The purpose of this trial is to compare two different treatments for fit patients with head and neck cancer:

All patients are given induction-chemotherapy (docetaxel, cisplatin, 5-FU).

Subsequently patients are being randomised into two groups:

• The first group receives neo-adjuvant chemotherapy ('high' dose cisplatin) and conventional radiotherapy
• The second group receives neo-adjuvant chemotherapy ('low' dose cisplatin) and accelerated radiotherapy.

Induction Chemotherapy TPF(arm A and B)

: Docetaxel 75 mg/m2 iv on day 1, Cisplatin 75 mg/ m2 iv on day 1, 5-FU 750 mg/ m2/day iv continuous infusion (in Hickman or port a cath) on days 1-5; prophylactic G-CSF

This cycle will be repeated every 21 days for a maximum of 4 cycles. Clinical evaluation after each cycle and radiological evaluation after 2 cycles will take place. In case of PD or SD (after 2 cycles) with no minor response (no decrease in measurable disease from baseline) concomitant chemoradiotherapy will started per protocol.

Surgery The investigators in each centre can decide neck surgery for residual tumor

Inclusion Criteria:

Histology and staging disease

• Histologically or cytologically proven non-metastatic locally advanced HNSCC, stage III or IV, for which concomitant chemo-radiotherapy would be the standard therapy
• Patients can be included either with irresectable disease or for which the concomitant chemoradiotherapy was chosen for organ preservation
• Measurable disease
• Primary site: oral cavity, oropharynx, hypopharynx and larynx

General conditions

• Written informed consent
• Age >18 years and ≤ 65 years
• WHO performance status 0-1
• Adequate bone marrow function (WBC > 3.0 x 109/L, platelets > 100 x 109/L, Hb > 6 mmol/L)
• Adequate hepatic function: total bilirubin < 1. 5 x upper normal limit, ASAT and ALAT < 2.5 x upper normal limits
• Adequate renal function: calculated creatinin clearance > 60ml/min. (Cockcroft-Gault formula) Other
• Expected adequacy of follow-up.

Exclusion Criteria:

General conditions

• Active alcohol addiction
• Admission for COPD in the last 12 months
• Weight loss > 10% in 3 months before entry
• Pregnancy or lactation
• Patients (M/F) with reproductive potential not implementing adequate contraceptives measures

Prior or current history

• Prior surgery, radiotherapy or chemotherapy for this tumor
• Serious concomitant diseases preventing the safe administration of chemotherapy and/or radiotherapy or likely to interfere with the study assessments
• Serious active infections
• Other malignancies in the past 5 years with the exception of adequately treated carcinoma in situ of the cervix, or squamous or basal cell carcinoma of the skin

Concomitant treatments

• Concomitant (or within 4 weeks before randomisation) administration of any other experimental drug under investigation
• Concurrent treatment with any other anti-cancer therapy