Apapitatin Combined With SOX for Palliative Adjuvant Chemotherapy in Patients With Advanced Gallbladder Carcinoma

Inclusion Criteria:

1. ages 18 to 75
2. UICC/AJCC gallbladder TNM staging (The eighth edition), Ⅲ B - ⅣB (excluding M1) postoperative pathological diagnosis of gallbladder carcinoma;Patients confirmed to have undergone R1/R2 cholecystectomy or palliative surgery;
3. The primary treatment is surgical resection or potentially resectable cholecystic carcinoma without other treatment
4. ECOG performance status ≤1
5. The liver and kidney function meets the following conditions： BIL\<3 normal value upper limit (ULN)；ALT and AST\< 2.5 xULN;Serum Cr≤ 1xULN,Clearance rate of endogenous creatinine\>50ml/min（Cockcroft-Gault）;
6. Other test rooms meet the following requirements:

   Hemoglobin ≥ 90 g/L (no blood transfusion within 14 days)；Neutrophilic granulocyte count \> 1.5x109 /L;The platelet count ≥ 80 x 10 \^ 9/L;
7. Estimated life expectancy \> 3 months.
8. Before the enrollment, the heart function is good. There is no episode of myocardial infarction within half a year. For example, if you have hypertension or coronary heart disease, you should ensure that it is within the controllable range.
9. Patient able and willing to provide written informed consent and to comply with the study protocol and Good compliance, with follow-up.

Exclusion Criteria:

1. Non gallbladder carcinoma
2. Significant clinical bleeding symptoms or a clear tendency to bleed occurred within the first month of randomization, such as cough/hemoptysis of 2.5ml or more, gastrointestinal bleeding, esophagogastric varices at risk of bleeding, hemorrhagic gastric ulcer, etc.
3. Other topical treatments during the study (including intraperitoneal chemotherapy, radiotherapy, etc.)
4. Pregnant or lactating women；
5. Those who suffer from high blood pressure and cannot be treated to the normal range by antihypertensive drugs；
6. HIV infection or the presence of AIDS-related diseases, or severe acute and chronic diseases;
7. Have grade II or higher myocardial ischemia or myocardial infarction、Poorly controlled arrhythmia；
8. Severe active infections；
9. There are secondary malignant tumors or other tumors within 3 years before the start of the study and there is metastasis of the brain or meninges.
10. Researchers believe that their compliance is poor
11. There are contraindications for Apatinib and S-1