Annals of Surgical Oncology

, 15:2887 | Cite as

Use of Gliadel (BCNU) Wafer in the Surgical Treatment of Malignant Glioma: A 10-Year Institutional Experience

  • Frank J. Attenello
  • Debraj Mukherjee
  • Ghazala Datoo
  • Matthew J. McGirtEmail author
  • Eileen Bohan
  • Jon D. Weingart
  • Alessandro Olivi
  • Alfredo Quinones-Hinojosa
  • Henry Brem



Gliadel (polifeprosan 20 with carmustine [BCNU] implant) is commonly used for local delivery of BCNU to high-grade gliomas after resection and is associated with increased survival. Various complications of Gliadel wafers have been reported but not consistently reproduced. We set out to characterize Gliadel-associated morbidity in our 10-year experience with Gliadel wafers for treatment of malignant glioma.


We retrospectively reviewed records of 1013 patients undergoing craniotomy for resection of malignant brain astrocytoma (World Health Organization grade III/IV disease). Perioperative morbidity occurring within 3 months of surgery was assessed for patients and compared between patients receiving versus not receiving Gliadel wafer. Overall survival was assessed for all patients.


A total of 1013 craniotomies were performed for malignant brain astrocytoma. A total of 288 (28%) received Gliadel wafer (250 glioblastoma multiforme (GBM), 38 anaplastic astrocytoma/anaplastic oligodendroglioma (AA/AO), 166 primary resection, 122 revision resection). Compared with the non-Gliadel cohort, patients receiving Gliadel were older (55 ± 14 vs. 50 ± 17, P = .001) and more frequently underwent gross total resection (75% vs 36%, P < .01) but otherwise similar. Patients in Gliadel versus non-Gliadel cohorts had similar incidences of perioperative surgical site infection (2.8% vs. 1.8%, P = .33), cerebrospinal fluid leak (2.8% vs. 1.8%, P = .33), meninigitis (.3% vs. .3%, P = 1.00), incisional wound healing difficulty (.7% vs. .4%, P = .63), symptomatic malignant edema (2.1% vs. 2.3%, P = 1.00), 3-month seizure incidence (14.6% vs. 15.7%, P = .65), deep-vein thrombosis (6.3% vs. 5.2%, P = .53), and pulmonary embolism (PE) (4.9% vs. 3.7%, P = .41). For patients receiving Gliadel for GBM, median survival was 13.5 months after primary resection (20% alive at 2 years) and 11.3 months after revision resection (13% alive at 2 years). For patients receiving Gliadel for AA/AO, median survival was 57 months after primary resection (66% alive at 2 years) and 23.6 months after revision resection (47% alive at 2 years).


In our experience, use of Gliadel wafer was not associated with an increase in perioperative morbidity after surgical treatment of malignant astrocytoma.


