Skip to main content
SpringerLink
Log in

Nitrosoureas in the Management of Malignant Gliomas

  • Neuro-oncology (L. E. Abrey, Section Editor)
  • Published:
Current Neurology and Neuroscience Reports Aims and scope Submit manuscript

Abstract

Nitrosoureas represent one of the most active classes of agents in the treatment of high-grade gliomas and glioblastoma. In clinical practice, the most commonly used compounds are lomustine (either alone or in combination with procarbazine and vincristine), carmustine, and fotemustine. Given their toxicity profile and subsequent to the introduction of temozolomide in clinical practice, most of these agents were moved to the recurrent setting. This review focuses on the role of the nitrosoureas currently used in clinical practice for the treatment of malignant gliomas.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. DeVita VT, et al. Rosenberg, Steven A. Devita, Hellman, and Rosenberg’s cancer: principles & practice of oncology. Philadelphia: Wolters Kluwer. Second edition. Pp 372–373

  2. 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(9311):1011–8. Meta-analysis showing the survival improvement obtained with nitrosoureas in newly-diagnosed high-grade gliomas.

    Article  CAS  PubMed  Google Scholar 

  3. 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. Randomized trial that showed the survival advantage of BCNU plus RT over RT alone in newly-diagnosed GBM.

    Article  CAS  PubMed  Google Scholar 

  4. Brandes AA et al. Early chemotherapy and concurrent radio-chemotherapy in high grade glioma. J Neurooncol. 1996;30(3):247–55.

    Article  CAS  PubMed  Google Scholar 

  5. van den Bent MJ et al. Randomized phase II trial of erlotinib versus temozolomide or carmustine in recurrent glioblastoma: EORTC brain tumor group study 26034. J Clin Oncol. 2009;27(8):1268–74.

    Article  PubMed Central  PubMed  Google Scholar 

  6. Brandes AA et al. How effective is BCNU in recurrent glioblastoma in the modern era? A phase II trial. Neurology. 2004;63(7):1281–4.

    Article  CAS  PubMed  Google Scholar 

  7. Reithmeier T et al. BCNU for recurrent glioblastoma multiforme: efficacy, toxicity and prognostic factors. BMC Cancer. 2010;10:30.

    Article  PubMed Central  PubMed  Google Scholar 

  8. Brandes AA et al. Second-line chemotherapy with irinotecan plus carmustine in glioblastoma recurrent or progressive after first-line temozolomide chemotherapy: a phase II study of the Gruppo Italiano Cooperativo di Neuro-Oncologia (GICNO). J Clin Oncol. 2004;22(23):4779–86.

    Article  CAS  PubMed  Google Scholar 

  9. Levin VA et al. Nitrosourea chemotherapy for primary malignant gliomas. Cancer Treat Rep. 1976;60:719–24.

    CAS  PubMed  Google Scholar 

  10. Shapiro WR et al. Chemotherapy of malignant glioma with CCNU alone and CCNU combined with vincristine sulfate and procarbazine hydrochloride. Trans Am Neurol Assoc. 1976;101:217–20.

    CAS  PubMed  Google Scholar 

  11. E.O.R.T.C. Brain Tumor Group. Effect of CCNU on survival rate of objective remission and duration of free interval in patients with malignant brain glioma--final evaluation. Eur J Cancer. 1978;14(8):851–6.

    Article  Google Scholar 

  12. Eyre HJ et al. Randomized comparisons of radiotherapy and CCNU versus radiotherapy, CCNU plus procarbazine for the treatment of malignant gliomas following surgery. A Southwest Oncology Group Report. J Neurooncol. 1983;1(3):171–7.

    Article  CAS  PubMed  Google Scholar 

  13. Levin VA. Chemotherapy of primary brain tumors. In: Frank BD, editor. Symposium on Neuro-oncology, vol 3, Neurologic Clinics. 4th ed. York, Penn: WB Saunders; 1985. p. 855–66.

    Google Scholar 

  14. Levin VA et al. Superiority of post-radiotherapy adjuvant chemotherapy with CCNU, procarbazine, and vincristine (PCV) over BCNU for anaplastic gliomas: NCOG 6G61 final report. J Radiat Oncol Biol Phys. 1990;18:321–4. This study showed the survival advantage of PCV over BCNU as post-RT adjuvant therapy in high-grade gliomas.

    Article  CAS  Google Scholar 

  15. Levin VA et al. Superiority of post-radiotherapy adjuvant chemotherapy with CCNU, procarbazine, and vincristine (PCV) over BCNU for anaplastic gliomas: NCOG 6G61 final report. J Radiat Oncol Biol Phys. 1990;18:321–4.

    Article  CAS  Google Scholar 

  16. Stupp R et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352:987–96.

    Article  CAS  PubMed  Google Scholar 

  17. Wick W, Puduvalli VK, Chamberlain MC, et al. Phase III study of enzastaurin compared with lomustine in the treatment of recurrent intracranial glioblastoma. J Clin Oncol. 2010;28(7):1168–74.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. Batchelor T et al. The efficacy of cediranib as monotherapy and in combination with lomustine compared to lomustine alone in patients with recurrent glioblastoma: a phase III randomized trial. J Clin Oncol. 2013;31:3212–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Taal W et al. Single-agent bevacizumab or lomustine versus a combination of bevacizumab plus lomustine in patients with recurrent glioblastoma (BELOB trial): a randomised controlled phase 2 trial. Lancet Oncol. 2014;15:943–53.

