Inclusion Criteria:

1. Histologic or cytologic diagnosis of NSCLC, Stage IV or selected stage IIIB (with
malignant pleural or pericardial effusion) according to the American Joint Committee
on Cancer (AJCC).

2. In phase I, previous chemotherapy including cytotoxic chemotherapy except for
irinotecan and cisplatin therapy, targeted therapy and/or radiotherapy is allowed;
patients are required to have discontinued previous anti-tumor treatment for at least
4 weeks. Neoadjuvant chemotherapy or adjuvant chemotherapy is allowed and regarded as
one-time systemic chemotherapy.

3. In phase II, no prior chemotherapy, radiotherapy or target therapy is allowed. (Prior
radiation therapy is allowed as long as the irradiated area is not the only source of
measurable disease. Neoadjuvant chemotherapy or adjuvant chemotherapy is not
allowed.)

4. Performance status of 0, 1, 2 on the ECOG criteria.

5. At least one uni-dimensionally measurable lesion meeting Response Evaluation Criteria
in Solid Tumors (RECIST 2000).

6. Estimated life expectancy of at least 12 weeks.

7. Patient compliance that allows adequate follow-up.

8. Adequate organ function.

9. Metastasis of CNS is not regard to exclusion if the symptom is controlled properly
for supportive care including corticosteroid.

10. Informed consent from patient

11. If female: childbearing potential either terminated by surgery, radiation, or
menopause, or attenuated by use of an approved contraceptive method (intrauterine
device [IUD], birth control pills, or barrier device) during and for 3 months after
trial. If male, use of an approved contraceptive method during the study and 3 months
afterwards. Females with childbearing potential must have a urine negative hCG test
within 7 days prior to the study treatment.

Exclusion Criteria:

1. MI within preceding 6 months or symptomatic heart disease, including unstable angina,
congestive heart failure or uncontrolled arrhythmia

2. Serious concomitant infection including post-obstructive pneumonia

3. Second primary malignancy (except in situ carcinoma of the cervix or adequately
treated basal cell carcinoma of the skin or prior malignancy treated more than 5
years from the diagnosis without recurrence)

4. Pregnant or nursing women

5. Psychiatric disorder that would preclude compliance.

6. Major surgery other than biopsy within the past two weeks.

7. Patients receiving a concomitant treatment with drugs interacting with S-1 such as
flucytosine, phenytoin, or warfarin et al.