Gliadel Polymer delivery Complications Malignant astrocytoma 


  1. 1.
    Fisher PG, Buffler PA. Malignant gliomas in 2005: where to go from here? JAMA 2005; 293:615–7.PubMedCrossRefGoogle Scholar
  2. 2.
    Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2007. CA Cancer J Clin 2007; 57:43–66.PubMedGoogle Scholar
  3. 3.
    Reardon DA, Rich JN, Friedman HS, et al. Recent advances in the treatment of malignant astrocytoma. J Clin Oncol 2006; 24:1253–65.PubMedCrossRefGoogle Scholar
  4. 4.
    Kornblith PL, Walker M. Chemotherapy for malignant gliomas. J Neurosurg 1988; 68:1–17.PubMedGoogle Scholar
  5. 5.
    Ohgaki H, Kleihues P. Genetic pathways to primary and secondary glioblastoma. Am J Pathol 2007; 170:1445–53.PubMedCrossRefGoogle Scholar
  6. 6.
    Fine HA, Dear KB, Loeffler JS, et al. Meta-analysis of radiation therapy with and without adjuvant chemotherapy for malignant gliomas in adults. Cancer 1993; 71:2585–97.PubMedCrossRefGoogle Scholar
  7. 7.
    Stupp R, Mason WP, Van den Bent MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 2005; 352:987–96.PubMedCrossRefGoogle Scholar
  8. 8.
    Stewart LA. Chemotherapy in adult high-grade glioma: a systematic review and meta-analysis of individual patient data from 12 randomised trials. Lancet 2002; 359:1011–8.PubMedCrossRefGoogle Scholar
  9. 9.
    Mutter N, Stupp R. Temozolomide: a milestone in neuro-oncology and beyond? Expert Rev Anticancer Ther 2006; 6:1187–204.PubMedCrossRefGoogle Scholar
  10. 10.
    Patchell RA, Regine WF, Loeffler JS, et al. Radiosurgery plus whole-brain radiation therapy for brain metastases. JAMA 2006; 296:2089–90.PubMedCrossRefGoogle Scholar
  11. 11.
    Ewend MG, Brem S, Gilbert M, et al. Treatment of single brain metastasis with resection, intracavity carmustine polymer wafers, and radiation therapy is safe and provides excellent local control. Clin Cancer Res 2007; 13:3637–41.PubMedCrossRefGoogle Scholar
  12. 12.
    Gururangan S, Cokgor L, Rich JN, et al. Phase I study of Gliadel wafers plus temozolomide in adults with recurrent supratentorial high-grade gliomas. Neuro Oncol 2001; 3:246–50.PubMedGoogle Scholar
  13. 13.
    Heery CR, Desjardins A, Quinn JA. Acute toxicity analysis of patients receiving surgery, Gliadel wafer implantation, and postoperative daily temozolomide with radiation therapy for primary high-grade glioma. Proc Am Soc Clin Oncol 2006; 24:11504.Google Scholar
  14. 14.
    La Rocca RV, Hodes J, Villanueva WG. A phase II study of radiation with concomitant and then sequential temozolomide (TMZ) in patients with newly diagnosed supratentorial high-grade malignant glioma who have undergone surgery with carmustine (BCNU) wafer insertion. Neuro Oncol 2006; 8:391–500.CrossRefGoogle Scholar
  15. 15.
    Gaspar LE, Fisher BJ, Macdonald DR, et al. Supratentorial malignant glioma: patterns of recurrence and implications for external beam local treatment. Int J Radiat Oncol Biol Phys 1992; 24:55–7.PubMedGoogle Scholar
  16. 16.
    Guerin C, Laterra J, Hruban RH, et al. The glucose transporter and blood-brain barrier of human brain tumors. Ann Neurol 1990; 28:758–65.PubMedCrossRefGoogle Scholar
  17. 17.
    Walker MD, Alexander E Jr, Hunt WE, et al. Evaluation of BCNU and/or radiotherapy in the treatment of anaplastic gliomas. A cooperative clinical trial. J Neurosurg 1978; 49:333–43.PubMedGoogle Scholar
  18. 18.
    Sandberg-Wollheim M, Malmstrom P, Stromblad LG, et al. A randomized study of chemotherapy with procarbazine, vincristine, and lomustine with and without radiation therapy for astrocytoma grades 3 and/or 4. Cancer 1991; 68:22–9.PubMedCrossRefGoogle Scholar
  19. 19.
    Fung LK, Ewend MG, Sills A, et al. Pharmacokinetics of interstitial delivery of carmustine, 4-hydroperoxycyclophosphamide, and paclitaxel from a biodegradable polymer implant in the monkey brain. Cancer Res 1998; 58:672–84.PubMedGoogle Scholar
  20. 20.
    Tamargo RJ, Epstein JI, Reinhard CS, et al. Brain biocompatibility of a biodegradable, controlled-release polymer in rats. J Biomed Mater Res 1989; 23:253–66.PubMedCrossRefGoogle Scholar
  21. 21.
    Brem H, Tamargo RJ, Olivi A, et al. Biodegradable polymers for controlled delivery of chemotherapy with and without radiation therapy in the monkey brain. J Neurosurg 1994; 80:283–90.PubMedCrossRefGoogle Scholar
  22. 22.
    Ewend MG, Williams JA, Tabassi K, et al. Local delivery of chemotherapy and concurrent external beam radiotherapy prolongs survival in metastatic brain tumor models. Cancer Res 1996; 56:5217–23.PubMedGoogle Scholar
  23. 23.
    Ewend MG, Sampath P, Williams JA, et al. Local delivery of chemotherapy prolongs survival in experimental brain metastases from breast carcinoma. Neurosurgery 1998; 43:1185–93.PubMedCrossRefGoogle Scholar
  24. 24.
