Apatinib Mesylate Combined With Pemetrexed in the Treatment of Pretreated Advanced Non-squamous Non-small Cell Lung Cancer

Inclusion Criteria:

1. Aged from 18 years to 70years.
2. Histologically or cytologically confirmed non-squamous non-small cell lung cancer(stage IIIB/IV).
3. Measurable lesions as defined by RECIST criteria.
4. Locally advanced lung cancer cannot treat with surgery, recurrent or metastatic lung cancer
5. ECOG performance status (PS) of 0 to 1.
6. Life expectancy ≥3 months.
7. Informed consent.

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. The active HBV or HCV infection
9. History of other malignancies except cured basal cell carcinoma of skin and carcinoma in-situ of uterine cervix.
10. Hemoptysis, more than 2.5ml daily
11. Thrombosis in 12 months, including pulmonary thrombosis, stoke, or deep venous thrombosis.
12. Unhealed bone fracture or wound for long time
13. Received big surgery, had bone fracture or ulcer in 4 weeks.
14. Urine protein≥++, or urine protein in 24 hours≥1.0g
15. Use of CYP3A4 inhibitor within 7 days or CYP3A4 inducer within 12 days prior to enrollment
16. Have received prior treatment with VEGFR TKI (Bevacizumab is permitted).
17. Pregnant or lactating woman, or woman unwilling to practice contraception during the study.