Skip to main content
SpringerLink
Log in

Drugs for Primary Brain Tumors: An Update

  • Chapter
  • First Online:
Tumors of the Central Nervous System, Volume 12

Part of the book series: Tumors of the Central Nervous System ((TCNS,volume 12))

Abstract

Primary brain tumors are a heterogeneous mix of tumors that can arise from structures within the cranium. This review will focus on tumors of glial origin. The best first approach to a primary brain tumor is maximal safe surgical resection. If the tumor is not amenable to resection, a biopsy is needed for tissue diagnosis. Despite maximal resection of the tumor, there always remains residual disease due to the infiltrative nature of the tumor. This has led to development of various chemotherapeutic regimens which have been developed for use in the neo-adjuvant, adjuvant and recurrent setting. The most significant development of these tumors is for high grade gliomas. Anaplastic astrocytomas and glioblastoma multiforme are frequently diagnosed tumors that continue to have a poor prognosis and short survival. Historically, chemotherapy has been demonstrated to provide a marginal survival benefit in patients with anaplastic astrocytoma and glioblastoma multiforme when used after surgical resection and radiation therapy. Modest improvement in overall survival was initially seen with the use of nitrosurea drugs, such as BCNU and CCNU, as well as some platinum compounds. More recent data suggests the use of temozolomide (TMZ) leads to an improved overall survival when given concurrently with radiation following resection of these aggressive tumors. Data on the vascular endothelial growth factor (VEGF) inhibitor, bevacizumab, has also been available and will be presented in the preceding text. Chemotherapeutic agents had a less pivotal role in the setting of low grade astrocytomas and other primary brain tumors.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Abrey LE, Childs BH, Paleologos N, Kaminer L, Rosenfeld S, Salzman D, Finlay JL, Gardner S, Peterson K, Hu W, Swinnen L, Bayer R, Forsyth P, Stewart D, Smith AM, Macdonald DR, Weaver S, Ramsay DA, Nimer SD, DeAngelis LM, Cairncross JG (2006) High-dose chemotherapy with stem cell rescue as initial therapy for anaplastic oligodendroglioma: long-term follow-up. Neuro Oncol 8:183–188

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Abrey LE, Louis DN, Paleologos N, Lassman AB, Raizer JJ, Mason W, Finlay J, MacDonald DR, DeAngelis LM, Cairncross JG (2007) Survey of treatment recommendations for anaplastic oligodendroglioma. Neuro Oncol 9:314–318

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Batchelor TT, Gilbert MR, Supko JG, Carson KA, Nabors LB, Grossman SA, Lesser GJ, Mikkelsen T, Phuphanich S (2004) Phase 2 study of weekly irinotecan in adults with recurrent malignant glioma: final report of NABTT 97–11. Neuro Oncol 6:21–27

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Brem H, Piantadosi S, Burger PC, Walker M, Selker R, Vick NA, Black K, Sisti M, Brem S, Mohr G, Muller P, Morawetz R, Schold SC (1995) 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 345:1008–1012

    Article  CAS  PubMed  Google Scholar 

  • Butowski NA, Sneed PK, Chang SM (2006) Diagnosis and treatment of recurrent high-grade astrocytoma. J Clin Oncol 24:1273–1280

    Article  CAS  PubMed  Google Scholar 

  • Cairncross JG, Macdonald DR (1988) Successful chemotherapy for recurrent malignant oligodendroglioma. Ann Neurol 23:360–364

    Article  CAS  PubMed  Google Scholar 

  • Cairncross G, Berkey B, Shaw E, Jenkins R, Scheithauer B, Brachman D, Buckner J, Fink K, Souhami L, Laperierre N, Mehta M, Curran W (2006) 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 18:2707–2714

    Article  Google Scholar 

  • Cairncross JG, Wang M, Edward S, Jenkins R, Scheithauer BW, Brachman D, Buckner JC, Fink KL, Souhami L, Laperriere N, Walter WJ, Mehta MP (2012) Chemotherapy plus radiotherapy (CT-RT) versus RT alone for patients with anaplstic oligodendroglioma: long term results of RTOG 9402 phase III study. J Clin Oncol 31(3):337–343

