Apatinib Mesylate Combined With Doxorubicin and Ifosfamide in Advanced Soft-tissue Sarcoma

Inclusion Criteria: 1. Patients voluntarily participated in this study and signed the informed consent; 2. The pathology diagnosed with at least one measurable lesion according to RECIST 1.1 standard. The pathology includes synovial sarcoma, leiomyosarcoma, angiosarcoma, undifferentiated pleomorphic sarcoma/malignant fibrous histiocytoma, liposarcoma, fibrosarcoma, clear cell sarcoma, epithelioid sarcoma, malignant peripheral nerve sheath tumor, undifferentiated sarcoma, rhabdomyosarcoma, dermatofibrosarcoma protuberans, ewing's sarcoma /primary neural ectoderm tumors, desmoplastic small round cell tumor, inflammatory myofibroblastic sarcoma, malignant solitary fibroma. Except for chondrosarcoma, osteosarcoma, malignant mesothelioma, alveolar soft tissue sarcoma, gastrointestinal stromal tumor; 3. Patients with recurrence after surgery or with lymph nodes or distant metastasis after imaging evaluation; 4. 18 \~ 70 years old; ECOG PS score: 0\~1; Expected survival beyond 3 months; 5. Major organs functions should meet the following standards within 7 days before treatment: (1) Blood routine examination standard (without blood transfusion within 14 days) : Hemoglobin (HB) ≥90g/L; The absolute value of neutrophils (ANC) ≥1.5×109/L; Platelet (PLT) ≥80 ×109/L. (2) Biochemical examination shall meet the following standards: Total bilirubin (TBIL) ≤ 1.5 times ULN (Upper Limit Of Normal); alanine aminotransferase （ALT）and aspartate aminotransferase AST≤2.5 times ULN. If accompanied by liver metastasis, ALT and AST≤5 times ULN；Serum creatinine（Cr）≤1.5 times ULN or creatinine clearance rate (CCr)≥ 60ml/min； (3) Doppler ultrasound evaluation: left ventricular ejection fraction (LVEF) ≥ normal low limit (50%). 6\. Women of reproductive age should agree to use contraceptives (such as intrauterine devices, contraceptives or condoms) during and within 6 months after the study; Negative serum or urine pregnancy test within 7 days prior to study enrollment and must be non-lactating; Men should agree to use contraceptives during and within 6 months after the study period. Exclusion Criteria: 1. Patients who have previously used apatinib mesylate; 2. Received any form of chemotherapy after recurrence or metastasis; 3. Patients previously treated with targeted drugs of vascular endothelial growth inhibitors, such as sunitinib, sorafenib, bevacizumab, imatinib, famitinib, pazopanib, regorafenib, and anlotinib. 4. Other malignancies that have occurred or are present at the same time within 5 years, except for cured cancers including carcinoma in situ of the cervix, non-melanoma skin cancer and superficial bladder tumor \[Ta (non-invasive tumor), Tis (carcinoma in situ) and T1 (tumor infiltrating basement membrane)\]; 5. Systemic anti-tumor therapy, including cytotoxic therapy, signal transduction inhibitors, and immunotherapy (or mitomycin C administration within 6 weeks before the treatment with the experimental drug), is planned within 4 weeks before enrollment or during the medication period of this study. In the first 4 weeks of enrollment, the patients were treated with field expanding radiotherapy (ef-rt) or the limited field radiotherapy designed to evaluate tumor lesions in the first 2 weeks of enrollment. 6. Accompanied by pleural effusion or ascites, causing respiratory syndrome (CTCAE grade 2 dyspnea \[grade 2 dyspnea refers to shortness of breath when there is a small amount of activity; it affects instrumental daily life activities\]); 7. Unrelieved toxic reactions caused by any previous treatment higher than CTCAE (4.1) level 1 or above, excluding hair loss; 8. Patients with multiple factors (such as inability to swallow, chronic diarrhea and intestinal obstruction) affecting oral drugs; 9. Patients with brain metastases with symptoms or with symptoms for less than 2 months; 10. Patients with any severe and/or uncontrolled disease, including: 1)Patients with unsatisfactory blood pressure control (systolic blood pressure 150 mmHg, diastolic blood pressure 100 mmHg); 2)Patients with grade I or above myocardial ischemia or myocardial infarction, arrhythmia (including QTC 480ms) and grade II congestive heart failure (NYHA classification); 3)Active or uncontrolled severe infection (CTCAE grade 2 infection); 4)Cirrhosis, decompensated liver disease, active hepatitis or chronic hepatitis require antiviral treatment; 5\) Renal failure requires hemodialysis or peritoneal dialysis; 6\) Have a history of immunodeficiency, including HIV positive or other acquired or congenital immunodeficiency diseases, or have a history of organ transplantation; 7)Poor control of diabetes mellitus (FBG) \> 10mmol/L); 8)Urine routine test indicated urine protein ++, and confirmed the 24-hour urine protein quantitative \> 1.0g; 9)Patients with seizures requiring treatment; 11\. Received major surgical treatment, open biopsy or obvious traumatic injury within 28 days before enrollment; 12\. Patients with any signs of bleeding constitution or medical history, regardless of the severity; Patients with any bleeding or bleeding event CTCAE level 3 within 4 weeks before enrollment have unhealed wounds, ulcers or fractures; 13\. Hyperactive/venous thrombosis events within 6 months, such as cerebrovascular accidents (including temporary ischemic attack), deep venous thrombosis and pulmonary embolism; 14\. Patients with active ulcer, intestinal perforation and intestinal obstruction; 15\. Have a history of mental drug abuse and cannot quit or have mental disorder; 16\. Participated in clinical trials of other anti-tumor drugs within 28 days before enrollment; 17.According to the judgment of the researcher, there are those who seriously endanger the safety of patients or affect the patients' completion of the study.