Cancer Chemotherapy and Pharmacology

, Volume 80, Issue 5, pp 1043–1046 | Cite as

Long-term daily temozolomide with dose-dependent efficacy in MGMT promotor methylation negative recurrent high-grade astrocytoma

  • Zhengqiu Zhou
  • Tracy A. Howard
  • John L. Villano
Short Communication


Temozolomide (TMZ) for malignant gliomas is traditionally dosed in 5 out of a 28-day cycle, however alternative regimens exist, including dose-dense. Continuous daily dosing is available, but the acceptable dose and duration of therapy is unknown. We document a 40-year-old male with recurrent anaplastic astrocytoma, IDH mutant and MGMT promotor methylation negative, who has well-tolerated continuous daily TMZ for 20 months at 100 mg per day for nearly the length of this period. A trial at 80 mg per day demonstrated disease progression with response upon return to 100 mg per day. Prior to the daily TMZ, the patient underwent three surgical resections, radiation therapy with concurrent TMZ according to the EORTC-NCIC protocol, and subsequently bevacizumab in combination with use of the Optune device. Long-term survival of patients with recurrent malignant gliomas is uncommon, and currently no standard treatment strategies exist for these patients. We present this case to demonstrate the tolerability and dose dependency of prolonged daily TMZ dosing as a therapeutic option for recurrent anaplastic astrocytomas.


Temozolomide Anaplastic astrocytoma Dose-dense High-grade astrocytoma Long-term daily dosing Dose dependence 



The authors would like to thank the patient and his family.

Compliance with ethical standards

Conflict of interest

There are no conflicts of interests from authors relating to treatments discussed within.

Ethical approval

This article does not contain any studies with human participants performed by any of the authors.



Informed consent

This article was written after obtaining patient’s consent.


  1. 1.
    Brada M, Hoang-Xuan K, Rampling R et al (2001) Multicenter phase II trial of temozolomide in patients with glioblastoma multiforme at first relapse. Ann Oncol 12:259–266CrossRefPubMedGoogle Scholar
  2. 2.
    Tolcher AW, Gerson SL, Denis L et al (2003) Marked inactivation of O 6-alkylguanine-DNA alkyltransferase activity with protracted temozolomide schedules. Br J Cancer 88:1004–1011CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Kong DS, Lee JI, Kim JH et al (2010) Phase II trial of low-dose continuous (metronomic) treatment of temozolomide for recurrent glioblastoma. Neuro Oncol 12:289–296CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Perry JR, Belanger K, Mason WP et al (2010) Phase II trial of continuous dose-intense temozolomide in recurrent malignant glioma: RESCUE study. J Clin Oncol 28:2051–2057CrossRefPubMedGoogle Scholar
  5. 5.
    Norden AD, Lesser GJ, Drappatz J et al (2013) Phase 2 study of dose-intense temozolomide in recurrent glioblastoma. Neuro Oncol 15:930–935CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Omuro A, Chan TA, Abrey LE et al (2013) Phase II trial of continuous low-dose temozolomide for patients with recurrent malignant glioma. Neuro Oncol 15:242–250CrossRefPubMedGoogle Scholar
  7. 7.
    Louis DN, Ohgaki H, Wiestler OD, Cavenee WK (2016) WHO classification of tumours of the central nervous system, revised 4th edn. World Health Organization, LyonGoogle Scholar
  8. 8.
    Wen PY, Macdonald DR, Reardon DA et al (2010) Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. J Clin Oncol 28:1963–1972CrossRefPubMedGoogle Scholar
  9. 9.
    Mamlouk MD, Handwerker J, Ospina J et al (2013) Neuroimaging findings of the post-treatment effects of radiation and chemotherapy of malignant primary glial neoplasms. Neuroradiol J 26:396–412CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Villano JL, Seery TE, Bressler LR (2009) Temozolomide in malignant gliomas: current use and future targets. Cancer Chemother Pharmacol 64:647–655CrossRefPubMedGoogle Scholar
  11. 11.
    Woo JY, Yang SH, Lee YS et al (2015) Continuous low-dose temozolomide chemotherapy and microvessel density in recurrent glioblastoma. J Korean Neurosurg Soc 58:426–431CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Kanzawa T, Germano IM, Komata T et al (2004) Role of autophagy in temozolomide-induced cytotoxicity for malignant glioma cells. Cell Death Differ 11:448–457CrossRefPubMedGoogle Scholar
  13. 13.
    Kerbel RS, Kamen BA (2004) The anti-angiogenic basis of metronomic chemotherapy. Nat Rev Cancer 4:423–436CrossRefPubMedGoogle Scholar
  14. 14.
    Gilbert MR, Wang M, Aldape KD et al (2013) Dose-dense temozolomide for newly diagnosed glioblastoma: a randomized phase III clinical trial. J Clin Oncol 31:4085–4091CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Brennan CW, Verhaak RG, McKenna A et al (2013) The somatic genomic landscape of glioblastoma. Cell 155:462–477CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Hegi ME, Diserens AC, Gorlia T et al (2005) MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352:997–1003CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  1. 1.Markey Cancer CenterUniversity of KentuckyLexingtonUSA
  2. 2.Departments of Medicine, Neurosurgery, and NeurologyUniversity of KentuckyLexingtonUSA

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