IFCT-GFPC 05.02 A Randomized Phase III Trial Assessing in Patients With Advanced Non-small Cell Lung Cancer

Inclusion Criteria: * Histologically documented NSCLC (tumor tissue samples will be provided to look for assessment of EGFR status with CISH, immunochemistry and mutations) : adenocarcinoma, squamous cell carcinoma, large cell carcinoma. A cytological documentation of NSCLC is accepted. * Stage IV disease or metastatic relapse in not previously irradiated areas of a NSCLC previously treated with surgery or radiation therapy (with a histologically documented proof of relapse) or stage III B with documented pleural involvement. * Measurable disease according to the RECIST criteria. * Prior radiotherapy authorized except for irradiation concerning measurable disease. * Age \>18 and \< 70 years. * PS \< 2. * Normal hepatic function : serum bilirubin \< 1.5 ULN, SGOT (ASAT) and SGPT (ALAT) \< 2,5 ULN ; in presence of liver metastases, SGOT and SGPT must be \< 5 x ULN. * Creatinine clearance \> 60 mL/min. * Granulocyte count \> 1,5 giga/L, platelet count \> 100 giga/L. * Life expectancy \> 12 weeks. * Written (signed) informed consent for use of tumors samples. * Written (signed) informed consent to participate in the sudy. Exclusion Criteria: * Small cell lung cancer, bronchiolo-alveolar carcinoma, neuro-endocrine carcinoma. * PS \> 1. * Prior chemotherapy other than cisplatin-gemcitabine. * Prior therapy with EGFR inhibitor (e.g. monoclonal antibody). * No concomitant therapy with phenytoin, carbamazepine, rifampicine or phenobarbital. * Concomitant radiotherapy except for localized bone irradiation. * Symptomatic brain metastases. * Superior vena cava syndrome. * Any unstable systemic disease : significant cardiovascular disease including myocardial infarction within the previous year, active infection, significant hepatic or renal disease. * Pre-existing interstitial lung disease. * Any inflammatory changes of the surface of the eyes. * Psychiatric disease with inability to understand the study or to comply with follow-up procedures. * Grade \> or = 2 peripheral neuropathy. * Any other malignancies within 5 years (except for treated carcinoma in situ of the cervix or basal cell skin cancer). * Pregnant or lactating women ; patients with reproductive potential must use effective contraception. * Inability to comply with follow-up procedures.