The general aim is to compare the cumulative dose of cisplatin administered concomitantly with radiotherapy in reference arm A (cisplatin 100 mg / m2 day 1 every 21 days) and in the experimental arm B (Cisplatin split 25 mg / m2 / J D1 to D4 all 21 days).

The standard treatment for squamous cell carcinoma of the head and neck locally advanced non-operated or non-operable is a combination of radiotherapy and concomitant chemotherapy. Indeed, the meta-analysis MACH showed for RT / CT associations an absolute survival benefit of 8% compared with radiotherapy alone. Cisplatin delivered optimally, ie at a dose of 100 mg / m2 on day 1, D22 and D43 of radiotherapy is as effective as combinations of cisplatin and 5-fluorouracil.

In post operative, treatment of high risk recurrence forms by Cisplatin, concomitantly with radiotherapy, also increases local control and overall survival.

However, it is an association whose toxicity is significant. The usual limiting toxicities were mucositis, dysphagia, nausea and vomiting with malnutrition and biologically kidney failure and myelotoxicity. Only 2/3 of the patients receive 3 cycles of cisplatin initially programmed.

As shown in the RTOG 0129 trial, the number of cycles of cisplatin and thus the cumulative dose of cisplatin administered concurrently with radiation therapy, significantly influences the locoregional control, progression free survival and overall survival.

One method of reducing the toxicity and thereby, increase the cumulative dose, would be to split the administration of cisplatin.

Moreover, the efficacy of Cisplatin, which only the free fraction is active, seems correlated with AUC that peak plasma which would in turn responsible for toxicity. The completion of a pharmacokinetic study comparing the AUC and Cmax obtained with cisplatin 100 mg / m2 and cisplatin fractionated is essential.

Finally, the limiting renal toxicity induced by cisplatin is currently diagnosed using the creatinine clearance. The Neutrophil gelatinase-associated lipocalin (NGAL) urinary is a new diagnosis and prognosis marker of renal impairment following treatment with cisplatin. However, further studies are needed to validate its clinical utility.

Inclusion Criteria:

• Squamous cell carcinoma of head and neck cancer stage III or IV: oral cavity, oropharynx, larynx or hypopharynx.
• Patient non-operated and / or inoperable for reasons of non extirpabilité, local and regional expansion, general state or medical condition Or
• Patient operated within 8 weeks before radiation therapy with a high risk of recurrence: unsatisfactory surgical margins (R1) and / or lymph node involvement with capsular rupture.
• Activity Index according to WHO ≤ 2
• Age ≤ 70 years
• Ventricular ejection fraction left retained> 50%
• Renal allowing the administration of cisplatin: creatinine clearance> 60 ml / min (Cockroft formula)
• Hematologic function allowing administration of CT: PNN> 1500, Pl> 100000, Hb> 9g
• Satisfactory Liver function: SGOT and SGPT <3N; total bilirubin <20 mg / dL; INR <1.5; albumin> 30 g / l
• Stomatological care adapted
• Signature of informed consent
• Bilateral neck irradiation Indication
• Women and men of reproductive age should have accepted a medically effective contraception during the treatment period and at least 6 months after discontinuation of study treatment. If pregnancy is declared by a patient or partner of a patient, it must be followed for know the evolution of pregnancy.

Exclusion Criteria:

• Cancers of the nasopharynx, sinus or nasal cavities
• Histology other than squamous
• Presence of distant metastases
• Prior systemic chemotherapy (neoadjuvant)
• Other concomitant cancer therapies
• Presence of infection requiring the use of IV antibiotics including tuberculosis and HIV infection
• Coronary insufficiency, cardiac arrhythmias, uncontrolled or symptomatic heart failure
• Uncontrolled hypertension
• Peripheral neuropathy grade> 1
• Vaccination against yellow fever and phenytoin recent or planned
• History of cancer within 5 years prior to trial entry other than cutaneous basal cell carcinoma in situ or cervical
• Pregnant woman capable of being or during lactation
• Persons deprived of liberty, under guardianship
• Inability to submit to medical monitoring testing for geographical, social or psychic
• Unilateral cervical radiotherapy Indication