Optimizing the Therapeutic Dose of Apatinib Mesylate Tablets in Patients With Lung Cancer by Dose Titration：A Real World Exploratory Study

Exclusion Criteria

• •1. brain MRI, CT or venography confirmed that there are brain hemorrhage symptoms；
• •2. Tumor invade big vessels or close to big vessels (less than 5mm)；
• •3. Patients with uncontrollable hypertension (systolic blood pressure\> 140 mmHg, diastolic blood pressure\> 90 mmHg, despite optimal drug therapy).；
• •4. Patients with with grade Ⅱ myocardial ischemia or myocardial infarction, poor control of arrhythmias (including QTc interval male ≥ 450 ms, female ≥470 ms)；
• •5. Abnormal coagulation (INR\>1.5 or PT\>ULN+4, or APTT\>1.5 ULN), bleeding tendency or receiving coagulation therapy
• •6. Urine protein≥++, or urine protein in 24 hours≥1.0g
• •7. CTCAE 2 degrees or more peripheral neuropathy, except the trauma;
• •8. Unhealed bone fracture or wound for long time；
• •9. Patients who received systemic antibiotic treatment of serious infections;
• •10. Decompensated diabetes or high dose of glucocorticoid treatment other banned disease;
• •11. Patients with active hepatitis B virus or hepatitis c virus infection；
• •12. Patients with obvious factors affecting absorption of oral drugs, such as difficulties in swallowing, chronic diarrhea and intestinal obstruction, etc.
• •13. Received big surgery, had bone fracture or ulcer in 4 weeks.
• •14. Within 6 weeks before random severe weight loss (\> 10%);
• •15. Patients who experienced bleeding symptoms of clinical significance within 3 months before screening, or with confirmed bleeding tendency such as hemorrhage of digestive tract, hemorrhagic gastric ulcer, baseline occult blood in stool ++ and above, or vasculitis, etc；
• •16. Random 12 months before the artery/vein thrombosis events, such as cerebrovascular accident (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism, etc.；
• •17. Known history of hypersensitivity to apatinib or any of it components.