Apatinib and Irinotecan Combination Treatment in Unresectable or Metastatic Esophageal Squamous Cell Carcinoma

Inclusion Criteria: * Age 18 to 70 years. Both genders are eligible. * Patients must have histologically confirmed esophageal squamous cell carcinoma with unresectable or metastatic disease. * With measurable or evaluable disease defined by RECIST 1.1 criteria by multi-slice spiral CT or MR scan. * Failed in or disease progressed after fist-line chemotherapy (A. If failed in preoperative chemotherapy / chemoradiotherapy or disease progressed in 24 weeks after esophagectomy, the preoperative chemotherapy/ chemoradiotherapy is regard as first-line chemotherapy. B. If failed in definitive chemoradiotherapy or disease progressed in 24 weeks after definitive chemoradiotherapy, the definitive chemoradiotherapy is regard as first-line chemotherapy; C. If failed in or relapse in 24 weeks after adjuvant chemotherapy, the adjuvant chemotherapy is regard as first line chemotherapy). * Patients must have a performance status of 0-2 on the ECOG scale. * Life expectancy ≥3 months. * With normal marrow, liver and renal function:a hemoglobin (HGB) of ≥110g/L (without blood transfusion during 14 days); a neutrophil count of ≥2.0×109/L; a platelet count of ≥100×109/L; a total bilirubin (TBil) of ≤1.5 upper normal limitation (UNL) or ≤3 UNL in case of liver metastasis. a creatinine (Cr) of ≤ 1.5 UNL or a creatinine clearance rate ≥ 50ml/min (Cockcroft-Gault); a alanine aminotransferase (ALAT) and aspartate aminotransferase (ASAT) of ≤2.5 UNL or ≤5 UNL in case of liver metastasis. Fecal occult blood (-); Urine test: protein\<(++) or \<1.0g per 24 hours. * Without bleeding and thrombosis disease. * With normal coagulation function: APTT, PT and INR, each ≤ 1.5 ULN * With normal electrocardiogram results and no history of congestive heart failure. * Female subjects of child-bearing potential must agree to use contraceptive measures starting 1 week before the administration of the first dose of apatinib until 8 weeks after discontinuing study drug. Male subjects must agree to use contraceptive measures during the study and 8 weeks after last dose of study drug. * With good compliance and agree to accept follow-up of disease progression and adverse events. * With written informed consent signed voluntarily by patients themselves or their supervisors witted by doctors. Exclusion Criteria: * Patients who have received irinotecan or apatinib in previous treatment. * Other pathological type cancers of esophagus except for squamous cell carcinoma * Uncontrolled hypertension (Treatment of antihypertensive drugs cannot reduced to the normal range: systolic pressure ≤140 mmHg and diastolic pressure ≤90 mmHg) * With ≥grade 2 coronary heart disease, arrhythmia (including QTc interval prolongation male \>450 ms, women \>470 ms) * Cannot take oral tables including uncontrolled vomiting, chronic diarrhea and intestinal obstruction. * With potential bleeding risk of GI including (1) peptic ulcer and fecal occult blood (++ - +++); (2) melena or hematemesis history in last 3 months;(3) In case of fecal occult blood (+) or (+/-),fecal occult blood examination must be repeat in one week. If fecal occult blood is still (+) or (+/-),endoscopy is required and if there are ulcer or other diseases with bleeding risk in the opinion of the investigators. (4) Primary tumour lesion is of deep ulcer and in the opinion of the investigators may place the patient at risk of fetal bleeding or GI perforation. * Urine test: protein\>(++) or \>1.0g per 24 hours. * With abnormal coagulation function (INR\>1.5 ULN, APTT\>1.5 ULN), * With thrombosis or receiving anticoagulant treatment. * With serious diseases such as congestive heart failure, uncontrolled myocardial infarction and arrhythmia, liver failure and renal failure. * With brain metastasis * Pregnant or lactated women.