing the safe administration of chemotherapy and/or radiotherapy or are likely to interfere with the study assessments
• known active symptomatic fungal, bacterial and/or viral infections including HIV
• concomitant (or with 4 weeks before randomisation) administration of any other experimental drug
• concurrent treatment with any other anti-cancer therapy
• prior treatment with one or more of the active compounds