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.