OBJECTIVE Lung cancer is one of the most common cancer in terms of both incidence and mortality in China. In recent years,maintenance chemotherapy after initial induction platium-base doublet in patients with advanced non-small cell lung cancer (NSCLC) has been extensively investigated. However,the optimal maintenance strategy remains controversial. The objective of this retrospective study was designed to assess the efficacy and toxicities of oral etoposide as maintenance therapy for epidermal growth factor receptor (EGFR) mutation-negative advanced NSCLC treated with gemcitabine (GEM) plus cisplatin (DDP) as first-line induction chemotherapy. METHODS From July 2012 to January 2015,a total of 200 chemotherapy-naive advanced NSCLC patients were included at the Department of Medical Oncology,Jiangmen Central Hospital of Sun Yat-Sen University. Eligible patients received induction chemotherapy with GEM at a dose of 1 350 mg/m2,administered intravenously on d1 and DDP at a dose of 25 mg/m2,administered intravenously on d1 to d2. The regimen was repeated every 14 days for a total of six cycles. Each patient received at least 3 cycles of chemotherapy unless there was evidence of disease progression or intolerance of the study treatment. Tumor response rate was evaluated with computed tomography scanning (CT scan) according to RECIST criteria at the third and sixth cycles,respectively. A total of 115 non-progressive patients following 6 cycles of induction chemotherapy were assigned to observation or oral etoposide group according to 1:1. All patients were informed consents. Fifty-five patients in the group A were observed,while sixty patients in group B received switch maintenance treatment with oral etoposide at a dose of 25 mg daily for 14 days,repeated every 21 days. All patients were accessed every 2 months by CT scan. RESULTS All of 200 patients were evaluated. The median follow-up time was 16.8 months. For 200 patients,the rate of objective response disease control rate was 28.0%(56/200) and 57.5%(115/200),respectively,and the median progression free survival (PFS) was 5.4 months. The PFS was 8.2 months in 115 patients who achieved stable or better following induction chemotherapy. Patients in the Group B experienced significant improvements in PFS (9.0 vs 7.8 months,χ2=4.971,P=0.027) compared with patients in the Group A. The grade Ⅰ to Ⅱ leukopenia,thrombocytopenia and anemia in both groups were not significantly different (P>0.05). A statistically significant difference was noted in the incidence of nausea and vomiting between the group A and group B (20.0% vs 36.7%,χ2=3.896,P=0.048). CONCLUSIONS Switch maintenance therapy with oral etoposide may improve FPS in EGFR mutation-negative advanced NSCLC patients,with well-tolerated toxicity profile. These findings require further investigation. © 2017, Editorial Board of Chinese Journal of Cancer Prevention and Treatment. All right reserved.