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.