title: Chemotherapeutic wafers for High Grade Glioma.
abstract: BACKGROUND
  Standard treatment for high grade glioma (HGG) usually entails biopsy or surgical resection where possible followed by radiotherapy. Systemic chemotherapy is usually only given in selected cases and its use is often limited by side effects. Implanting wafers impregnated with chemotherapy agents into the resection cavity represents a novel means of delivering drugs to the central nervous system (CNS) with fewer side effects. It is not clear how effective this modality is or whether it should be recommended as part of standard care for HGG.
  
  
  OBJECTIVE
  To assess whether chemotherapeutic wafers have any advantage over conventional therapy for HGG.
  
  
  METHODS
  The following databases were searched: The Cochrane Central Register of Controlled Trials (CENTRAL), Issue 2, 2007, MEDLINE, EMBASE, SCIENCE CITATION INDEX, Physician Data Query and the meta-Register of Controlled Trials. Reference lists of all identified studies were searched. The Journal of Neuro-Oncology was hand searched from 1999 to 2007, including all conference abstracts. Neuro-oncologists were contacted regarding ongoing and unpublished trials.
  
  
  METHODS
  Patients included those of all ages with a presumed diagnosis of malignant glioma from clinical examination and radiology. Interventions included insertion of chemotherapeutic wafers to the resection cavity at either primary surgery or for recurrent disease. Included studies had to be randomised controlled trials (RCTs).
  
  
  METHODS
  Quality assessment and data extraction were undertaken by two review authors. Outcome measures included survival, time to progression, quality of life (QOL) and adverse events.
  
  
  RESULTS
  In primary disease two RCTs assessing the effect of carmustine impregnated wafers (Gliadel(R)) and enrolling a total of 272 participants were identified. Survival was increased (hazard ratio (HR) 0.65 confidence interval (CI) 0.48 to 0.86 p = 0.003). In recurrent disease a single RCT was included assessing the effect of Gliadel(R) and enrolling 222 participants. It did not demonstrate a significant survival increase (HR 0.83 CI 0.62 to 1.10 p = 0.2). There was no suitable data for time to progression or QOL. Adverse events were not more common in either arm, and were presented in a descriptive fashion.
  
  
  CONCLUSIONS
  Gliadel(R) results in a prolongation of survival without an increased incidence of adverse events when used as primary therapy. There is no evidence of enhanced progression free survival (PFS) or QOL. In recurrent disease, Gliadel(R) does not appear to confer any added benefit. These findings are based on the results of three RCTs with approximately 500 patients in total.
authors.affiliation: Clinical Neurosciences, Bramwell Dott Building, Western General Hospital, Crewe Road, Edinburgh, Midlothian, UK, EH4 2XU. m.g.hart@doctors.net.uk
authors.forename: Michael G
authors.initials: MG
authors.lastname: Hart
authors.forename: Robert
authors.initials: R
authors.lastname: Grant
authors.forename: Ruth
authors.initials: R
authors.lastname: Garside
authors.forename: Gabriel
authors.initials: G
authors.lastname: Rogers
authors.forename: Margaret
authors.initials: M
authors.lastname: Somerville
authors.forename: Ken
authors.initials: K
authors.lastname: Stein
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000601:surgery; D002330:Carmustine / Q000008:administration & dosage*; D003131:Combined Modality Therapy / Q000379:methods; D005910:Glioma / Q000188:drug therapy* / Q000601:surgery; D006801:Humans; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D016032:Randomized Controlled Trials as Topic
chemical_list: D018906:Antineoplastic Agents, Alkylating; D002330:Carmustine