The Efficacy and Safety of Apatinib in Heavily Pretreated Advanced Non-squamous Non-small Cell Lung Cancer

Inclusion Criteria:

1. Obtain of informed consent.
2. Aged 18 years and over.
3. Histologically or cytologically confirmed non-squamous non-small cell lung cancer.
4. World Health Organization (WHO) performance status (PS) of 0 to 2.
5. Measurable lesions as defined by RECIST criteria.
6. Life expectancy ≥12 weeks.
7. Progressed after at least two lines systemic treatment, or were not amendable to receive the current standard therapy

7. 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 8. 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:

1. Squamous carcinoma (including adeno-squamous carcinoma), small cell lung cancer.
2. Newly diagnosed Central Nervous System (CNS) metastases that have not yet been definitively treated with surgery and/or radiation.
3. Tumor invade big vessels or close to big vessels (less than 5mm)
4. Obvious cavity or necrosis formed in the tumor
5. Uncontrolled hypertension
6. Myocardial ischemia or infarction more than stage II, cardiac insufficiency.
7. Abnormal coagulation (INR>1.5 or PT>ULN+4, or APTT>1.5 ULN), bleeding tendency or receiving coagulation therapy
8. Hemoptysis, more than 2.5ml daily
9. Thrombosis in 12 months, including pulmonary thrombosis, stoke, or deep venous thrombosis.
10. Unhealed bone fracture or wound for long time
11. Received big surgery, had bone fracture or ulcer in 4 weeks.
12. Urine protein≥++, or urine protein in 24 hours≥1.0g
13. Pregnant or lactating woman.