Annals of Surgical Oncology

, Volume 17, Issue 7, pp 1740–1746

Biodegradable Carmustine Wafers (Gliadel) Alone or in Combination with Chemoradiotherapy: The French Experience

  • Philippe Menei
  • Philippe Metellus
  • Elsa Parot-Schinkel
  • Hugues Loiseau
  • Laurent Capelle
  • Guy Jacquet
  • Jacques Guyotat
  • The Neuro-oncology Club of the French Society of Neurosurgery
Neuro-Oncology

Abstract

Background

Carmustine-releasing wafers (Gliadel®) have been available and reimbursed in France since 2005.

Methods

A retrospective multicenter study was conducted in 26 French Departments of Neurosurgery to analyze practices of French neurosurgeons using Gliadel, compare the adverse effects and survival with those of previous phase III trials, and assess survival in patients with newly diagnosed malignant gliomas (MG) receiving Gliadel plus radiochemotherapy with temozolomide (TMZ). A total of 163 patients who received Gliadel for MG were included in this study: 83 (51%) with newly diagnosed MG and 80 (49%) with recurrent MG. In the newly diagnosed group, 51.8% of patients received radiochemotherapy with TMZ.

Results

Adverse events (AEs) emerged in 44.6% of the population, including 6% with septic abscess. The AE rate was not statistically correlated with adjuvant use of TMZ. For the newly diagnosed group, median survival was 17 months. Total or subtotal resection appeared to have a great impact on survival (P = 0.016), as did treatment with adjuvant radiotherapy (P = 0.004).

For the group with recurrent MG, median survival was 7 months. Total or subtotal resection excision appeared to have a great impact on survival (P = 0.002), as did preoperative Karnowsky Scale (PO-KPS) (P = 0.012).

Conclusions

Survival rates for newly diagnosed patients were better than those reported in previous phase III trials. The combination of Gliadel and radiochemotherapy with TMZ was well tolerated and appeared to increase survival without increasing AEs.

