Last Updated:9/12/2013 - This page reviewed and approved by Virginia Stark-Vance, M.D.
Pivotal study: A double-blind, randomized, placebo-controlled study of Gliadel wafers as an adjunct to surgery and radiation in 240 patients with newly diagnosed high-grade glioma
Initial publication of study results
Westphal M, Hilt DC, Bortey E, Delavault P, et al. A phase 3 trial of local chemotherapy with biodegradable carmustine (BCNU) wafers (Gliadel wafers) in patients with primary malignant glioma. Neuro Oncol. 2003;5(2):79-88.
A previous placebo-controlled trial has shown that biodegradable 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) wafers (Gliadel wafers) prolong survival in patients with recurrent glioblastoma multiforme. A previously completed phase 3 trial, also placebo controlled, in 32 patients with newly diagnosed malignant glioma also demonstrated a survival benefit in those patients treated with BCNU wafers. Because of the small number of patients in that trial, a larger phase 3 trial was performed to confirm these results.
Two hundred forty patients were randomized to receive either BCNU or placebo wafers at the time of primary surgical resection; both groups were treated with external beam radiation postoperatively. The two groups were similar for age, sex, Karnofsky performance status (KPS), and tumor histology.
Median survival in the intent-to-treat group was 13.9 months for the BCNU wafer-treated group and 11.6 months for the placebo-treated group (log-rank p-value stratified by country = 0.03), with a 29% reduction in the risk of death in the treatment group. When adjusted for factors affecting survival, the treatment effect remained positive with a risk reduction of 28% (p = 0.03). Time to decline in KPS and in 10/11 neuroperformance measures was statistically significantly prolonged in the BCNU wafer-treated group p â‰¤0.05). Adverse events were comparable for the 2 groups, except for CSF leak (5% in the BCNU wafer-treated group vs. 0.8% in the placebo-treated group) and intracranial hypertension (9.1% in the BCNU wafer-treated group vs. 1.7% in the placebo group).
This study confirms that local chemotherapy with BCNU wafers is well tolerated and offers a survival benefit to patients with newly diagnosed malignant glioma.
Publication of long-term study results: Gliadel wafer in initial surgery for malignant glioma: long-term follow-up of a multicenter controlled trial.
Westphal M, Ram Z, Riddle V, Hilt D, et al; Executive Committee of the Gliadel Study Group. Gliadel wafer in initial surgery for malignant glioma: long-term follow-up of a multicenter controlled trial. Acta Neurochir (Wien). 2006;148(3):269-275; discussion 275.
Objective: Adjuvant systemic chemotherapy increases survival of primary malignant glioma patients beyond 12-18 months. The only interstitial chemotherapy treatment approved for malignant glioma is Gliadel wafer containing carmustine (BCNU) placed in the resection cavity at surgery. Analysis of a large trial by Westphal and colleagues (n = 240) showed a 29% risk reduction (p = 0.03) in the BCNU wafer-treated group over the course of the 30-month trial. Long-term follow-up of these patients was undertaken to determine the survival benefit at 2 and 3 years.
Methods: Survival proportions for the placebo and treatment groups over the 56-month study were estimated by the Kaplan-Meier method. Multiple-regression analyses using the Cox proportional hazards model included prognostic factors of age, KPS, and tumor type. A secondary analysis was conducted for 207 GBM patients.
Results: Of the 59 patients available for long-term follow-up, 11 were alive at 56 months: 9 had received BCNU wafers and 2 had received placebo wafers. Median survival of patients treated with BCNU wafers was 13.8 months vs 11.6 months in placebo-treated patients (p = 0.017) with a hazard ratio of 0.73 (p = 0.018), representing a 27% significant risk reduction. This survival advantage was maintained at 1, 2, and 3 years and was statistically significant (p = 0.01) at 3 years. Two of 207 GBM patients remained alive at the end of the follow-up period, both in the BCNU wafer-treated group.
Conclusion: Malignant glioma patients treated with BCNU wafers at the time of initial surgery in combination with radiation therapy demonstrated a survival advantage at 2 and 3 years follow-up compared
Overall Survival of Newly Diagnosed
Glioblastoma Patients Receiving
Carmustine Wafers Followed by Radiation
and Concurrent Temozolomide Plus
Rotational Multiagent Chemotherapy
- Published online:June 9, 2009VC 2009 American Cancer Society
BACKGROUND:Glioblastoma multiforme (GBM), the most lethal type of brain tumor, has a 1-year median
survival. The effect of carmustine wafers on the survival of newly diagnosed GBM patients treated with
radiotherapy (RT) and concurrent temozolomide (TMZ) plus RT plus rotational chemotherapy was investi-gated.
METHODS:An institutional review board-approved retrospective study was conducted in 85 newly
diagnosed GBM patients who received surgical resection with and without carmustine wafers followed by
RT and concurrent TMZ plus rotational chemotherapy. Treatment group comparisons were conducted using
the log-rank test. Survival experience of the Duke cohort was examined within specific patient subgroups
defined by the original Radiation Therapy Oncology Group (RTOG) recursive partition analysis (RPA) class
and compared with the European Organization for Research and Treatment of Cancer (Stupp) and RTOG
RESULTS: Overall 1- and 2-year survival for the noncarmustine wafer cohort were 69% and 29%,
respectively, with a median survival of 72.7 weeks. One- and 2-year survival for the carmustine wafer cohort
were 81% and 47%, with median survival of 89.5 weeks. Carmustine wafer was not an independent predictor
(PÂ¼.110) of survival after adjustment for RPA class. The proportion of patients in the carmustine wafer
cohort who lived longer than predicted based upon Stupp regimen results was significantly greater than
0.5 (P<.006); similar results based upon the RTOG trial data were observed (P<.001).
Carmustine wafer with concurrent TMZ and radiation followed by rotational chemotherapy is a well toler-ated, effective therapy, and has a survival benefit compared with radiation alone. Prospective randomized
trials are needed to rigorously compare the carmustine wafer regimen to the Stupp and postradiation
multimodality regimens.Cancer 2009;115:3501â€“11.VC 2009 American Cancer Society.
KEY WORDS:glioma, surgery, BCNU wafer, radiotherapy, temozolomide
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