the purpose of this study is to evaluate the efficacy and safety of high-dose，pulsatile Erlotinib/Gefitinib in advanced non small cell lung cancer (NSCLC) patients after failure of standard dose EGFR-TKIs（Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors）

To evaluate the efficacy and safety by treating the advanced non small cell lung cancer (NSCLC) patients who have failure of standard dose EGFR-TKIs(Erlotinib or Gefitinib ) with high-dose, pulsatile Erlotinib(450mg every 3 days) or Gefitinib (1000mg every 4 days)

Inclusion Criteria:

• 1. NSCLC patients were confirmed by histology or cytology 2. Patients were ever treated with standard dose EGFR-TKIs(Erlotinib or Gefitinib )on which he/she achieved complete remission/partial remission,or maintained stable disease for 4 months.Disease progression at present (accord to RECISTv1.1 criteria） 3.At least one target lesion that has not previously been radiated and is measurable according to RECIST v1.1; 4.Have an ECOG PS of 0-2 5.At least 8 weeks of expected survival time 6.Have no serious cardiovascular,hepatobiliary or renal disorders 7.Provision of a voluntarily given, personally signed and dated, written informed consent document 8.Must be in accordance with the following laboratory biochemical data: Hgb≥80g/L，WBC≥3.0×10^9/L，ANC≥1.0×10^9/L， PLT≥80×10^9/L Renal function：SCr≤ULN Liver function： if no hepatic metastases:AST/ALT≤2.5ULN if hepatic metastases:AST/ALT≤5ULN

Exclusion Criteria:

• If the subject meet any of the following exclusion criteria ,he/she is no eligible to participate in this study

  1. Have chronic toxicity reaction(above grade 2) and not recovered( hair loss not include)
  2. Have Appeared skin rashes or diarrhea(above grade 3),or have any reason lead to decrement during standard dose EGFR-TKIs treatment
  3. Female subjects who are in pregnancy or lactation，or of childbearing age but don't take any contraceptive measures
  4. Current enrollment in another therapeutic clinical study
  5. Have any symptoms of brain metastases or leptomeningeal metastases
  6. Subjects will not be eligible if they have history of prior malignancy in past 5 years
  7. Any psychiatric or cognitive disorder that would limit the understanding or rendering of informed consent and/or compromise compliance with the requirements of this study or known drug abuse/alcohol abuse.