The development of anti-angiogenesis drugs has led to renewed enthusiasm in lung cancer treatments. Apatinib is a tyrosine kinase inhibitor which selectively inhibits the vascular endothelial growth factor receptor-2 (VEGFR-2). Etoposide is an oral preparation for lung cancer which is recommended by NCCN guideline. The investigators wondered whether these two drugs have synergistic effects when treating advanced non-small cell lung cancer patients who failed to previous at least 2nd line treatments. Thus, the aim of this trial is to investigate the efficacy and safety of apatinib combined with etoposide in heavily pretreated advanced non-small cell lung cancer.

Inclusion Criteria:

• Obtain of informed consent.

• Histologically or cytologically confirmed non-small cell lung cancer.

• World Health Organization (WHO) performance status (PS) of 0 to 2.

• Measurable lesions as defined by RECIST criteria.

• Second-line or more treatments.

• Wild type of epidermal-growth-factor receptor (EGFR).

• Life expectancy ≥12 weeks.

• Organ functions normal, as defined below, within two weeks of randomization:

  • Hb≥90g/L Absolute neutrophils count(ANC)≥1.5×109/L Platelets≥80×109/L Serum bilirubin≤2×ULN; Aspartate transaminase(AST) and alanine transaminase (ALT)≤2.5×ULN(≤5×ULN if liver metastases) Creatinine clearance≥45ml/min or Cr≤1.25×ULN.

• Females of child-bearing potential must have negative serum pregnancy test.

• Sexually active males and females (of childbearing potential) willing to practice contraception during the study.

Exclusion Criteria:

• Small cell lung cancer.
• Newly diagnosed Central Nervous System (CNS) metastases that have not yet been definitively treated with surgery and/or radiation.
• Uncontrolled hypertension.
• Myocardial ischemia or infarction more than stage II, cardiac insufficiency.
• Abnormal coagulation (INR>1.5 or PT>ULN+4, or APTT>1.5 ULN), bleeding tendency or receiving coagulation therapy.
• Difficulties in taking pills (inability to swallow tablets,GI tract resection, chronic bacillary diarrhea and intestinal obstruction).
• Hemoptysis, more than 2.5ml daily.
• Thrombosis in 12 months, including pulmonary thrombosis, stoke, or deep venous thrombosis.
• Unhealed bone fracture or wound for long time.
• Received big surgery, had bone fracture or ulcer in 4 weeks.
• Urine protein≥++, or urine protein in 24 hours≥1.0g.
• Pregnant or lactating woman.