    Google Scholar 

  • Chamberlain MC, Chalmers L (2007) A pilot study of primary temozolomide chemotherapy and deferred radiotherapy in elderly patients with glioblastoma. J Neurooncol 82:207–209

    Article  PubMed  Google Scholar 

  • Colevas AD, Brown JM, Hahn S, Mitchell J, Camphausen K, Coleman CN (2003) Development of investigational radiation modifiers. J Natl Cancer Inst 95:646–651

    Article  CAS  PubMed  Google Scholar 

  • Desjardins A, Reardon DA, Coan A, Macello J, Herndon JE, Bailey L, Peters KB, Friedman HD, Vredenburgh JJ (2012) Bevacizumab and daily temozolomide for recurrent glioblastoma. Cancer 118:1302–1312

    Article  CAS  PubMed  Google Scholar 

  • Esteller M, Garcia-Foncillas J, Andion E, Goodman SN, Hidalgo OF, Vanaclocha V, Baylin SB, Herman JG (2000) Inactivation of the DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents. N Engl J Med 343:1350–1354

    Article  CAS  PubMed  Google Scholar 

  • Fetell MR, Grossman SA, Fisher JD, Erlanger B, Rowinsky E, Stockel J, Piantadosi S (1997) Preirradiation paclitaxel in glioblastoma multiforme: efficacy, pharmacology, and drug interactions. New Approaches to Brain Tumor Therapy Central Nervous System Consortium. J Clin Oncol 15:3121–3128

    CAS  PubMed  Google Scholar 

  • Fine HA, Dear KB, Loeffler JS, Black PM, Canellos GP (1993) Meta-analysis of radiation therapy with and without adjuvant chemotherapy for malignant gliomas in adults. Cancer 71:2585–2597

    Article  CAS  PubMed  Google Scholar 

  • Friedman HS, McLendon RE, Kerby T, Dugan M, Bigner SH, Henry AJ, Ashley DM, Krischer J, Lovell S, Rasheed K, Marchev F, Seman AJ, Cokgor I, Rich J, Stewart E, Colvin OM, Provenzale JM, Bigner DD, Haglund MM, Friedman AH, Modrich PL (1998) DNA mismatch repair and O6-alkylguanine-DNA alkyltransferase analysis and response to Temodal in newly diagnosed malignant glioma. J Clin Oncol 16:3851–3857

    CAS  PubMed  Google Scholar 

  • Friedman HS, Prados MD, Wen PY, Mikkelsen T, Schiff D, Abrey LE, Yung WK, Paleologos N, Nicholas MK, Jensen R, Vredenburgh J, Huang J, Zheng M, Cloughesy T (2009) Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol 27:4733–4740

    Article  CAS  PubMed  Google Scholar 

  • Gilbert MR, Wang M, Aldape KD, Stupp R, Hegi M, Jaeckle KA, Armstrong TS, Wefel JS, Won M, Blumenthal DT, Mahajan A, Schultz CJ, Erridge SC, Brown PD, Chakravarti A, Curran WJ, Mehta MP (2011) RTOG 0525: a randomized phase III trial comparing standard adjuvant temozolomide (TMZ) with a dose-dense (dd) schedule in newly diagnosed glioblastoma (GBM). J Clin Oncol 29(suppl; abstr 2006)

    Google Scholar 

  • Grossman SA, Ye X, Piantadosi S, Desideri S, Nabors LB, Rosenfeld M, Fisher J (2010) Survival of patients with newly diagnosed glioblastoma treated with radiation and temozolomide in research studies in the United States. Clin Cancer Res 16:2443–2449

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Hegi ME, Diserens AC, Gorlia T, Hamou MF, de Tribolet N, Weller M, Kros JM, Hainfellner JA, Mason W, Mariani L, Bromberg JE, Hau P, Mirimanoff RO, Cairncross JG, Janzer RC, Stupp R (2005) MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352:997–1003

    Article  CAS  PubMed  Google Scholar 

  • Jaeckle KA, Eyre HJ, Townsend JJ, Schulman S, Knudson HM, Belanich M, Yarosh DB, Bearman SI, Giroux DJ, Schold SC (1998) Correlation of tumor O6 methylguanine-DNA methyltransferase levels with survival of malignant astrocytoma patients treated with bis-chloroethylnitrosourea: a Southwest Oncology Group study. J Clin Oncol 16:3310–3315

