The aim of this study is to evaluate if the multi modality treatment pemetrexed combined with cisplatin and radiotherapy can lead to a better tumor control and/or a better side-effect profile in patients with locally advanced NSCLC. Patients will be randomized between 3 cycles of induction chemotherapy followed by concurrent chemoradiotherapy or concurrent chemoradiotherapy followed by 3 cycles of adjuvant combination chemotherapy.

Inclusion Criteria:

• cytological or histological proven NSCLC
• unresectable stage III NSCLC
• presence of at least one measurable lesion (RECIST criteria)
• adequate haematological, renal and hepatic function
• adequate lung function reserve
• good condition, weight loss <10 % over previous 6 months, life expectancy > 3 months

Exclusion Criteria:

• previous chemo- or radiotherapy for NSCLC
• distant metastasis or a malignant pleural or pericardial effusion
• second active primary malignancy or serious concomitant medical disease
• interstitial lung disease
• auto-immune systemic disease with potential involvement of the lungs
• inability to interrupt aspirin or other non-steroidal anti-inflammatory agents for a 5-day period
• concomitant use of amiodarone