Gliadel® wafer in initial surgery for malignant glioma: long-term follow-up of a multicenter controlled trial
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 with placebo.
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- Brem, H, Piantadosi, S, Burger, PC, Walker, M, Selker, R, Vick, NA, Black, K, Sisti, M, Brem, S, Mohr, G 1995Placebo-controlled trial of safety and efficacy of intraoperative controlled delivery by biodegradable polymers of chemotherapy for recurrent gliomas. The Polymer-brain Tumor Treatment Group.Lancet34510081012CrossRefPubMedGoogle Scholar
- CBTRUS (2004) Statistical Report: Primary Brain Tumors in the United States, 1997–2001. Published by the Central Brain Tumor Registry of the United StatesGoogle Scholar
- Gutin, PH, Prados, MD, Phillips, TL, Wara, WM, Larson, DA, Leibel, SA, Sneed, PK, Levin, VA, Weaver, KA, Silver, P 1991External irradiation followed by an interstitial high activity iodine-125 implant “boost” in the initial treatment of malignant gliomas: NCOG study 6G-82-2.Int J Radiat Oncol Biol Phys21601606PubMedGoogle Scholar
- Leibel, SA, Gutin, PH, Wara, WM, Silver, PS, Larson, DA, Edwards, MS, Lamb, SA, Ham, B, Weaver, KA, Barnett, C 1989Survival and quality of life after interstitial implantation of removable high-activity iodine-125 sources for the treatment of patients with recurrent malignant gliomas.Int J Radiat Oncol Biol Phys1711291139PubMedGoogle Scholar
- Meldorf MG, Riddle VD, Gliadel Multicenter Trial Group, Agarwal S (2003) Long-term efficacy of local chemotherapy with biodegradable carmustine implants (Gliadel) in high-grade malignant gliomas. Paper presented at: American Association of Neurological Surgeons (AASN) 2003 Annual Meeting Scientific Program; April 26, 2003; San Diego, CAGoogle Scholar
- Westphal, M, Hilt, DC, Bortey, E, Delavault, P, Olivares, R, Warnke, PC, Whittle, IR, Jaaskelainen, J, Ram, Z 2003A phase III trial of local chemotherapy with biodegradable carmustine (BCNU) wafers (Gliadel wafers) in patients with primary malignant glioma.Neuro-oncol57988CrossRefPubMedGoogle Scholar