Background/Aim: The current meta-analysis evaluated the survival outcomes of newly diagnosed glioblastoma patients treated with radiotherapy (RT) alone and with RT + temozolomide (TMZ). Methods: Relevant studies were identified by an extensive literature search in Medline, Current Contents and Cochrane databases by 2 independent reviewers using the terms “glioblastoma multiforme/glioblastoma, TMZ, radiation therapy/RT and survival.” Results: Results revealed a median survival of 13.41-19 months in the combined treatment group, as opposed to 7.7-17.1 months in the RT-alone group. Progression-free survival (PFS) was also significantly different between the 2 groups (RT + TMZ, 6.3-13 months; RT-alone, 5-7.6 months). While there was no significant difference in the 6-month survival and 6-month PFS rates between the RT + TMZ and RT groups (pooled OR 0.690; p = 0.057 and OR 0.429, p = 0.052, respectively), the 1-year survival and 1-year PFS rates showed significant difference (OR 0.469; p = 0.030 and OR 0.245, p < 0.001, respectively). Conclusions: Concomitant RT + TMZ is more effective and improves the overall survival and PFS in patients with newly diagnosed glioblastoma.

1.
Ostrom QT, Gittleman H, Liao P, et al: CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2007-2011. Neuro Oncol 2014;16(suppl 4):iv1-iv63.
2.
Adamson C, Kanu OO, Mehta AI, et al: Glioblastoma multiforme: a review of where we have been and where we are going. Expert Opin Investig Drugs 2009;18:1061-1083.
3.
Zhang X, Zhang W, Cao WD, Cheng G, Zhang YQ: Glioblastoma multiforme: molecular characterization and current treatment strategy (review). Exp Ther Med 2012;3:9-14.
4.
Ohgaki H, Dessen P, Jourde B, et al: Genetic pathways to glioblastoma: a population-based study. Cancer Res 2004;64:6892-6899.
5.
Capocaccia R, Gatta G, Roazzi P, et al: The EUROCARE-3 database: methodology of data collection, standardisation, quality control and statistical analysis. Ann Oncol 2003;14(suppl 5):v14-v27.
6.
Nagasawa DT, Chow F, Yew A, Kim W, Cremer N, Yang I: Temozolomide and other potential agents for the treatment of glioblastoma multiforme. Neurosurg Clin N Am 2012;23:307-322, ix.
7.
Hottinger AF, Stupp R, Homicsko K: Standards of care and novel approaches in the management of glioblastoma multiforme. Chin J Cancer 2014;33:32-39.
8.
Chang CH, Horton J, Schoenfeld D, et al: Comparison of postoperative radiotherapy and combined postoperative radiotherapy and chemotherapy in the multidisciplinary management of malignant gliomas. A joint Radiation Therapy Oncology Group and Eastern Cooperative Oncology Group study. Cancer 1983;52:997-1007.
9.
Solero CL, Monfardini S, Brambilla C, et al: Controlled study with BCNU vs. CCNU as adjuvant chemotherapy following surgery plus radiotherapy for glioblastoma multiforme. Cancer Clin Trials 1979;2:43-48.
10.
Thomas RP, Recht L, Nagpal S: Advances in the management of glioblastoma: the role of temozolomide and MGMT testing. Clin Pharmacol 2013;5:1-9.
11.
Newlands ES, Stevens MF, Wedge SR, Wheelhouse RT, Brock C: Temozolomide: a review of its discovery, chemical properties, pre-clinical development and clinical trials. Cancer Treat Rev 1997;23:35-61.
12.
Koukourakis GV, Kouloulias V, Zacharias G, et al: Temozolomide with radiation therapy in high grade brain gliomas: pharmaceuticals considerations and efficacy; a review article. Molecules 2009;14:1561-1577.
13.
Hirose Y, Berger MS, Pieper RO: p53 effects both the duration of G2/M arrest and the fate of temozolomide-treated human glioblastoma cells. Cancer Res 2001;61:1957-1963.
14.
Stupp R, Mason WP, van den Bent MJ, et al: Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 2005;352:987-996.
15.
Szczepanek D, Marchel A, Moskała M, Krupa M, Kunert P, Trojanowski T: Efficacy of concomitant and adjuvant temozolomide in glioblastoma treatment. A multicentre randomized study. Neurol Neurochir Pol 2013;47:101-108.
16.
Athanassiou H, Synodinou M, Maragoudakis E, et al: Randomized phase II study of temozolomide and radiotherapy compared with radiotherapy alone in newly diagnosed glioblastoma multiforme. J Clin Oncol 2005;23:2372-2377.
17.
Gerstein J, Franz K, Steinbach JP, Seifert V, Rödel C, Weiss C: Radiochemotherapy with temozolomide for patients with glioblastoma. Prognostic factors and long-term outcome of unselected patients from a single institution. Strahlenther Onkol 2011;187:722-728.
18.
