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.