This is a multi-center phase II randomized controlled study to assess the efficacy of
Gefitinib alone and Gefitinib combinating with Pemetrexed/cisplatin on patients with brain
metastasis from non-small cell lung cancer(NSCLC) harboring EGFR mutation type by
intracranial PFS(iPFS),also PFS ,DCR and OS.The side effect is evaluated as well.
1. Patient who was confirmed stage IV NSCLC with EGFR activating mutation and brain
metastases by pathologic histology or cytology
2. Patients who had never received therapy (including chemotherapy,WBRT,EGFR-TKI and EGFR
monoclonal antibody) after diagnosed brain metastases
3. Appraisable disease, the presence of at least three lesions if longest diameter <10 mm
by brain MRI
4. Adult patients (≥ 18 years and ≤75 years). ECOG Performance Status 0 or 1 Life
expectancy of at least 12 weeks.,Haemoglobin ³ 10.0 g/dl, Absolute neutrophil count
(ANC) ³1.5 x 109/L, platelets ³ 100 x 109/L. Total bilirubin £ 1.5 x upper limit of
normal (ULN). ALT and AST < 2.5 x ULN in the absence of liver metastases, or < 5 x ULN
in case of liver metastases. Creatinine clearance ³ 60ml/min (calculated according to
5. Patients should be contraceptive during the period of the trial until 8 weeks after
the last administration of icotinib.
6. Able to comply with the required protocol and follow-up procedures, and able to
receive oral medications.
1. Patient was received irradiation of brain. Patient with meningeal metastases were
confirmed by MRI or cytology test of cerebrospinal fluid.
2. Patient is received the treatment of Phenytoin, carbamazepine, rifampicin,
phenobarbital, or St. John's Wort.
3. Patient was received EGFR Tyrosine Kinase Inhibitor or EGFR monoclonal antibody.
4. Interstitial pneumonia.Pericardial effusion, pleural effusion is uncontrolled .
5. Any unstable systemic disease (including active infection, uncontrolled hypertension,
unstable angina, congestive heart failure, myocardial infarction within the previous
year, serious cardiac arrhythmia requiring medication, hepatic, renal, or metabolic
6. Any significant ophthalmologic abnormality ,especially severe dry eye syndrome
,keratoconjunctivitis sicca,Sjogren syndrome,severe exposure keratitis or any other
disorder likely to increase the risk of corneal epithelial lesions.
7. Lack of physical integrity of the upper gastrointestinal tract, or malabsorption
syndrome, or inability to take oral medication, or have active peptic ulcer disease.
8. The symptoms of increased intracranial pressure are uncontrolled after dehydration and