Gemcitabine and Cisplatin With/Without Anlotinib in Advanced Nasopharyngeal Carcinoma

Inclusion Criteria: 1. Informed of the investigational nature of this study and give written informed consent 2. Histologically or cytologically confirmed nasopharyngeal carcinoma, tumor staged as IVB (according to the 8th AJCC edition) or recurrent tumor nott suitable for local treatment. 3. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 to1, life expectancy of at least 12 weeks. 4. Antitumor therapy naive for recurrent or metastatic nasopharyngeal carcinoma 5. Completed radiotherapy for local tumor 4 weeks before the enrollment 6. Measurable disease other than brain metastasis based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 7. Adequate organ system function, defined as follows: 1. ANC ≥1.5×109/L, PLT ≥100×109/L, Hb）≥90g /L; 2. TBIL ≤ 1.5×ULN；Aminopherases (ALT and AST) ≤ 2.5 × ULN (without liver metastasis) or ≤ 5.0 × ULN (with liver metastasis), Creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 50 ml/min; 3. Urine protein \< ++，or urine protein ≥ ++ concomitant with content of -hour urinary protein \<1.0 g; 4. INR≤1.5×ULN, APTT≤1.5×ULN; 5. LVEF ≥50%; 8. Women who are not of child-bearing potential, and women of child-bearing potential who have a negative serum or urine pregnancy test prior to initial trial treatment, and who agree to use adequate contraceptive measures during the study; Men with partners of childbearing potential willing to use adequate contraceptive measures during the study Exclusion Criteria: 1. Patients with a previous malignancy within the past 5 years (other than curatively treated in situ carcinoma of the cervix, non-melanoma skin cancer and superficial bladder carcinoma). 2. Allergic to anotinib or the chemotherapeutic agents involved in this trial; 3. Supposed to receive locally treatment (except for those with symptomatic bone metastases receive appropriate local doses radiotherapy which does not affect the hemogram) 4. Patients that have received definitive radiotherapy, adjuvant chemotherapy or cocurrent chemoradiotherapy for stage I-IVA and developed recurrent disease within 6 months; 5. Patients that have previously received target therapies; 6. Patients that have previously received immunotherapy (i.e.,interferon, or IL-2 ) 28 days before randomization or within 5 half-life of the drug. 7. Patients that have previously received immunosupressive drugs (i.e., Corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide or TNF-α) 8. Symptomatic CNS metastasis (i.e. encephaledema, hormone intervention, or brain metastasis progression) 9. Patients currently have bleeding tendency, including but not limited to gastrointestinal bleeding, nasal bleeding, hemoptysis, and persistent bleeding or coagulopathy; 10. Hemoptysis (defined as coughing out or spitting out ≥ 1 teaspoon of blood or small blood clots or hemoptysis without sputum) within 28 days before randomization, not including bloody sputum. 11. Radiograph (within 28 days before randomization) showed that the tumor surrounded important blood vessels, and the investigators determined that entering the study would cause bleeding risk; 12. Subjects have any of the following severe acute complications: 1. Unstable angina and/or congestive heart failure or vascular disease (eg, aortic aneurysm requires surgically repaired or peripheral venous thromboembolism) requiring hospitalization within 12 months, or other cardiac impairments (eg,uncontrolled arrhythmias) determined by the investigator, which may affect the evaluation of drug safety; Myocardial infarction or ischemia with ST elevation ≥ 2 mm indicated by ECG; 2. Arterial thromboembolism, venous thromboembolism in grade 3 or higher (according to NCI-CTCAE), transient ischemic attack (TIA), cerebral vascular accident (CVA), transmural myocardial infarction ( MI), hypertensive crisis or hypertensive encephalopathy within 24weeks; 3. Chronic Obstructive Pulmonary Disease (COPD) or other respiratory diseases requiring hospitalization within 28 days before randomization; 4. Abdominal fistula, gastrointestinal perforation, intra-abdominal abscess, or acute gastrointestinal bleeding within 24 weeks before randomization; 5. Esophageal and gastric varices, unhealed ulcers, unhealed wounds or fracture within 24 weeks before randomization; 6. Pulmonary infections and/or acute bacterial or fungal infections requiring intravenous antibiotic therapy 7. Clinical jaundice and/or coagulation disorders caused by liver dysfunction; 8. Minor surgical procedures (including catheterization, excluding peripheral venipuncture central vena catheterization) within 2 days of randomization; 13. The virological test indicates that either of the following 28 days before randomization 1. HBsAg positive and HBV DNA ≥ 1 × 103 copies/L; 2. Anti-HCV positive 3. HIV positive 14. Participation of an anti-tumor clinic trial within 28 days before randomization