Evaluation of Afatinib in Maintenance Therapy in Squamous Cell Carcinoma of the Head and Neck

Inclusion Criteria:

* Age ≥ 18 years
* Histologically-confirmed diagnosis of non metastatic squamous-cell carcinoma of oral cavity ; oropharynx, larynx or hypopharynx.
* Macroscopically complete resection of disease.
* High-risk histological features defined as :

Microscopically incomplete tumour resection and/or invasion of regional lymph nodes with extracapsular extension (pN+R+)

* Indication of radio-chemotherapy (at least 60 Gy of radiotherapy and at least 2 cycles of chemotherapy)
* Start of radio-chemotherapy within 8 weeks after surgery
* Performance Status (PS) ECOG \<= 2
* Adequate Blood tests, renal and liver functions in the 15 days prior inclusion defined as :

Hemoglobin \> 9 g/dL Neutrophil count \> 1500 x 109/L Platelets \> 100 x 109/L Total bilirubin \< 1,5x upper limit of normal (ULN) SGOT and SGPT \< 2,5 x ULN Alkaline Phosphatase \< 2,5 xULN Serum creatinine \< 110 µmol/L or creatinine clearance \> 55 ml/min (estimated by Cockcroft Formula) Absence of proteinuria

* Women of childbearing age must use adequate means of contraception(oral hormon contraceptive, intrauterine contraceptive device, double barrier method of contraception).
* Mandatory affiliation with a healthy security insurance.
* Dated and signed written informed consent.

Exclusion Criteria:

* Macroscopic residual tumour after resection(R2)
* Metastatic disease
* Prior treatment for Head and neck cancer with chemotherapy, radiotherapy or any cancer target therapy
* Prior or concomitant malignancies (except for basal cell skin cancer ; in situ cervical carcinoma or other malignancies with a complete response \> 5 years)
* History of heavy hypersensibility reaction to Cisplatin
* Uncontrolled pulmonary, cardiac , hepatic or renal disease.
* History of interstitial pneumopathy
* Significant cardiovascular disease :

Congestive cardiac failure\> New York Heart Association (NYHA) Class II Myocardial infraction within 6 months prior to inclusion Unstable angina Severe cardiac arrythmia Uncontrolled hypertension while receiving appropriate medication (≥ 160 mm Hg systolic and/or ≥ 90 mm Hg diastolic) Disorder of left ventricular function with ejection fraction \< 50% Severe cerebrovascular accident within 6 months prior to inclusion History of severe thromboembolism within 6 months prior to inclusion Cardiovascular baseline QTcB \>480 ms (Calculated with Bazett Formula) Bradycardia Electrolytic disorders

\- Hepatic affection like : hepatitis B or C chronic advanced decompensated hepatitis hepatitic cirrhosis or newly treated chronic hepatitis or nowadays treated with immunosuppressive drugs severe auto-immune hepatitis or disease

* HIV known history
* Recent digestive symptoms with diarrhea as :

Crohn's disease malabsorption syndrome diarrhea Grade CTC ≥ 2

* Active drug or alcohol use or dependence
* Pregnant or breast-feeding women , or no use of effective birth control methods for women of childbearing potential, , or men who don't accept to use an effective birth control methods during the study
* Impossible follow-up