Trial Information

A Phase II Study of Gefitinib in Benefited Patients With Asymptomatic Brain Metastasis Advanced Non-Small Cell Lung Cancer by Chemotherapy

Inclusion criteria:

1. Histological or cytological documented stage IV NSCLC. Sputum cytology alone is
excluded.

2. Extracerebral lesions show stable disease after first line chemotherapy. Patient has
recovered from CTCAE grade 3/4 toxicity. Patients who had never received EGFR-TKI or
EGFR monoclonal antibody.

3. Patients must be at least 18 years.

4. ECOG Performance Status 0, 1 or 2.

5. Life expectancy of at least 12 weeks.

6. Appraisable disease, the presence of at least three lesions if longest diameter <10 mm
by brain MRI.

7. Haemoglobin ³ 10.0 g/dl, Absolute neutrophil count (ANC) ³1.5 x 109/L, platelets ³ 100
x 109/L.

8. Total bilirubin £ 1.5 x upper limit of normal (ULN)

9. ALT and AST < 2.5 x ULN in the absence of liver metastases, or < 5 x ULN in case of
liver metastases.

10. Creatinine clearance ³ 60ml/min (calculated according to Cockcroft-gault formula).

11. PT-INR/PTT < 1.2 x ULN.

12. Written informed consent.

13. Able to comply with study and follow-up procedures.

Exclusion criteria:

1. Mixed small cell and non-small cell lung cancer histology.

2. Any unresolved toxicity>CTCAE grade 2 from previous anti-cancer therapy.

3. Patients with exposure to biotherapy, immunotherapy within 4 weeks of study entry.

4. Other concurrent anticancer therapy.

5. Patients with exposure to investigational drug therapy outside of this trial.

6. Lack of physical integrity of the upper gastrointestinal tract, or malabsorption
syndrome, or inability to take oral medication, or have active peptic ulcer disease.

7. Any unstable systemic disease (including active infection, hepatic, renal, metabolic
disease or seizure disorder requiring medication).

8. Significant cardiovascular event: congestive heart failure >NYHA class 2; unstable
angina, active CAD (myocardial infarction more than 1 year prior to study entry is
allowed); serious cardiac arrhythmia requiring anti-arrhythmic therapy ( beta blockers
or digoxin are permitted) or uncontrolled hypertension.

9. Brain metastases or spinal cord compression, if treated before the start of study
treatment, and have any symptoms. Symptoms include signs of increased intracranial
pressure ,headache,nausea and vomiting,cognitive or affective disturbances,seizures,and
focal neurologic symptoms.

10. History of another malignancy within the last 5 years except cured carcinoma in-situ of
uterine cervix, cured basal cell carcinoma of skin and superficial bladder tumors [Ta,
Tis & T1].

11. Pregnant or breast-feeding women.

12. Substance abuse, medical, psychological or social conditions that may interfere with
the patient's participation in the study or evaluation of the study results.

13. Any condition that is unstable or could jeopardize the safety of the patient and their
compliance in the study.