Effect of Bevacizumab on Radiation-induced Brain Necrosis in Patients With Nasopharyngeal Carcinoma
Condition: Nasopharyngeal Carcinoma; Adverse Effect of Radiation Therapy; Brain Necrosis
MeSH terms: Carcinoma; Nasopharyngeal Carcinoma; Necrosis
Intervention: bevacizumab; Corticosteroid
Intervention description: Patients receive bevacizumab 5mg/kg intravenously over 30-90 minutes on day1. Treatment repeats every 2 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.; Patients in the corticosteroid group were treated with intravenous pulsed-steroid therapy: methylprednisolone 500 mg daily intravenously for three consecutive days followed by oral prednisone 60 mg for five days and gradually tapered 15mg every 5 days. When the prednisone dose reached 30mg per day, it was tapered down more slowly (tapered 5mg every week), until a maintenance dose of 10mg per day was reached. The entire intervention lasted two months. At 2 months, prednisone was stopped.
Intervention MeSH terms: Methylprednisolone; Bevacizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Enrollment: 112.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: radiation-induced brain necrosis; nasopharyngeal carcinoma; Bevacizumab; Methylprednisolone

Summary:

      Bevacizumab may have a better effect on brain necrosis caused by radiotherapy.This randomized
      trial aims to investigate whether bevacizumab may alleviate radiation-induced brain necrosis
      in patients with nasopharyngeal carcinoma. The effect will be compared with outcomes in
      patients receiving steroid therapy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have received radiotherapy for histologically confirmed nasopharyngeal
             carcinoma.

          -  Prior irradiation >/= 6 months prior to study entry.

          -  Radiographic evidence to support the diagnosis of radiation-induced brain necrosis
             without tumor recurrence.

          -  Age>/= 18 years. Because on dosing or adverse event data are currently not available
             on the use of bevacizumab in patients <18years old.

          -  No prior bevacizumab therapy.

          -  No evidence of very high intracranial pressure that suggests brain hernia and needs
             surgery.

          -  Fertile women who are willing to take contraception during the trial.

          -  Routine laboratory studies with bilirubin </=upper limits of normal (ULN), aspartate
             aminotransferase (AST or SGOT) < ULN, creatinine <ULN, red-cell count >/= 4,000 per
             cubic millimeter; white-cell count >/=1500 per cubic millimeter, platelets >/= 75,000
             per cubic millimeter; Hb >/=9.0. PT, APTT, INR in a normal range.

          -  If with history of seizures, patients should be on anticonvulsant therapy. However,
             preference will be enzyme-non-inducing anticonvulsants.

          -  Ability to understand and willingness to sign a written informed consent document.

          -  The patient has no active bleeding or pathological condition that carries a high risk
             of bleeding; there is no evidence of serious or non-healing wound, ulcer or bone
             fracture.

        Exclusion Criteria:

          -  Patients with any of the following should be excluded: 1) evidence of metastatic
             disease; 2)evidence of tumor invasion to major vessels(e.g. the carotid); 3) history
             of bleeding related to tumor or radiotherapy during or after the completion of
             radiation.

          -  Evidence of active central nervous system hemorrhage.

          -  History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess
             within 28 days prior to study enrollment.

          -  inadequately controlled hypertension (systolic blood pressure (SBP) > 140 mmHg and/or
             diastolic blood pressure (DBP) > 90 mmHg despite antihypertensive medication)

          -  Severe complications: 1) History of large vessel cerebrovascular accident (CVA) within
             6 months; 2) Myocardial infarction or unstable angina within 6 months; 3) New York
             heart association grade II or greater congestive heart failure; 4) Serious and
             inadequately controlled cardiac arrhythmia; 5) Significant vascular disease (e.g.
             aortic aneurysm, history of aortic dissection); 6) Clinically significant peripheral
             vascular disease; 7) severe infection.

          -  Evidence of bleeding diathesis or coagulopathy.

          -  Patients who have received steroid therapy for radiation-induced brain necrosis before
             the study.

          -  History of anaphylactic response to bevacizumab.