    CAS  PubMed  Google Scholar 

  • Jemal A, Siegel R, Xu J, Ward E (2010) Cancer statistics, 2010. CA Cancer J Clin 60:277–300

    Article  PubMed  Google Scholar 

  • Kreisl TN, Kim L, Moore K, Duic P, Royce C, Stroud I, Garren N, Mackey M, Butman JA, Camphausen K, Park J, Albert PS, Fine HA (2009) Phase II trial of single-agent bevacizumab followed by bevacizumab plus irinotecan at tumor progression in recurrent glioblastoma. J Clin Oncol 27:740–745

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Laperriere N, Zuraw L, Cairncross G (2002) Radiotherapy for newly diagnosed malignant glioma in adults: a systematic review. Radiother Oncol 64:259–273

    Article  PubMed  Google Scholar 

  • Perry JR, Belanger K, Mason WP, Fulton D, Kavan P, Easaw J, Shields C, Kirby S, Macdonald DR, Eisenstat DD, Thiessen B, Forsyth P, Pouliot JF (2010) Phase II trial of continuous dose-intense temozolomide in recurrent malignant glioma: RESCUE study. J Clin Oncol 28:2051–2057

    Article  CAS  PubMed  Google Scholar 

  • Prados MD, Scott C, Curran WJ, Nelson DF, Leibel S, Kramer S (1999) Procarbazine, lomustine, and vincristine (PCV) chemotherapy for anaplastic astrocytoma: a retrospective review of radiation therapy oncology group protocols comparing survival with carmustine or PCV adjuvant chemotherapy. J Clin Oncol 17(11)):3389–3395

    CAS  PubMed  Google Scholar 

  • Prados MD, Lamborn K, Yung WK, Jaeckle K, Robins HI, Mehta M, Fine HA, Wen PY, Cloughesy T, Chang S, Nicholas MK, Schiff D, Greenberg H, Junck L, Fink K, Hess K, Kuhn J (2006) A phase 2 trial of irinotecan (CPT-11) in patients with recurrent malignant glioma: a North American Brain Tumor Consortium study. Neuro Oncol 8:189–193

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Reardon DA, Desjardins A, Vredenburgh JJ, Gururangan S, Sampson JH, Sathornsumetee S, McLendon RE, Marcello JE, Norfleet J, Friedman AH, Bigner DD, Friedman HS (2009) Metronomic chemotherapy with daily, oral etoposide plus bevacizumab for recurrent malignant glioma: a phase II study. Br J Cancer 101:1986–1994

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Reardon DA, Desjardins A, Peters KB, Guruangan S, Sampson JH, McLendon RE, Herndon JE, Bulusu A, Threatt S, Friedman AH, Vredenburgh JJ, Friedman HS (2012) Phase II study of carboplatin, irinotecan, and bevacizumab for bevacizumab naive, recurrent glioblastoma. J Neurooncol 107:155–164

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Sathornsumetee S, Desjardins A, Vredenburgh JJ, McLendon RE, Marcello J, Herndon JE, Mathe A, Hamilton M, Rich JN, Norfleet JA, Gururangan S, Friedman HS, Reardon DA (2010) Phase II trial of bevacizumab and erlotinib in patients with recurrent malignant glioma. Neuro Oncol 12:1300–1310

    CAS  PubMed Central  PubMed  Google Scholar 

  • Smith JS, Perry A, Borell TJ, Lee HK, O’Fallon J, Hosek SM, Kimmel D, Yates A, Burger PC, Scheithauer BW, Jenkins RB (2000) Alterations of chromosome arms 1p and 19q as predictors of survival in oligodendrogliomas, astrocytomas, and mixed oligoastrocytomas. J Clin Oncol 18:636–645

    CAS  PubMed  Google Scholar 

  • Stern JI, Raizer JJ (2006) Chemotherapy in the treatment of malignant gliomas. Expert Rev Anticancer Ther 6:755–767

    Article  CAS  PubMed  Google Scholar 

  • Stewart LA (2002) Chemotherapy in adult high-grade glioma: a systematic review and meta-analysis of individual patient data from 12 randomised trials. Lancet 359:1011–1018

