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.
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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.
This article does not contain any studies with human participants performed by any of the authors.
This article was written after obtaining patient’s consent.
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
Tolcher AW, Gerson SL, Denis L et al (2003) Marked inactivation of O6-alkylguanine-DNA alkyltransferase activity with protracted temozolomide schedules. Br J Cancer 88:1004–1011CrossRefPubMedPubMedCentralGoogle Scholar
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
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
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
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
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
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
Villano JL, Seery TE, Bressler LR (2009) Temozolomide in malignant gliomas: current use and future targets. Cancer Chemother Pharmacol 64:647–655CrossRefPubMedGoogle Scholar
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
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
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