References

  1. 1.
    Surawicz TS, et al. Descriptive epidemiology of primary brain and CNS tumors: results from the Central Brain Tumor Registry of the United States, 1990–1994. Neuro Oncol. 1999;1(1):14–25.PubMedGoogle Scholar
  2. 2.
    Walker MD, et al. Randomized comparisons of radiotherapy and nitrosoureas for the treatment of malignant glioma after surgery. N Engl J Med. 1980;303(23):1323–9.PubMedCrossRefGoogle Scholar
  3. 3.
    Fine HA, et al. Meta-analysis of radiation therapy with and without adjuvant chemotherapy for malignant gliomas in adults. Cancer. 1993;71(8):2585–97.CrossRefPubMedGoogle Scholar
  4. 4.
    Brem H, 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(8956):1008–12.CrossRefPubMedGoogle Scholar
  5. 5.
    Westphal M, 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.CrossRefPubMedGoogle Scholar
  6. 6.
    Westphal M, et al. Gliadel wafer in initial surgery for malignant glioma: long-term follow-up of a multicenter controlled trial. Acta Neurochir (Wien). 2006;148(3):269–75.CrossRefGoogle Scholar
  7. 7.
    Stupp R, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352(10):987–96.CrossRefPubMedGoogle Scholar
  8. 8.
    LaRocca RV, et al. A phase 2 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 [abstract]. Neuro Oncol. 2006;8(4):445.Google Scholar
  9. 9.
    Sarkaria JN, et al. Mechanisms of chemoresistance to alkylating agents in malignant glioma. Clin Cancer Res. 2008;14(10):2900–8.CrossRefPubMedGoogle Scholar
  10. 10.
    Daumas-Duport C, et al. [Gliomas: WHO and Sainte-Anne Hospital classifications]. Ann Pathol. 2000;20(5):413–28.PubMedGoogle Scholar
  11. 11.
    Rich JN, et al. Overall survival of primary glioblastoma (GBM) patients receiving carmustine (BCNU) wafers followed by radiation (RT) and concurrent temozolomide (TMZ) plus rotational multi-agent chemotherapy [abstract]. J Clin Oncol. 2007;25:2070.Google Scholar
  12. 12.
    Lawson HC, et al. Interstitial chemotherapy for malignant gliomas: the Johns Hopkins experience. J Neurooncol. 2007;83(1):61–70.CrossRefPubMedGoogle Scholar
  13. 13.
    McGovern PC, et al. Risk factors for postcraniotomy surgical site infection after 1,3-bis (2-chloroethyl)-1-nitrosourea (Gliadel) wafer placement. Clin Infect Dis. 2003;36(6):759–65.CrossRefPubMedGoogle Scholar
  14. 14.
    Attenello FJ, et al. Use of Gliadel (BCNU) wafer in the surgical treatment of malignant glioma: a 10-year institutional experience. Ann Surg Oncol. 2008;15(10):2887–93.CrossRefPubMedGoogle Scholar
  15. 15.
    Engelhard HH, Tumor bed cyst formation after BCNU wafer implantation: report of two cases. Surg Neurol. 2000;53(3):220–4.CrossRefPubMedGoogle Scholar
  16. 16.
    Kleinberg LR, 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):1–9.CrossRefPubMedGoogle Scholar
  17. 17.
    McGirt MJ, et al. Management of tumor bed cysts after chemotherapeutic wafer implantation Report of four cases. J Neurosurg. 2002;96(5):941–5.CrossRefPubMedGoogle Scholar
  18. 18.
    Kapsalaki EZ, Gotsis ED, Fountas KN. The role of proton magnetic resonance spectroscopy in the diagnosis and categorization of cerebral abscesses. Neurosurg Focus. 2008;24(6):E7.CrossRefPubMedGoogle Scholar
  19. 19.
    Lai PH, et al. Brain abscess and necrotic brain tumor: discrimination with proton MR spectroscopy and diffusion-weighted imaging. AJNR Am J Neuroradiol. 2002;23(8):1369–77.PubMedGoogle Scholar
  20. 20.
    Gururangan S, et al. Phase I study of Gliadel wafers plus temozolomide in adults with recurrent supratentorial high-grade gliomas. Neuro Oncol. 2001;3(4):246–50.PubMedGoogle Scholar
  21. 21.
    Subach BR, 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(1):17–22.CrossRefPubMedGoogle Scholar
  22. 22.
    Weber EL, Goebel EA. Cerebral edema associated with Gliadel wafers: two case studies. Neuro Oncol. 2005;7(1):84–9.CrossRefPubMedGoogle Scholar
  23. 23.
    Gallego JM, Barcia JA, Barcia-Marino C. Fatal outcome related to carmustine implants in glioblastoma multiforme. Acta Neurochir (Wien). 2007;149(3):261–5.CrossRefGoogle Scholar
  24. 24.
    Wu MP, et al. In vivo versus in vitro degradation of controlled release polymers for intracranial surgical therapy. J Biomed Mater Res. 1994;28(3):387–95.CrossRefPubMedGoogle Scholar
  25. 25.
    Darakchiev BJ, et al., Safety and efficacy of permanent iodine-125 seed implants and carmustine wafers in patients with recurrent glioblastoma multiforme. J Neurosurg. 2008;108(2):236–42.CrossRefPubMedGoogle Scholar
  26. 26.
    Limentani SA, 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(3):241–4.CrossRefPubMedGoogle Scholar
  27. 27.
    Weingart J, et al. Phase I trial of polifeprosan 20 with carmustine implant plus continuous infusion of intravenous O6-benzylguanine in adults with recurrent malignant glioma: new approaches to brain tumor therapy CNS consortium trial. J Clin Oncol. 2007;25(4):399–404.CrossRefPubMedGoogle Scholar
  28. 28.
    Vredenburgh JJ, et al. Phase II trial of bevacizumab and irinotecan in recurrent malignant glioma. Clin Cancer Res. 2007;13(4):1253–9.CrossRefPubMedGoogle Scholar

Copyright information

© Society of Surgical Oncology 2010

Authors and Affiliations

  • Philippe Menei
    • 1
  • Philippe Metellus
    • 2
  • Elsa Parot-Schinkel
    • 3
  • Hugues Loiseau
    • 4
  • Laurent Capelle
    • 5
  • Guy Jacquet
    • 6
  • Jacques Guyotat
    • 7
  • The Neuro-oncology Club of the French Society of Neurosurgery
  1. 1.Département de NeurochirurgieINSERM U646, CHU d’AngersAngersFrance
  2. 2.Service de NeurochirurgieHôpital de la TimoneMarseilleFrance
  3. 3.Centre de Recherche CliniqueCHU d’AngersAngersFrance
  4. 4.Clinique Universitaire de NeurochirurgieHôpital Pellegrin TripodeBordeauxFrance
  5. 5.Service de NeurochirurgieHôpital Pitié SalpétrièreParisFrance
  6. 6.Service de NeurochirurgieHôpital Jean MinjozBesançonFrance
  7. 7.Service de NeurochirurgieHôpital Neurologique Pierre WertheimerLyonFrance

Personalised recommendations