    Article  CAS  PubMed  Google Scholar 

  • Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996

    Article  CAS  PubMed  Google Scholar 

  • van den Bent MJ, Carpentier AF, Brandes AA, Sanson M, Taphoorn MJ, Bernsen HJ, Frenay M, Tijssen CC, Grisold W, Sipos L, Haaxma-Reiche H, Kros JM, van Kouwenhoven MC, Vecht CJ, Allgeier A, Lacombe D, Gorlia T (2006) Adjuvant prcarbacine, lomustine, and vincristine improves progression-free survival but not overall survivial in newly diagnosed anaplastic oligodendrogliomas and oligoastrocytomas: a randomized European Organization for Research and Treatment of Cancer phase III trial. J Clin Oncol 18:2715–2722

    Article  Google Scholar 

  • van den Bent MJ, Hoang-Xuan K, Brandes AA, Kros J, Kouwenhoven M, Taphoorn M, Delattre JY, Bernsen H, Frenay M, Tijssen C, Grisold W, Sipos L, Enting R, Dinjens W, French P, Vecht C, Allgeier A, Lacombe D, Gorlia T (2012) Long-term follow-up results of EORTC 26951: a randomized phase III study on adjuvant PCV chemotherapy in anaplstic oligodendroglial tumors (AOD). J Clin Oncol 30:344–350

    Google Scholar 

  • Walker MD, Alexander J, Hunt WE, MacCarty CS, Mahaley MS, Mealey J, Norrell HA, Owens G, Ransohoff J, Wilson CB, Gehan EA, Strike TA (1978) Evaluation of BCNU and/or radiotherapy in the treatment of anaplastic gliomas: a cooperative clinical trial. J Neurosurg 49:333–343

    Article  CAS  PubMed  Google Scholar 

  • Walker MD, Green SB, Byar DP, Alexander E Jr, Batzdorf U, Brooks WH, Hunt WE, MacCarty CS, Mahaley MS Jr, Mealey J Jr, Owens G, Ransohoff J, Robertson JT, Shapiro WR, Smith KR Jr, Wilson CB, Strike TA (1980) Randomized comparisons of radiotherapy and nitrosoureas for the treatment of malignant glioma after surgery. N Engl J Med 303:1323–1329

    Article  CAS  PubMed  Google Scholar 

  • Westphal M, Ram Z, Riddle V, Hilt D, Bortey E (2006) Gliadel wafer in initial surgery for malignant glioma: long-term follow-up of a multicenter controlled trial. Acta Neurochir (Wien) 148:269–275, discussion 275

    Article  CAS  Google Scholar 

  • Wick W, Hartmann C, Engel C, Stoffels M, Felsberg J, Stockhammer F, Sabel MC, Koeppen S, Ketter R, Meyermann R, Rapp M, Meisner C, Kortmann RD, Pietsch T, Wiestler OD, Ernemann U, Bamberg M, Reifenberger G, von Diemling A, Weller M (2009) NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplstic glioma with procarbazine, lomustine, and vincristine or temozolomide. J Clin Oncol 35:5874–5880

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine, Section Hematology/Oncology, Northwestern University, 251 East Huron Street, Galter Suite 3-150, Chicago, IL, 60611, USA

    Lauren Nye & Timothy Huyck

  2. Department of Medicine, Medical Neuro-Oncology, Northwestern University, 710 North Lake Shore Dr. Abbott Hall, Room 1123, Chicago, IL, 60611, USA

    Jeffrey Raizer

Authors
  1. Lauren Nye
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Timothy Huyck
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jeffrey Raizer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jeffrey Raizer .

Editor information

Editors and Affiliations

  1. Department of Biological Sciences, Kean University, Room 213, Library Building, Union, New Jersey, USA

    M.A. Hayat

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

Nye, L., Huyck, T., Raizer, J. (2014). Drugs for Primary Brain Tumors: An Update. In: Hayat, M. (eds) Tumors of the Central Nervous System, Volume 12. Tumors of the Central Nervous System, vol 12. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-7217-5_25

Download citation

  • DOI: https://doi.org/10.1007/978-94-007-7217-5_25

  • Published:

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-94-007-7216-8

  • Online ISBN: 978-94-007-7217-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation