Anlotinib Combined With Dose-dense Temozolomide for the First Recurrent or Progressive Glioblastoma After STUPP Regimen

Inclusion Criteria:

1. The primary tumor must be pathologically confirmed as supratentorial glioblastoma;

2. The primary tumor progressed or relapsed for the first time after surgery (includingbiopsy, partial resection, total resection), standard radiotherapy and temozolomideconcurrent chemotherapy and temozolomide adjuvant chemotherapy (STUPP regimen),including multiple intracranial recurrence and new lesions.;

3. Age ≥ 18 years old,≤75 years old;

4. KPS ≥ 60;

5. the expected survival time is more than 12 weeks;

6. within 28 days before entering the group, patients need to undergo craniocerebralenhanced MRI, and the lesions on MRI must be measurable;

7. for patients undergoing the second surgery after the first recurrence, baseline MRIshould be obtained at least 4 weeks after operation;

8. if the patient is undergoing hormone therapy, the hormone dose must be stable orreduced at least 5 days before baseline MRI;

9. For patients undergoing re-radiation therapy, the baseline MRI should be obtained atleast 8 weeks or 4 weeks after the end of the radiotherapy (the recurrence lesion isnot in the radiation field);

10. For patients who are treated with gamma knife or other hyperdivision methods for thefirst time, Recurrence or progression must be confirmed by pathology (except forpatients with new lesions);

11. Peripheral blood picture, liver and kidney function, etc. are within the followingallowable range (detected within 7 days before the start of treatment): neutrophils (ANC) ≥ 1.5×109/L; hemoglobin (HGB) ≥100g/L; platelets (PLT) ≥100×109/L; livertransaminase (AST/ALT) ≤2.5 times the upper limit of the normal range; total bilirubin (TBIL) <1.5 times the upper limit of the normal range; Creatinine (CREAT) <1.2 timesthe upper limit of the normal range; International normalized ratio (INR) <1.5;Activated partial thromboplastin time (APTT) <1.5 times the upper limit of the normalrange (except for patients receiving anticoagulation therapy); Urinary protein (PRO)/creatinine (CRE) ratio ≤1.0;

12. The patient must have fully recovered from the toxicity of previous chemotherapy ortargeted therapy, and at least 30 days from the last treatment; 13.Before startingtreatment, the patient must Complete recovery from surgery, postoperative infection orother comorbidities;

14.Patients of childbearing age (including female and male patients' female partners) musttake effective birth control measures; 15.Sign informed consent.

Exclusion Criteria:

• 1.Patients who have participated in other clinical trials in the past and have notterminated the trial; 2.Patients who have used Anlotinib in the past; 3. Baseline MRIsuggests the recent risk of cerebral hemorrhage or brain herniation; 4. Pregnant orbreast-feeding women; 5.Those who are difficult to control acute infections; 6. Peoplewho take drugs, drug abuse, long-term alcoholism and AIDS; 7.Have frequent vomiting orhave conditions that affect the oral administration of drugs; 8. Hypertension thatcannot be controlled by drugs The patient (>150/100mmHg); 9. Previous hypertensiveencephalopathy; 10. Hemorrhage tendency or coagulopathy; 11. Thrombolytic oranticoagulant therapy (unless low molecular weight heparin or warfarin is used); 12).≥Grade 2 cardiac insufficiency (NYHA criteria) or congestive heart failure; 13. Pasthistory of myocardial infarction or unstable angina, stroke and transient ischemicattack within 6 months; 14. Serious vascular disease; 15.Peripheral artery embolismoccurred recently; 16. Abdominal fistula, gastrointestinal perforation and abdominalabscess occurred in the past; 17.Intracranial abscess occurred within 6 months; 18.Major surgery, open biopsy or Have suffered major trauma; 19. Those who are expectedto undergo major surgery; 20).Those who have severe incurable wounds, ulcers orfractures; 21).Those with a history of pulmonary fibrosis, interstitial pneumonia,pneumoconiosis, radiation pneumonia, drug-related pneumonia, severely impaired lungfunction, etc.; 22.patients who are allergic to known ingredients of Anlotinib; 23.There is a serious skin disease; 24. Other concomitant diseases that seriouslyendanger the safety of patients or affect the completion of the study according to thejudgment of the investigator .