    Article  CAS  PubMed  Google Scholar 

  20. Brandes AA et al. Fotemustine as second-line treatment for recurrent or progressive glioblastoma after concomitant and/or adjuvant temozolomide: a phase II trial of Gruppo Italiano Cooperativo di Neuro-Oncologia (GICNO). Cancer Chemother Pharmacol. 2009;64(4):769–75. This study showed the activity of fotemustine in recurrent GBM.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Addeo R et al. A new schedule of fotemustine in temozolomide-pretreated patients with relapsing glioblastoma. J Neurooncol. 2011;102(3):417–24.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Brandes A et al. Randomized phase II trial AVAREG (ML25739) with bevacizumab (BEV) or fotemustine (FTM) in recurrent glioblastoma: final results from the randomized phase II trial. Ann Oncol. 2014;25 suppl 4:iv137.

    Google Scholar 

  23. Cairncross G et al. Phase III trial of chemotherapy plus radiotherapy compared with radiotherapy alone for pure and mixed anaplastic oligodendroglioma: Intergroup Radiation Therapy Oncology Group Trial 9402. J Clin Oncol. 2006;24:2707–14.

    Article  CAS  PubMed  Google Scholar 

  24. van den Bent MJ et al. Adjuvant procarbazine, lomustine, and vincristine improves progression-free survival but not overall survival in newly diagnosed anaplastic oligodendrogliomas and oligoastrocytomas: a randomized European Organisation for Research and Treatment of Cancer phase III trial. J Clin Oncol. 2006;24:2715–22.

    Article  PubMed  Google Scholar 

  25. Wick W et al. NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with procarbazine, lomustine, and vincristine or temozolomide. J Clin Oncol. 2009;27(35):5874–80. A randomized phase III trial that compares upfront treatment with RT or chemotherapy (PCV or temozolomide) in anaplastic gliomas.

    Article  CAS  PubMed  Google Scholar 

  26. Cairncross G et al. Phase III trial of chemoradiotherapy for anaplastic oligodendroglioma: long-term results of RTOG 9402. J Clin Oncol. 2013;31(3):337–43. A randomized phase III trial that compared RT alone versus RT plus PCV as adjuvant treatment for AOD and AOA.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. van den Bent MJ et al. Adjuvant procarbazine, lomustine, and vincristine chemotherapy in newly diagnosed anaplastic oligodendroglioma: long-term follow-up of EORTC brain tumor group study 26951. J Clin Oncol. 2013;31(3):344–50. This study showed an advantage in OS with the addition of PCV to standard radiotherapy in AO and AOA.

    Article  PubMed  Google Scholar 

  28. van den Bent MJ et al. MGMT promoter methylation is prognostic but not predictive for outcome to adjuvant PCV chemotherapy in anaplastic oligodendroglial tumors: a report from EORTC Brain Tumor Group Study 26951. J Clin Oncol. 2009;27(35):5881–6.

    Article  PubMed Central  PubMed  Google Scholar 

  29. van den Bent MJ et al. IDH1 and IDH2 mutations are prognostic but not predictive for outcome in anaplastic oligodendroglial tumors: a report of the European Organization for Research and Treatment of Cancer Brain Tumor Group. Clin Cancer Res. 2010;16(5):1597–604.

    Article  PubMed  Google Scholar 

  30. Wick W, et al. Long-term analysis of the NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with PCV or temozolomide. J Clin Oncol. 2015;33(suppl; abstr 2001)

  31. Cairncross G et al. Chemotherapy for anaplastic oligodendroglioma. National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 1994;12:2013–21.

    CAS  PubMed  Google Scholar 

  32. van den Bent MJ et al. Response rate and prognostic factors of recurrent oligodendroglioma treated with procarbazine, CCNU, and vincristine chemotherapy. Dutch Neuro-Oncol Group Neurol. 1998;51:1140–5.

    Google Scholar 

  33. Brada M et al. Temozolomide versus procarbazine, lomustine, and vincristine in recurrent high-grade glioma. J Clin Oncol. 2010;28(30):4601–8. A trial comparing temozolomide versus PCV in recurrent high-grade gliomas.

    Article  CAS  PubMed  Google Scholar 

  34. Fernández-Hidalgo OA et al. High-dose BCNU and autologous progenitor cell transplantation given with intra-arterial cisplatinum and simultaneous radiotherapy in the treatment of high-grade gliomas: benefit for selected patients. Bone Marrow Transplant. 1996;18(1):143–9.

    PubMed  Google Scholar 

  35. Jakacki RI et al. Dose-intensive, time-compressed procarbazine, CCNU, vincristine (PCV) with peripheral blood stem cell support and concurrent radiation in patients with newly diagnosed high-grade gliomas. J Neurooncol. 1999;44(1):77–83.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medical Oncology, Bellaria Hospital, Azienda USL - IRCCS Institute of Neurological Sciences, Via Altura 3, 40139, Bologna, Italy

    Alba A. Brandes, Marco Bartolotti, Alicia Tosoni & Enrico Franceschi

Authors
  1. Alba A. Brandes
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marco Bartolotti
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alicia Tosoni
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Enrico Franceschi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alba A. Brandes.

Ethics declarations

Conflict of Interest

Alba A. Brandes, Marco Bartolotti, Alicia Tosoni, and Enrico Franceschi each declare no potential conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Neuro-oncology

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Brandes, A.A., Bartolotti, M., Tosoni, A. et al. Nitrosoureas in the Management of Malignant Gliomas. Curr Neurol Neurosci Rep 16, 13 (2016). https://doi.org/10.1007/s11910-015-0611-8

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11910-015-0611-8

Keywords

Search

Navigation