The Role of Chemotherapy in the Treatment of Low-grade Gliomas
Authors:
R. Lakomý 1; T. Kazda 2,3; A. Poprach 1; P. Pospíšil 2; R. Jančálek 4; P. Šlampa 2
Authors‘ workplace:
Klinika komplexní onkologické péče LF MU a Masarykův onkologický ústav, Brno
1; Klinika radiační onkologie LF MU a Masarykův onkologický ústav, Brno
2; CEITEC – Středoevropský technologický institut, MU, Brno
3; Neurochirurgická klinika LF MU a FN U sv. Anny v Brně
4
Published in:
Klin Onkol 2017; 30(5): 343-348
Category:
Review
doi:
https://doi.org/10.14735/amko2017343
Overview
Background:
The standard postsurgical options for low-grade gliomas include watchful waiting or radiotherapy depending on the risk factors for recurrence. The use of chemotherapy for the treatment of this disease is generally controversial, although the recently published results of the first of two large randomized phase III clinical trials (RTOG 9802 a EORTC 22033-26033), focusing on the evaluation of chemotherapy for the upfront treatment of newly diagnosed low-grade gliomas, are reassuring in this respect. The long-term results of a RTOG 9802 comparing radiotherapy alone with radiotherapy and six cycles of adjuvant PCV chemotherapy (procarbazine, lomustine, vincristine) in patients with high-risk low-grade gliomas will probably have an impact on daily clinical practice. The increase in median overall survival from 7.8 years to 13.3 years, mainly for patients with oligodendrogliomas, is unprecedented, but the toxicity of PCV is too high and molecular marker analysis remains inadequate. It is still unclear whether less toxic temozolomide can replace PCV and whether temozolomide can be used upfront alone instead of with radiotherapy. This question is addressed by the ongoing EORTC 22033-26033 study. The preliminary results show no significant difference in progression-free survival between patients receiving radiotherapy and those receiving temozolomide alone. Treatment with temozolomide was not associated with an improvement in cognitive function compared with treatment with radiotherapy. Despite limited follow-up, the study clearly confirmed the importance of molecular characterization of low-grade gliomas, as currently defined in the new 2016 WHO Classification of Tumors of the Central Nervous System.
Aim:
The aim of the review is to summarize available information from listed key clinical trials of chemotherapy for low-grade gliomas and draw attention to unresolved issues concerning the use of chemotherapy for the treatment of this disease.
Key words:
glioma – astrocytoma – chemotherapy – PCV – temozolomide – RTOG 9802
This work was supported by MH CZ – RVO (MMCI, 00209805) and by project of the Ministry of Education, Youths and Sports of the Czech Republic CEITEC 2020 (LQ1601).
The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.
The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.
Submitted:
21. 2. 2017
Accepted:
20. 3. 2017
Sources
1. van den Bent MJ. Chemotherapy for low-grade glioma: when, for whom, which regimen? Curr Opin Neurol 2015; 28 (6): 633–938. doi: 10.1097/WCO.0000000000000257.
2. Polívka J Jr, Polívka J, Rohan V et al. Aktuální pohled na management nízkostupňových gliových nádorů centrálního nervového systému. Cesk Slov Neurol N 2016; 79/112 (5): 534–540. doi: 10.14735/amcsnn2016534.
3. Duffau H, Taillandier L. New concepts in the management of diffuse low-grade glioma: proposal of a multistage and individualized therapeutic approach. Neuro Oncol 2015; 17 (3): 332–342. doi: 10.1093/neuonc/nou153.
4. Youland RS, Schomas DA, Brown PD el al. Changes in presentation, treatment, and outcomes of adult low-grade gliomas over the past fifty years. Neuro Oncol 2013; 15 (8): 1102–1110. doi: 10.1093/neuonc/not 080.
5. Douw L, Klein M, Fagel SS et al. Cognitive and radiological effects of radiotherapy in patients with low-grade glioma: long-term follow-up. Lancet Neurol 2009; 8 (9): 810–818. doi: 10.1016/S1474-4422 (09) 70204-2.
6. Pignatti F, van den Bent M, Curran D et al. Prognostic factors for survival in adult patients with cerebral low-grade glioma. J Clin Oncol 2002; 20 (8): 2076–2084.
7. Buckner JC, Shaw EG, Pugh SL et al. Radiation plus procarbazine, CCNU, and vincristine in low-grade glioma. N Engl J Med 2016; 374 (14): 1344–1355. doi: 10.1056/ NEJMoa1500925.
8. Baumert BG, Hegi ME, van den Bent MJ et al. Temozolomide chemotherapy versus radiotherapy in high-risk low-grade glioma (EORTC 22033-26033): a randomised, open-label, phase 3 intergroup study. Lancet Oncol 2016; 17 (11): 1521–1532. doi: 10.1016/S1470-2045 (16) 30313-8.
9. Reijneveld JC, Taphoorn MJ, Coens C et al. Health-related quality of life in patients with high-risk low-grade glioma (EORTC 22033-26033): a randomised, open-label, phase 3 intergroup study. Lancet Oncol 2016; 17 (11): 1533–1542. doi: 10.1016/S1470-2045 (16) 30305-9.
