cetuximab & concomitant-boost accelerated rt in patients with locally advanced oropharynx squamous cell carcinoma.

Conditions: Oropharyngeal Neoplasms

Summary: 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, creatinine clearance should be \>= 55 ml/min. * serum calcium within normal limits. * adequate nutritional state: weight loss \ 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.

Keywords: oropharyngeal neoplasms cetuximab concomitant-boost accelerated radiotherapy