Treatment of high grade glioma with anti-cancer drug (chemotherapy) coated implants

High grade glioma is a rapidly progressive form of brain tumour. Standard therapy involves the use of surgery (either biopsy or resection) and radiotherapy plus or minus temozolomide. Chemotherapy was not previously used due to concerns over efficacy and high risks of side effects.

We found two trials, enrolling 272 people in total, with newly diagnosed high grade glioma, that studied the effects of implanting wafers coated with an anti-cancer drug called carmustine (Gliadel®) in the area where the tumour was removed. This was compared with implanting wafers that contained no drug. Both groups received radiotherapy afterwards. Patients who received carmustine wafers had a longer survival without a demonstrably higher incidence of adverse events (side effects).

A similar trial enrolled 222 people who had already been diagnosed with a high grade glioma and received surgery but had then had a relapse of disease. In this situation the trial found that Gliadel® did not improve survival or any other outcome measure looked at.

Authors' conclusions: 

Carmustine impregnated wafers (Gliadel®) result in improved survival without an increased incidence of adverse events over placebo wafers when used for primary disease therapy. There is no evidence of benefit for any other outcome measures. In recurrent disease Gliadel® does not appear to confer any additional benefit.

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Background: 

Standard treatment for high grade glioma (HGG) usually entails surgery (either biopsy or resection) followed by radiotherapy plus or minus temozolomide. Implanting wafers impregnated with chemotherapy agents into the resection cavity represents a novel means of delivering drugs directly to the resection cavity with potentially fewer systemic side effects. It is not clear how effective this modality is or whether it should be recommended as part of standard care for patients with HGG.

Objectives: 

To estimate the clinical effectiveness of chemotherapy wafers for patients with HGG.

Search strategy: 

The following databases were searched: CENTRAL (issue 4. 2010); MEDLINE and EMBASE. The original search strategy also included: 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 and Neuro-oncology were hand searched from 1999 to 2010, including all conference abstracts. Neuro-oncologists, trial authors and drug manufacturers were contacted regarding ongoing and unpublished trials.

Selection criteria: 

Patients included those of all ages with a histologically proven diagnosis of HGG (using intra-operative analysis when undergoing first resection). Therapy could be instigated for either newly diagnosed disease (primary therapy) or at recurrence. Interventions included insertion of chemotherapy wafers to the resection cavity. Included studies had to be randomised controlled trials (RCTs).

Data collection and analysis: 

Two independent review authors assessed the search results for relevance and undertook critical appraisal according to pre-specified guidelines.

Main results: 

In primary disease two RCTs assessing the effect of carmustine impregnated wafers (Gliadel®) and enrolling a total of 272 participants were identified. Survival was increased with Gliadel® compared to placebo (hazard ratio (HR) 0.65, 95% Confidence Interval (CI) 0.48 to 0.86, P = 0.003). In recurrent disease a single RCT was included comparing Gliadel® with placebo and enrolled 222 participants. It did not demonstrate a significant survival increase (HR 0.83, 95% CI 0.62 to 1.10, P = 0.2). There was no suitable data for any of the secondary outcome measures. Adverse events were not more common in either arm and are presented in a descriptive fashion.

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