Cetuximab & Concomitant-Boost Accelerated RT in Patients With Locally Advanced Oropharynx Squamous Cell Carcinoma.

The purpose of this study is to determine the 1-year rate of locoregional disease control in the experimental arm, using a control arm to avoid selection bias.

* To determine the 1-year rate of locoregional disease control in the experimental arm, using a control arm to avoid selection bias.
* To determine the 2 and 3 year rate of locoregional disease control.
* To evaluate the safety and toxicity of the combination of cetuximab and concomitant-boost accelerated radiotherapy followed by 12 weeks of complementary treatment with cetuximab. Both acute and chronic toxicity will be assessed.
* To determine specific disease-free survival, event-free survival, disease-specific survival and overall survival
* To determine acute and late toxicity
* To determine EGFR, p53, Ki67, and evaluate its value as a prognostic factor.

Eligibility Criteria:
Inclusion Criteria:

* Written informed consent.
* Aged between 18 and 80, inclusive.
* Karnofsky functional status \>= 70% at the time of enrolment in study.
* Life expectancy of more than 3 months.
* Histologically confirmed diagnosis of oropharyngeal squamous cell carcinoma: base of tongue, vallecula, tonsil and tonsillar fossa and pillars, glossotonsillar sulcus, inferior surface of the soft palate, uvula and lateral and posterior oropharyngeal wall.
* Stage III or IV with no evidence of distant metastasis (IVA or IV B)
* Patients in medical conditions to receive a radical concomitant-boost accelerated radiotherapy treatment.
* Neutrophils \>= 1500/ mm3, platelet count \>= 100 000/ mm3 and haemoglobin \>= 10 g/ dL.
* Proper liver function: total bilirubin \<= 1.5 x upper limit of normal (ULN); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \<= 2.5 x ULN.
* Proper renal function: serum creatinine \<= 1.5 x ULN; if the values are \> 1.5 x ULN, creatinine clearance should be \>= 55 ml/min.
* Serum calcium within normal limits.
* Adequate nutritional state: weight loss \< 20% with respect to usual weight and serum albumin \> 35 g/l.
* Effective birth control method if there is possibility of conception and/or pregnancy.
* Availability of tumour tissue for immunohistochemical analysis of EGFR expression.

Exclusion Criteria:

* Metastatic disease.
* Previous surgical, radiotherapy and/or chemotherapy treatment for the disease in the study.
* Other non-oropharyngeal tumour sites in the head and neck area.
* Other previous and/or simultaneous squamous cell carcinoma.
* Diagnosis of any other cancer in the previous 5 years, except properly treated carcinoma in situ of the uterine cervix and/or basal cell skin carcinoma.
* Active infection (infection requiring intravenous antibiotics), including active tuberculosis and diagnosed HIV.
* Uncontrolled hypertension defined as systolic blood pressure \>= 180 mm Hg and/or diastolic blood pressure \>= 130 mm Hg at rest.
* Pregnancy (absence of pregnancy must be confirmed with the serum-HCG test) or breast-feeding women.
* Chronic, concomitant systemic immunotherapy, or hormonal treatment for the cancer.
* Other concomitant anti-cancer treatments.
* Clinically significant coronary artery disease, history of myocardial infarction in the previous 12 months or high risk of out of control arrhythmia or cardiac insufficiency.
* Chronic obstructive pulmonary disease which may have required \> 3 hospitalisations in the previous 12 months.
* Out of control active peptic ulcer.
* Presence of a psychological or medical illness which might impede the patient from carrying out the study or giving his or her signature on the informed consent
* Known drug abuse (with the exception of excessive alcohol consumption)
* Known allergic reaction to any of the components of the treatment to be studied.
* Previous treatment with monoclonal antibodies or signal transduction inhibitors or other EGFR-targeted treatment.
* Any experimental treatment in the 30 days prior to enrolment in the study.