Stupp R, Hegi ME, Mason WP, et al: Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol 2009;10:459-466.
19.
Kanu OO, Mehta A, Di C, et al: Glioblastoma multiforme: a review of therapeutic targets. Expert Opin Ther Targets 2009;13:701-718.
20.
Brada M, Stenning S, Gabe R, et al: Temozolomide versus procarbazine, lomustine, and vincristine in recurrent high-grade glioma. J Clin Oncol 2010;28:4601-4608.
21.
Brandes AA, Bartolotti M: Neuro-oncology: treatment decisions in elderly patients with glioblastoma. Nat Rev Neurol 2012;8:664-665.
22.
Liberati A, Altman DG, Tetzlaff J, et al: The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. Ann Intern Med 2009;151:W65-W94.
23.
Higgins J: Cochrane Handbook for Systematic Reviews of Interventions, Version 5.1.0, updated March 2011. Chichester, West Sussex, UK, The Cochrane Collaboration, 2011.
24.
Sutton AJ, Duval SJ, Tweedie RL, Abrams KR, Jones DR: Empirical assessment of effect of publication bias on meta-analyses. BMJ 2000;320:1574-1577.
25.
Kocher M, Frommolt P, Borberg SK, et al: Randomized study of postoperative radiotherapy and simultaneous temozolomide without adjuvant chemotherapy for glioblastoma. Strahlenther Onkol 2008;184:572-579.
26.
Karacetin D, Okten B, Yalcin B, Incekara O: Concomitant temozolomide and radiotherapy versus radiotherapy alone for treatment of newly diagnosed glioblastoma multiforme. J BUON 2011;16:133-137.
27.
Chakravarti A, Erkkinen MG, Nestler U, et al: Temozolomide-mediated radiation enhancement in glioblastoma: a report on underlying mechanisms. Clin Cancer Res 2006;12:4738-4746.
28.
Watanabe R, Nakasu Y, Tashiro H, et al: O6-methylguanine DNA methyltransferase expression in tumor cells predicts outcome of radiotherapy plus concomitant and adjuvant temozolomide therapy in patients with primary glioblastoma. Brain Tumor Pathol 2011;28:127-135.
29.
Yin AA, Cheng JX, Zhang X, Liu BL: The treatment of glioblastomas: a systematic update on clinical Phase III trials. Crit Rev Oncol Hematol 2013;87:265-282.
30.
Hart MG, Garside R, Rogers G, Stein K, Grant R: Temozolomide for high grade glioma. Cochrane Database Syst Rev 2013;4:CD007415.
31.
Yin AA, Zhang LH, Cheng JX, et al: Radiotherapy plus concurrent or sequential temozolomide for glioblastoma in the elderly: a meta-analysis. PLoS One 2013;8:e74242.
32.
Yin AA, Cai S, Dong Y, et al: A meta-analysis of temozolomide versus radiotherapy in elderly glioblastoma patients. J Neurooncol 2014;116:315-324.
33.
Zarnett OJ, Sahgal A, Gosio J, et al: Treatment of elderly patients with glioblastoma: a systematic evidence-based analysis. JAMA Neurol 2015;72:589-596.
34.
Malmström A, Grønberg BH, Marosi C, et al: Temozolomide versus standard 6-week radiotherapy versus hypofractionated radiotherapy in patients older than 60 years with glioblastoma: the Nordic randomised, phase 3 trial. Lancet Oncol 2012;13:916-926.
35.
Wick W, Platten M, Meisner C, et al: Temozolomide chemotherapy alone versus radiotherapy alone for malignant astrocytoma in the elderly: the NOA-08 randomised, phase 3 trial. Lancet Oncol 2012;13:707-715.
36.
Metcalfe E, Karaoglanoglu O, Akyazici E: Radiotherapy with or without temozolomide in elderly patients aged ≥ 70 years with glioblastoma. Contemp Oncol (Pozn) 2016;20:251-255.
37.
Perry JR, O'Callaghan CJ, et al: A Phase III Randomized Controlled Trial of Short-Course Radiotherapy with or without Concomitant and Adjuvant Temozolomide in Elderly Patients with Glioblastoma (CCTG CE.6, EORTC 26062-22061, TROG 08.02, NCT00482677), 2016.
38.
McNamara MG, Sahebjam S, Mason WP: Emerging biomarkers in glioblastoma. Cancers (Basel) 2013;5:1103-1119.
39.
Sun H, Du S, Liao G, Xie X, Ren C, Yuan YW: Do glioma patients derive any therapeutic benefit from taking a higher cumulative dose of temozolomide regimens?: a meta-analysis. Medicine (Baltimore) 2015;94:e827.
40.
Balducci M, Diletto B, Chiesa S, et al: Low-dose fractionated radiotherapy and concomitant chemotherapy for recurrent or progressive glioblastoma: final report of a pilot study. Strahlenther Onkol 2014;190:370-376.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.