Retreatment With Tyrosine Kinase Inhibitor After Resistance Of Gefitinib Treatment In Advanced Non-small Cell Lung Cancer

Objective: Targeted drugs, epidermal growth factor receptor tyrosine kinaseinhibitors (EGFR-TKIs), have brought great survival benefit for some patients withnon-small cell lung cancer (NSCLC). However, currently there is still no standardtreatment after failure due to secondary resistance. Whether EGFR-TKIs could be usedagain is the focus of current research. This paper is designed to retrospectively study theretreatment with TKI after secondary resistance of gefitinib treatment in AdvancedNSCLC and explore clinical factors associated with the response to retreatment withTKI.Methods: Collected from July2007to February2013in our hospital,88NSCLCpatients who previously received gefitinib treatment were histologically or cytologicallydiagnosed as NSCLC and confirmed to be locally advanced or metastatic (IIIb or IVstage) by pathology or imaging, ECOG score of0to2, and there was at least ameasurable lesion according to RECIST Response Evaluation Criteria.47cases ofpatients with secondary resistance received TKI retreatment during some period afterprogression. Among47cases of drug-resistant patients,34patients receivedchemotherapy between initial and retreatment TKI,7resistant patients maintainedgefitinib original amount therapy combined with local treatment, and6patients receivedthe gefitinib increased the amount of therapy. Responses were evaluated by CT scan thefirst month after the first treatment and thereafter every two months. Evaluate theresponses in accordance with the efficacy evaluation criteria of Solid Tumors, RECIST1.0. The adverse events were classified according to NCICTC2.0.Results: For88cases of patients with initial gefitinib treatment, median progression-free survival (PFS) was22months and median overall survival was43months. As to47cases of patients with secondary resistance, the median PFS of initialgefitinib treatment was13months and median OS was35months, while median PFS ofTKI retreatment was2.5months and median OS was10months. For responses to initialgefitinib treatment in47resistant patients, it was observed that complete response (CR)was0patients, partial response (PR) was10cases (21.3%), stable disease (SD) was36cases (76.6%), progressive disease (PD) was1case (2.1%), response rate (RR) was21.3%and disease control rate (DCR) was97.9%. For responses to TKI retreatment in47resistant patients, it was observed that CR or PR was0patients, SD was22cases(46.8%), PD was25case (53.2%), RR was0and DCR was46.8%. Clinicalcharacteristics (gender, histological type, smoking history, age, clinical stage andECOG score) and treatment characteristics (efficacy of initial gefitinib treatment, PFSlength of initial gefitinib therapy, initial gefitinib medication timing between the twoTKI interval, chemotherapy during the two TKI interval, increased the amount ofretreatment TKI) had no statistic influence on PFS of retreatment TKI in47cases ofdrug-resistant patients. There were no significant statistic differences among PFS ofretreatment TKI in3subsequent treatment programs after secondary resistance. Thetoxicities associated with the2ndTKI therapy were generally acceptable.Conclusion:1. Retreatment TKI after secondary resistance in patients with the effective initialgefitinib treatment can still make some patients achieved clinical benefit.2. Clinical characteristics and treatment characteristics of resistant patients had nosignificant effect on the efficacy of retreatment TKI.3. The follow-up treatment of secondary resistance patients can selectindividualized treatment plan based on the patient’s previous treatment, the speed of thediseases’ progression, ECOG score and so on. The specific three treatment programs areas follows:A. Patients with rapid speed of the progressive disease, initial gefitinib as first-lineor second-line treatment and ECOG score0-2can consider sequential chemotherapyand retreatment TKI.B. Patients with stable intrapulmonary primary lesions, progression or occurrenceof metastases can consider original dose of gefitinib therapy combined with topicaltreatment.C. Patients who can not tolerate chemotherapy with slow speed of the progressive disease can consider high dose of gefitinib treatment.