Abstract
Background: Patients with recurrent or progressive low grade gliomas survive for a decade or more following diagnosis, and may be at a higher risk for treatment-related complications, such as cognitive impairment from radiotherapy. Purpose: The aim of the present study was to determine in patients with progressive or recurrent low grade gliomas, the response rate and toxicity incurred by a continued schedule of temozolomide chemotherapy administered before radiation therapy, and to explore correlations between response and survival with 1p/19q deletions and MGMT promoter methylation status. Methods: Progressive radio and chemotherapy naïve low grade glioma patients with O6-methyl-guanine-DNA-methyl-tranferase (MGMT) promoter status evaluation were considered eligible. Chemotherapy cycles consisted of temozolomide 75 mg/m2/daily for 21 days every 28 days for 12 cycles. Results: A total of 30 patients (median age 45 [range: 24.2–68.6] years) with a median KPS of 90 (range 60–90) were accrued. The overall response rate was 30% (9 partial responses); 17 patients (56.7%) had disease stabilization. Conclusion: The prolonged temozolomide schedule considered in the present study is followed by a high response rate; toxicity is acceptable. Further randomized trials should therefore be conducted to confirm the efficacy of this regimen as first-line therapy in patients with progressive low grade glioma.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
CBTRUS, C.B.t.r.o.t.U.S. (2004) Primary brain tumors in the United States. Statistical report 1997–2001
Brandes AA, Tosoni A, Kortmann RD (2003) Guidelines for the management and treatment of low-grade gliomas. Forum (Genova) 13:4–17
Denny BJ, Wheelhouse RT, Stevens MF, Tsang LL, Slack JA (1994) NMR and molecular modeling investigation of the mechanism of activation of the antitumor drug temozolomide and its interaction with DNA. Biochemistry 33:9045–9051
Tolcher AW, Gerson SL, Denis L et al (2003) Marked inactivation of O6-alkylguanine-DNA alkyltransferase activity with protracted temozolomide schedules. Br J Cancer 88:1004–1011
Denis L, Tolcher A, Figueroa et al (2000) Protracted daily administration of temozolomide is feasible: a phase I and pharmacokinetic—pharmacodynamic study. In ASCO Proceedings, 2000 Annual Meeting, abstract number 786
Brandes AA, Tosoni A, Cavallo G et al (2006) Temozolomide 3 weeks on and 1 week off as first-line therapy for recurrent glioblastoma: phase II study from gruppo italiano cooperativo di neuro-oncologia (GICNO). Br J Cancer 95:1155–1160
Tosoni A, Cavallo G, Ermani M et al (2006) Is protracted low-dose temozolomide feasible in glioma patients? Neurology 66:427–429
Kovacs JA, Masur H (2000) Prophylaxis against opportunistic infections in patients with human immunodeficiency virus infection. N Engl J Med 342:1416–1429
Macdonald DR, Cascino TL, Schold SC Jr, Cairncross JG (1990) Response criteria for phase II studies of supratentorial malignant glioma. J Clin Oncol 8:1277–1280
Kaplan E, Meier P (1958) Non parametric estimation for incomplete observation. J Am Stat Assoc 53:457–481
Palmisano WA, Divine KK, Saccomanno G et al (2000) Predicting lung cancer by detecting aberrant promoter methylation in sputum. Cancer Res 60:5954–5958
van Engeland M, Weijenberg MP, Roemen GMJM et al (2003) Effects of dietary folate and alcohol intake on promoter methylation in sporadic colorectal cancer: the Netherlands cohort study on diet and cancer. Cancer Res 63:3133–3137
Simon R (1989) Designs for efficient clinical trials. Oncology (Huntingt) 3:43–49 discussion 51–43
Brada M, Viviers L, Abson C et al (2003) Phase II study of primary temozolomide chemotherapy in patients with WHO grade II gliomas. Ann Oncol 14:1715–1721
Hoang-Xuan K, Capelle L, Kujas M et al (2004) Temozolomide as initial treatment for adults with low-grade oligodendrogliomas or oligoastrocytomas and correlation with chromosome 1p deletions. J Clin Oncol 22:3133–3138
Pace A, Vidiri A, Galie E et al (2003) Temozolomide chemotherapy for progressive low-grade glioma: clinical benefits and radiological response. Ann Oncol 14:1722–1726
Hoang-Xuan K, He J, Huguet S, Mokhtari K et al (2001) Molecular heterogeneity of oligodendrogliomas suggests alternative pathways in tumor progression. Neurology 57:1278–1281
Quinn JA, Reardon DA, Friedman AH et al (2003) Phase II trial of temozolomide in patients with progressive low-grade glioma. J Clin Oncol 21:646–651
Mariani L, Deiana G, Vassella E et al (2006) Loss of heterozygosity 1p36 and 19q13 is a prognostic factor for overall survival in patients with diffuse WHO grade 2 gliomas treated without chemotherapy. J Clin Oncol 24:4758–4763
Kujas M, Lejeune J, Benouaich-Amiel A et al (2005) Chromosome 1p loss: a favorable prognostic factor in low-grade gliomas. Ann Neurol 58:322–326
Everhard S, Kaloshi G, Criniere E et al (2006) MGMT methylation: a marker of response to temozolomide in low-grade gliomas. Ann Neurol 60:740–743
Komine C, Watanabe T, Katayama Y, Yoshino A, Yokoyama T, Fukushima T (2003) Promoter hypermethylation of the DNA repair gene O6-methylguanine-DNA methyltransferase is an independent predictor of shortened progression free survival in patients with low-grade diffuse astrocytomas. Brain Pathol 13:176–184
Acknowledgments
We are indebted to the Research and Development Unit of Azienda Ospedaliera di Padova for the research funding.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Tosoni, A., Franceschi, E., Ermani, M. et al. Temozolomide three weeks on and one week off as first line therapy for patients with recurrent or progressive low grade gliomas. J Neurooncol 89, 179–185 (2008). https://doi.org/10.1007/s11060-008-9600-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11060-008-9600-y