title: Phase II trial of thalidomide and carmustine for patients with recurrent high-grade gliomas.
abstract: OBJECTIVE
  The use of thalidomide as an antiangiogenic agent has met with only limited success in the treatment of malignant gliomas. On the basis of preclinical data demonstrating synergistic antitumor activity when antiangiogenic agents are combined with cytotoxic agents, we explored the clinical activity of the combination of thalidomide and carmustine (BCNU) in patients with recurrent high-grade gliomas.
  
  
  METHODS
  Patients with a histologic diagnosis of high-grade glioma and radiographic evidence of tumor progression after standard surgery, radiation, and chemotherapy were eligible for the study. Patients received BCNU 200 mg/m2 on day 1 of every 6-week cycle, and 800 mg/d of thalidomide that was escalated to a maximal dose of 1,200 mg/d as tolerated.
  
  
  RESULTS
  A total of 40 patients (38 with glioblastomas, two with anaplastic gliomas) were accrued to the study. The combination of thalidomide and BCNU was well tolerated; mild myelosuppression and mild to moderate sedation were the most common side effects. The median progression-free survival (100 days) and the objective radiographic response rate (24%) for patients with glioblastoma compared favorably with data from historical controls.
  
  
  CONCLUSIONS
  This is one of the first clinical trials to evaluate the strategy of combining a putative antiangiogenic agent with a cytotoxic agent in patients with primary brain tumors. Our data demonstrate that thalidomide in combination with BCNU is well tolerated and has antitumor activity in patients with recurrent high-grade gliomas. Although the combination seems to be more active than either agent alone, such conclusions await confirmatory trials.
authors.affiliation: Neuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Drive, MSC 1911, Building 10, Room 12S245, Bethesda, MD 20892-1911, USA. hfine@mail.nih.gov
authors.forename: Howard A
authors.initials: HA
authors.lastname: Fine
authors.forename: Patrick Y
authors.initials: PY
authors.lastname: Wen
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Maher
authors.forename: Elene
authors.initials: E
authors.lastname: Viscosi
authors.forename: Tracy
authors.initials: T
authors.lastname: Batchelor
authors.forename: Nehal
authors.initials: N
authors.lastname: Lakhani
authors.forename: William D
authors.initials: WD
authors.lastname: Figg
authors.forename: Benjamin W
authors.initials: BW
authors.lastname: Purow
authors.forename: Craig B
authors.initials: CB
authors.lastname: Borkowf
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000628:therapy; D002330:Carmustine / Q000008:administration & dosage; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D018450:Disease Progression; D005260:Female; D005910:Glioma / Q000188:drug therapy* / Q000628:therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D013792:Thalidomide / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D013792:Thalidomide; D002330:Carmustine