1. Compare the effect and safety of gefitinib alone with gefitinib plus concomitant WBRT(whole-brain radiotherapy ) in treatment of NSCLC patients harboring an EGFR mutation with multiple BM. 2. Verify the failure pattern of NSCLC patients harboring an EGFR mutation with multiple BM. 3. Explore the rescuable therapy after progression of disease.
Name: Gefitinib
Name: WBRT
Description: Compare the progression free survival(PFS) and safety in two arms,including intracranial PFS、extracranial PFS and overall PFS.
Measure: Time to progression Time: 12-14 monthsDescription: intracranial or extracranial site
Measure: Disease Progression Classification Time: 3 yearsDescription: measured by ECGO(Eastern Cooperative Oncology Group) PS (Performance Status)
Measure: Health-related quality of life Time: 3 yearsDescription: measured by scale of MMSE( Mini Mental Status Examination)
Measure: Mental Status Time: 3 yearsAllocation: Randomized
Parallel Assignment
There is one SNP
Inclusion Criteria: - years of age or older - ECOG score ≤ 2 - Recursive Partitioning Analysis(RPA) Class I-II; - The pathological diagnosis of primary non-small cell lung cancer and detection of pulmonary primary ARMs; - Sequencing EGFR mutation(primary lesion or metastases,exon 19 deletions or exon 21 L858R (EGFR mutation in exon 21, L858R point mutation) mutations; - Enhanced MRI showed brain metastases ≥ 4; - 1 or 2 line treatment revealed failure; - No use of EGFR-TKIs(Tyrosine kinase inhibitors) previously; - No treatment for BM previously,including WBRT, SRS, surgery or experimental therapy; - Expected survival period over 3 months; - Two weeks before randomization, organs function in patients with meet the following criteria: - bone marrow:HB(hemoglobin) ≥ 90g/L, neutrophil≥ 1.5 × 109/L and platelet ≥ 100 × 109/L; - liver function:total bilirubin ≤ 1.5 times the upper limit of normal, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 times the upper limit of normal; - renal function:more than 1.5 times the upper limit of normal serum creatinine or creatinine clearance rate ≥ 60 ml/min; - Urine dipstick testing the proteinuria < 1+; if the urine dipstick test value, 1+, is 24 hours total urine protein must < 500mg; - blood glucose:normal range,DM(diabetes mellitus) patients are under treatment and have a stable state; - Can understand and consent Exclusion Criteria: - Patients have been treated with brain radiation or surgery of BM; - Prior of EGFR-TKIs; - Mixed with small cell lung cancer patients with components; - Wild-type of EGFR; - Unable to tolerate MRI scanning; - Post 2 line treated patients; - Brain meninges metastases or incorporate with brain meninges metastases; - 5 years before other cancers except NSCLC treatment in patients with the start of the study (except for simple operation resection and there are at least 5 consecutive years disease free survival, has been cured of cervical carcinoma in situ, has cured the base cell cancer and bladder epithelial tumor); - Before entering the group 4 weeks received any other investigational drugs; - Incorporate with local symptoms(hemiplegic paralysis, anepia, nystagmus, ataxia.et); --- L858R ---
Inclusion Criteria: - years of age or older - ECOG score ≤ 2 - Recursive Partitioning Analysis(RPA) Class I-II; - The pathological diagnosis of primary non-small cell lung cancer and detection of pulmonary primary ARMs; - Sequencing EGFR mutation(primary lesion or metastases,exon 19 deletions or exon 21 L858R (EGFR mutation in exon 21, L858R point mutation) mutations; - Enhanced MRI showed brain metastases ≥ 4; - 1 or 2 line treatment revealed failure; - No use of EGFR-TKIs(Tyrosine kinase inhibitors) previously; - No treatment for BM previously,including WBRT, SRS, surgery or experimental therapy; - Expected survival period over 3 months; - Two weeks before randomization, organs function in patients with meet the following criteria: - bone marrow:HB(hemoglobin) ≥ 90g/L, neutrophil≥ 1.5 × 109/L and platelet ≥ 100 × 109/L; - liver function:total bilirubin ≤ 1.5 times the upper limit of normal, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 times the upper limit of normal; - renal function:more than 1.5 times the upper limit of normal serum creatinine or creatinine clearance rate ≥ 60 ml/min; - Urine dipstick testing the proteinuria < 1+; if the urine dipstick test value, 1+, is 24 hours total urine protein must < 500mg; - blood glucose:normal range,DM(diabetes mellitus) patients are under treatment and have a stable state; - Can understand and consent Exclusion Criteria: - Patients have been treated with brain radiation or surgery of BM; - Prior of EGFR-TKIs; - Mixed with small cell lung cancer patients with components; - Wild-type of EGFR; - Unable to tolerate MRI scanning; - Post 2 line treated patients; - Brain meninges metastases or incorporate with brain meninges metastases; - 5 years before other cancers except NSCLC treatment in patients with the start of the study (except for simple operation resection and there are at least 5 consecutive years disease free survival, has been cured of cervical carcinoma in situ, has cured the base cell cancer and bladder epithelial tumor); - Before entering the group 4 weeks received any other investigational drugs; - Incorporate with local symptoms(hemiplegic paralysis, anepia, nystagmus, ataxia.et); --- L858R --- --- L858R ---