10. van den Bent MJ. Practice changing mature results of RTOG study 9802: another positive PCV trial makes adjuvantchemotherapy part of standard of care in low-grade glioma. Neuro Oncol 2014; 16 (12): 1570–1574. doi: 10.1093/neuonc/nou297.
11. Ziu M, Olson JJ. Update on the evidence-based clinical practice parameter guidelines for the treatment of adults with diffuse low grade glioma: the role of initial chemotherapy. J Neurooncol 2016; 128 (3): 487–489. doi: 10.1007/s11060-016-2137-6.
12. Louis DN, Perry A, Reifenberger G et al. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol 2016; 131 (6): 803–820. doi: 10.1007/s00401-016-1545-1.
13. Mandonnet E, Wager M, Almairac F et al. Survey on current practice within the European Low-Grade Glioma Network: where do we stand and what is the next step? Neurooncol Pract. In press 2017. doi: 10.1093/nop/npw031.
14. Cairncross G, Wang M, Shaw E et al. Phase III trial of chemoradiotherapy for anaplastic oligodendroglioma: long-term results of RTOG 9402. J Clin Oncol 2013; 31 (3): 337–343. doi: 10.1200/JCO.2012.43.2674.
15. van den Bent MJ, Brandes AA, Taphoorn MJ et al. Adjuvant procarbazine, lomustine, and vincristine chemotherapy in newly diagnosed anaplastic oligodendroglioma: long-term follow-up of EORTC Brain Tumor Group study 26951. J Clin Oncol 2013; 31 (3): 344–350. doi: 10.1200/JCO.2012.43.2229.
16. van den Bent MJ. Results of the interim analysis of the EORTC randomized phase III CATNON trial on concurrent and adjuvant temozolomide in anaplastic glioma without 1p/19q co-deletion: An Intergroup trial. 2016 ASCO Annual Meeting. J Clin Oncol 2016; 34 (Suppl): abstr. LBA2000.
17. Stupp R, Mason WP, van den Bent MJ et al. Radiotherapy plus concomitant and adjuvant Temozolomide for Glioblastoma. N Engl J Med 2005; 352 (10): 987–996.
18. Lhotská H, Zemanová Z, Kramář F et al. Molecular cytogenetic analysis of chromosomal aberrations in cells of low grade gliomas and its contribution for tumour classification. Klin Onkol 2014; 27 (3): 183–191. doi: 10.14735/amko2014183.
19. Reifenberger G, Wirsching HG, Knobbe-Thomsen CB et al. Advances in the molecular genetics of gliomas – implications for classification and therapy. Nat Rev Clin Oncol 2016. doi: 10.1038/nrclinonc.2016.204.
20. Jenkins RB, Blair H, Ballman KV et al. A t (1; 19) (q10; p10) mediates the combined deletions of 1p and 19q and predicts a better prognosis of patients with oligodendroglioma. Cancer Res 2006; 66 (20): 9852–9861.
21. Polivka J Jr, Polivka J, Repik T et al. Co-deletion of 1p/19q as Prognostic and Predictive Biomarker for Patients in West Bohemia with Anaplastic Oligodendroglioma. Anticancer Res 2016; 36 (1): 471–476.
22. Kramář F, Minárik M, Belšánová B et al. Genetické a epigenetické faktory podmiňující vznik a prognózu mozkových gliomů – souhrn současných poznatků. Cesk Slov Neurol N 2016; 79/112 (4): 400–405.
23. Suzuki H, Aoki K, Chiba K et al. Mutational landscape and clonal architecture in grade II and III gliomas. Nat Genet 2015; 47 (5): 458–468. doi: 10.1038/ng.3273.
24. Yan H, Parsons DW, Jin G et al. IDH1 and IDH2 mutations in gliomas. N Engl J Med 2009; 360 (8): 765–773. doi: 10.1056/NEJMoa0808710.
25. van den Bent MJ, Erdem Eraslan L, Idbaih A et al. MGMT-STP27 methylation status as predictive marker for response to PCV in anaplastic oligodendrogliomas and oligoastrocytomas. A report from EORTC study 26951. Clin Cancer Res 2013; 19 (19): 5513–5522. doi: 10.1158/1078-0432.CCR-13-1157.
26. Wick W, Meisner C, Hentschel B et al. Prognostic or predictive value of MGMT promoter methylation in gliomas depends on IDH1 mutation. Neurology 2013; 81 (17): 1515–1522. doi: 10.1212/WNL.0b013e3182a95680.
27. Laack NN, Sarkaria JN, Buckner JC. Radiation Therapy Oncology Group 9802: Controversy or Consensus in the Treatment of Newly Diagnosed Low-Grade Glioma? Semin Radiat Oncol 2015; 25 (3): 197–202. doi: 10.1016/ j.semradonc.2015.02.004.
28. Kazda T, Lakomy R, Pospisil P. Kontroverze v pooperační léčbě low-grade gliomů. Klin Onkol 2017; 30 (5): 337–342. doi: 10.14735/amko2017337.
Labels
Paediatric clinical oncology Surgery Clinical oncologyArticle was published in
Clinical Oncology
2017 Issue 5
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