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.