Newly Diagnosed Malignant Glioma
Two randomized controlled trials (RCTs) compared the efficacy of Gliadel® versus placebo in patients with newly diagnosed gliomas. In the largest RCT to date, a two-month improvement in median survival for patients with newly diagnosed malignant glioma receiving Gliadel® compared to patients who received a placebo was reported (p=0.017). In addition, the analysis of the survival curves revealed a significant 27% reduction in risk of mortality for patients who received Gliadel® (p=0.018). A survival advantage of Gliadel® for patients with glioblastoma multiforme (GBM) was not detected, although the trial was not designed to make comparisons between histological subgroups. Another randomized trial only included 32 patients newly diagnosed with malignant glioma, because the researchers were unable to obtain Gliadel® during the trial. While a survival benefit was reported for Gliadel® in the entire patient population and for patients with GBM, no conclusions could be reached based on this small number of patients.
Both studies reported similar adverse effects in the treatment and control arms. The most common adverse effects associated with Gliadel® were hemiplegia, convulsions, confusion, and brain edema. The most commonly reported adverse effects among patients receiving the placebo were convulsions, confusion, brain edema, and aphasia. A significantly higher number of patients experienced intracranial hypertension in the Gliadel® arm of the Westphal trial. Since neither trial included a comparison with systemic therapy, it is unclear how the adverse effect rates associated with interstitial chemotherapy wafers compares to the rates expected with systemic chemotherapy.
As the largest trial does demonstrate a survival advantage in the Gliadel® treatment arm, Gliadel® may be considered an option in the subgroup of patients with newly diagnosed resectable malignant gliomas. However, the patient population (based on age, histology, performance status, etc.) that would benefit from Gliadel® is unclear and needs to be further investigated. In addition, no comparison has been performed between the efficacy of interstitial and systemic chemotherapy; therefore, clinicians should review the latest evidence for the benefit of systemic chemotherapy in patients with newly diagnosed malignant glioma. (See Practice Guideline #9-2 Adjuvant Systemic Chemotherapy, Following Surgery and External Beam Radiotherapy, for Adults with Newly Diagnosed Malignant Glioma).
Recurrent Malignant Glioma
One RCT compared the efficacy of Gliadel® versus placebo in patients with recurrent gliomas. The overall result of that trial was negative, with no significant survival advantage seen in the primary analysis; however, a survival advantage for Gliadel® in the entire patient population and in patients with GBM was observed after the adjustment for prognostic factors. As there were no a priori subgroups identified, the results of the subgroup analysis of GBM patients should be interpreted with caution. While no survival advantage for Gliadel® was detected in the cohort study with historical control, no conclusions can be reached due to the heterogeneity between patients and potential for bias in such studies. The positive results of the RCT after the adjustment for prognostic factors suggest that Gliadel® may increase overall survival in some patients with recurrent resectable malignant glioma. Since those patients generally have a poor outlook, any treatment that has the potential for prolonging life without significant adverse effects should be considered as an option.
