Gliadel therapy given for first resection of malignant glioma: a single centre study of the potential use of Gliadel

Abstract

The results of a recently concluded phase III study have shown that Gliadel therapy (biodegradable polymer impregnated with 3.85% BCNU placed into the surgical cavity) significantly prolongs survival and time to relapse in patients having initial resective surgery for malignant glioma followed by radiotherapy. The indications and exclusion criteria for patients in this study were well defined. To determine the relative frequencies of Gliadel 'eligible' and 'ineligible' patients, and differences in prognostic variables between these two cohorts, we conducted a review of all Edinburgh patients with an initial diagnosis of malignant glioma managed throughout the period of patient accrual into the phase III Gliadel study (Edinburgh was one of 38 contributing centres). Independent predictors of outcome were taken from the MRC prognostic index. Analysis was done on an intention to treat basis. Only 25% of patients (14/56) with malignant glioma managed over this period were eligible for the Gliadel study and all were recruited. The patients in the study group were younger (median 51 v. 59 years, p = 0.085); in better clinical grade (median Karnofsky score 85 v. 80, p = 0.038); more likely to have resective surgery (86% v. 38%, p = 0.0001); more likely to have postoperative radiotherapy (93% v. 55%, p = 0.0001) and more likely to survive longer, even though one half of the Gliadel cohort received placebo, (66 v. 19 weeks, p = 0.06) than those not eligible. If the future use of Gliadel is limited to the eligibility criteria used in the phase III trial about 20% (95% confidence intervals 13-34%) of patients with newly diagnosed malignant glioma will receive this therapy.

Independent association of extent of resection with survival in patients with malignant brain astrocytoma

“…Given the reported survival benefit ob-served with Gliadel wafer implantation (2.87% 1,3-bis-(2chloroethyl)-1-nitrosourea; MGI Pharma) 21,39,40 and postoperative temozolomide therapy, 35 we recorded whether patients received Gliadel wafer implantation or adjuvant postoperative temozolomide therapy at any point after surgery in addition to radiotherapy. It was also recorded whether patients underwent a subsequent resection for tumor progression at a later date.…”

The effectiveness and cost-effectiveness of carmustine implants and temozolomide for the treatment of newly diagnosed high-grade glioma: a systematic review and economic evaluation

“…Based on participation in Westphal and colleagues' RCT, 151 Whittle and colleagues estimated that 25% (95% CI 16 to 38%) of patients presenting to their Edinburgh unit with high-grade glioma would be eligible for BCNU-W implantation, with about 21% (95% CI 13 to 34%) actually receiving it. 146 Although increasing the upper age limit could enhance generalisibility, BCNU-W use in practice is also limited to larger, accessible tumours.…”

“…Whittle and colleagues estimate that 25% [95% confidence interval (CI) 16 to 38] of patients presenting to their Edinburgh unit with high-grade glioma would be eligible for BCNU-W implantation, and that about 21% (95% CI 13 to 34) would receive it. 146 Using the CIs, this represents about 1-3 people per year in an average District General Hospital, at a cost of £6105-18,315 over 5 years. In England, this represents about £1.4-3.6 million over 5 years, three-quarters of the cost coming in the first year.…”

NICE guidance on the use of carmustine wafers in high grade gliomas: a national study on variation in practice

“…Even if we appreciate that only a quarter of glioblastoma patients might be eligible for carmustine wafers and would fit within the inclusion criteria of this study,18 the small number of patients recruited from some centres would suggest there has been selection bias in these centres. If we were to assume an incidence of 4 per 100 000 for high grade gliomas,19 we would expect 1280 patients diagnosed per year in the study population.…”