    Withrow SJ, Liptak JM, Straw RC, et al. Biodegradable cisplatin polymer in limb-sparing surgery for canine osteosarcoma. Ann Surg Oncol 2004; 11:705–13.PubMedCrossRefGoogle Scholar
  25. 25.
    Brem H, Langer R. Polymer-based drug delivery to the brain. Sci Med 1996; 3:2–11.Google Scholar
  26. 26.
    Brem H, Mahaley MS Jr, Vick NA, et al. Interstitial chemotherapy with drug polymer implants for the treatment of recurrent gliomas. J Neurosurg 1991; 74:441–6.PubMedGoogle Scholar
  27. 27.
    Brem H, Piantadosi S, Burger PC, et al. Placebo-controlled trial of safety and efficacy of intraoperative controlled delivery by biodegradable polymers of chemotherapy for recurrent gliomas. The Polymer-brain Tumor Treatment Group. Lancet 1995; 345:1008–12.PubMedCrossRefGoogle Scholar
  28. 28.
    Sipos EP, Tyler B, Piantadosi S, et al. Optimizing interstitial delivery of BCNU from controlled release polymers for the treatment of brain tumors. Cancer Chemother Pharmacol 1997; 39:383–9.PubMedCrossRefGoogle Scholar
  29. 29.
    Olivi A, Grossman SA, Tatter S, et al. Dose escalation of carmustine in surgically implanted polymers in patients with recurrent malignant glioma: a New Approaches to Brain Tumor Therapy CNS Consortium trial. J Clin Oncol 2003; 21:1845–9.PubMedCrossRefGoogle Scholar
  30. 30.
    Valtonen S, Timonen U, Toivanen P, et al. Interstitial chemotherapy with carmustine-loaded polymers for high-grade gliomas: a randomized double-blind study. Neurosurgery 1997; 41:44–8.PubMedCrossRefGoogle Scholar
  31. 31.
    Westphal M, Hilt DC, Bortey E, 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; 5:79–88.PubMedCrossRefGoogle Scholar
  32. 32.
    Whittle IR, Lyles S, Walker M. Gliadel therapy given for first resection of malignant glioma: a single centre study of the potential use of Gliadel. Br J Neurosurg 2003; 17:352–4.PubMedCrossRefGoogle Scholar
  33. 33.
    Lawson HC, Sampath P, Bohan E, et al. Interstitial chemotherapy for malignant gliomas: the Johns Hopkins experience. J Neurooncol 2007; 83:61–70.PubMedCrossRefGoogle Scholar
  34. 34.
    Limentani SA, Asher A, Heafner M, et al. A phase I trial of surgery, Gliadel wafer implantation, and immediate postoperative carboplatin in combination with radiation therapy for primary anaplastic astrocytoma or glioblastoma multiforme. J Neurooncol 2005; 72:241–4.PubMedCrossRefGoogle Scholar
  35. 35.
    Kleinberg LR, Weingart J, Burger P, et al. Clinical course and pathologic findings after Gliadel and radiotherapy for newly diagnosed malignant glioma: implications for patient management. Cancer Invest 2004; 22:1–9.PubMedCrossRefGoogle Scholar
  36. 36.
    Brem H, Ewend MG, Piantadosi S, et al. The safety of interstitial chemotherapy with BCNU-loaded polymer followed by radiation therapy in the treatment of newly diagnosed malignant gliomas: phase I trial. J Neurooncol 1995; 26:111–23.PubMedCrossRefGoogle Scholar
  37. 37.
    Westphal M, Ram Z, Riddle V, et al. Gliadel wafer in initial surgery for malignant glioma: long-term follow-up of a multicenter controlled trial. Acta Neurochir (Wien) 2006; 148:269–75.CrossRefGoogle Scholar
  38. 38.
    Bohan E, Brem H. Treatment of brain tumors by local delivery of chemotherapy via biodegradable polymers. Hosp Pharm Rep 1997; 12–6Google Scholar
  39. 39.
    Engelhard HH. Tumor bed cyst formation after BCNU wafer implantation: report of two cases. Surg Neurol 2000; 53:220–4.PubMedCrossRefGoogle Scholar
  40. 40.
    McGirt MJ, Villavicencio AT, Bulsara KR, et al. Management of tumor bed cysts after chemotherapeutic wafer implantation. Report of four cases. J Neurosurg 2002; 96:941–5.PubMedGoogle Scholar
  41. 41.
    Weber EL, Goebel EA. Cerebral edema associated with Gliadel wafers: two case studies. Neuro Oncol 2005; 7:84–9.PubMedCrossRefGoogle Scholar
  42. 42.
    Subach BR, Witham TF, Kondziolka D, et al. Morbidity and survival after 1,3-bis(2-chloroethyl)-1-nitrosourea wafer implantation for recurrent glioblastoma: a retrospective case-matched cohort series. Neurosurgery 1999; 45:17–22.PubMedCrossRefGoogle Scholar
  43. 43.
    LaRocca R, Hodes J, Villanueva W, et al. A phase II study of radiation with concomitant and then sequential temozolomide (TMZ) in patients with newly diagnosed supratentorial high-grade malignant glioma who have undergone surgery with carmustine (BCNU) wafer insertion. Presented at the 11th Scientific Meeting of the Society for Neuro-Oncology, 2006Google Scholar

Copyright information

© Society of Surgical Oncology 2008

Authors and Affiliations

  • Frank J. Attenello
    • 1
  • Debraj Mukherjee
    • 1
  • Ghazala Datoo
    • 1
  • Matthew J. McGirt
    • 1
    Email author
  • Eileen Bohan
    • 1
  • Jon D. Weingart
    • 1
  • Alessandro Olivi
    • 1
  • Alfredo Quinones-Hinojosa
    • 1
  • Henry Brem
    • 1
  1. 1.Department of NeurosurgeryJohns Hopkins School of MedicineBaltimoreUSA

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