Question: What is the safety and efficacy of interstitial chemotherapy with carmustine-loaded polymers (Gliadel wafers: MGI Pharma, Bloomington, MN, U.S.A.) in the treatment of newly diagnosed or recurrent malignant glioma (that is, glioblastoma multiforme, anaplastic astrocytoma, anaplastic oligoastrocytoma, and anaplastic oligodendroglioma)?
Perspectives: Malignant glioma is the most common type of primary brain tumour in adults. In general, efficacy of systemic therapy in this patient population has been disappointing, and novel treatment approaches are needed. Because several randomized controlled trials (RCTS) investigating the safety and efficacy of Gliadel are available, the Neuro-oncology Disease Site Group of Cancer Care Ontario's Program in Evidence-Based Care decided that a systematic review of the evidence was necessary.
Outcomes: The outcomes of interest for this review were overall survival, adverse events, and quality of life.
Methodology: Systematic searches of the medline, embase, and Cochrane Library databases were conducted for relevant evidence. Fully-published reports of RCTS comparing treatment with Gliadel wafers to placebo or alternative treatment were selected for inclusion. Prospective cohort studies were also included.
Results: Two RCTS that compared Gliadel to placebo in patients with newly diagnosed malignant glioma were obtained. Both RCTS reported a significant survival benefit for patients who received Gliadel as compared with patients in the control group. One RCT and one prospective cohort study were obtained that examined the role of Gliadel in patients with recurrent malignant glioma. The rct demonstrated a significant survival benefit for Gliadel only after adjustment for prognostic factors, and the prospective cohort study reported no survival benefit for Gliadel as compared with a historical control group. All three RCTS reported similar rates of adverse events in the treatment and control groups. The most frequently reported adverse events were convulsions, confusion, brain edema, infection, hemiparesis, aphasia, and visual field defects.
Conclusions: Gliadel is an option for selected patients with newly diagnosed malignant glioma where a near gross total resection is possible. No evidence is available comparing Gliadel with systemic therapy, and a decision to combine Gliadel with systemic therapy should be made for patients individually. The patient population that would benefit from Gliadel (age, histology, and performance status) is unclear; further investigation is needed. Gliadel is also an option for patients with surgically resectable recurrent malignant glioma.
Keywords: Gliadel; carmustine; glioblastoma; interstitial chemotherapy; malignant glioma; systematic review.