The Clinical Study And The Mechanism On The Reversion Of Acquired Resistance With The First Generation EGRF-TKIs For Advanced NSCLC Patients

Objective:To observe the efficacy and safety of thalidomide for advanced non-small cell lung cancer patients with acquired resistance to first generation epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs)and discuss the relations with serum concentration ofbFGF and VEGF.Method:52 cases of non-small cell lung cancer patients with drug resistance to first generation EGFR-TKIs were recruited in this study from January 1~stt of 2010 to December31st of 2015 in the Department of Oncology,Huangshan City People's Hospital.Thalidomide was added to TKI treatment of patients with disease progression after a first generation TKI.An hour before bedtime,100mg thalidomide was taken by patients.The dose increased from 50 mg every3 days and the maximum dose was 300 mg.The efficacy,toxicity and survival of patients wereanalyzed.The serum concentration of bFGF and VEGF before Thalidomide given and afterfailure of combined therapy of Thalidomide with TKIs were detected.Result:In all patients,the partial response(PR)and stability of disease(SD)were 4 cases and 16 cases,and the effective rate was 7.7%,the disease control rates was 38.5%.There was no serious adverse reaction in all patients.After treatment,the progress free survival(PFS)was from 3 weeks to 44 weeks,and the median PFS was 7 weeks.The overall survival(OS)was from 52 weeks to 240 weeks,and the median OS was 108 weeks.According to the comparison of group by the gender and the PFSlonger than 44 weeks after a first generation TKI treatment,the PFS after combination therapy had statistical significance(P<0.05).Conclusion:Thalidomide might be helpful to the reversal of first generation TKI resistance.For female patients and patients with a longer time to progression in non-small cell lung cancer,it was beneficial at a certain significance.A randomized controlled study is warranted to confirm the efficacy of thalidomide.Thalidomide reverse the first generation TKI resistance may be through bFGF and VEGF.