A Study of Apatinib in Patients With Advanced Non-squamous and Non-small Cell Lung Cancer

Inclusion Criteria:

• ≥ 18 and ≤ 70 years of age
• Histologically or cytologic confirmed advanced non-squamous and non-small cell lung cancer.
• At least one measurable lesion which has not received radiotherapy (larger than 10 mm in diameter by spiral CT scan)
• Have failed for 2 lines of chemotherapy including EGFR-TKI.
• ECOG performance scale 0 - 1.
• Life expectancy of more than 3 months.
• Duration from the last therapy is more than 6 weeks for nitroso or mitomycin
• More than 4 weeks after operation or radiotherapy
• More than 4 weeks for cytotoxic agents or tyrosine kinase inhibitors inhibitors
• Adequate hepatic, renal, heart, and hematologic functions (hemoglobin ≥ 90g/L, platelets ≥ 80×10^9/L, neutrophils ≥ 1.5×10^9/L, total bilirubin within 1.25×the upper limit of normal(ULN), and serum transaminase≤2.5×the ULN (If liver metastases, serum transaminase≤5×the ULN), serum creatine ≤ 1.5 x ULN, creatinine clearance rate ≥ 50ml/min,
• signed and dated informed consent.Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedure.

Exclusion Criteria:

• Squamous cell carcinoma (including adenosquamous carcinoma, undifferentiated carcinoma); small cell lung cancer (including small cell and non-small cell mixed lung cancer)
• Pregnant or breastfeeding women
• Intercurrence with one of the following: hypertension, coronary artery disease, arrhythmia and heart failure
• Any factors that influence the usage of oral administration
• PT, APTT, TT, Fbg abnormal, Receiving the therapy of thrombolysis or anticoagulation.
• Within 4 weeks before the first use of drugs, occurs pulmonary hemorrhage (≥ CTCAE class 2) or other parts' hemorrhage (≥ CTCAE class 3).
• Long-term untreated wounds or fractures.
• Within 6 months before the first treatment occurs artery / venous thromboembolic events, such as cerebral vascular accident (including transient ischemic attack), deep vein thrombosis and pulmonary embolism, etc.
• Application of anticoagulants or vitamin K antagonists such as warfarin, heparin or its analogues; If the prothrombin time international normalized ratio (INR) ≤ 1.5, with the purpose of prevention, the use of small doses of warfarin (1mg orally, once daily) or low-dose aspirin (between 80mg to 100mg daily) is allowed.
• Abuse of alcohol or drugs
• Less than 4 weeks from the last clinical trial
• Treatment with VEGFR, PDGFR, sSRC-TKI before.
• History of any second malignancies within 3 years except cured basal cell carcinoma of skin and carcinoma in-situ of uterine cervix.