Inclusion Criteria:

- Histologically confirmed diagnosis of inoperable stage IIIB or IV primary pulmonary
nonsquamous NSCLC (according to UICC staging valid until 2008)

- Sufficient representative sample material for KRAS analysis

- Wild-type KRAS

- Informed consent of the patient

- Aged at least 18 years

- WHO Performance Status 0-2

- At least one unidimensional, measurable tumour parameter according to RECIST

- Life expectancy of al least 12 weeks

- Adequate haematological, hepatic, renal and metabolic function parameters:

- Leukocytes > 3000/mm³, ANC ≥ 1500/mm3, platelets ≥ 100,000/mm3, Creatinine
clearance ≥ 50 ml/min and serum creatinine ≤ 1.5 x upper limit of normal

- Bilirubin ≤ 1.5 x upper limit of normal, GOT-GPT ≤ 2.5 x upper limit of normal
in absence of liver metastases, or ≤ 5 x upper limit of normal in presence of
liver metastases, AP ≤ 5 x upper limit of normal

- Magnesium ≥ lower limit of normal; calcium ≥ lower limit of normal

Exclusion Criteria:

- Prior chemotherapy

- Clinically manifest, uncontrolled brain metastases

- Prior radiotherapy of the parameters to be measured

- Peripheral neuropathy NCI grade > 1

- Subject pregnant or breast feeding, or planning to become pregnant within 6 months
after the end of treatment.

- Subject (male or female) is not willing to use highly effective methods of
contraception (per institutional standard) during treatment and for 6 months (male or
female) after the end of treatment (adequate: oral contraceptives, intrauterine
device or barrier method in conjunction with spermicidal jelly).

- Serious concurrent diseases.

- Major surgery within the last 4 weeks before recruitment

- On-treatment participation in a clinical study in the period 30 days prior to
inclusion.

- Clinically significant cardiovascular disease in (incl. myocardial infarction,
unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac
arrhythmia) ≤ 1 year before enrolment.

- Ongoing or active infection, including active tuberculosis or known infection with
human immunodeficiency virus.

- Superior vena cava syndrome contraindicating hydration.

- History of interstitial lung disease, e.g. pneumonitis or pulmonary fibrosis or
evidence of interstitial lung disease on baseline chest CT scan.

- Patient with mild to moderate renal insufficiency who are unable to interrupt
salicylates (like aspirin) or other nonsteroidal anti-inflammatory drugs (NSAIDS) for
a 5-day period starting 2 days before administration of pemetrexed (8-day period for
long-acting agents such as piroxicam). Exception: Low dose aspirin (acetyl salicylic
acid) intake up to 150 mg per day is permitted without interruption.

- Presence of clinically significant third-space fluid collections, for example,
ascites or pleural effusions that cannot be controlled by drainage or other
procedures

- Inability or unwillingness to take folic acid, vitamin B12 supplementation or
dexamethasone (or equivalent corticosteroid); or any other inability to comply with
protocol or study related procedures

- Prior or concurrent malignancy (≤ 5 years prior to enrolment in study) except
non-melanoma skin cancer or cervical carcinoma FIGO stage 0-1 if the patient is
continuously disease-free

- Known allergic reactions on study medication