This Article Full Text Full Text (PDF) eLetters: Submit a response to this article Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services E-mail this article link to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints/Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Stupp, R. Search for Related Content PubMed PubMed Citation Articles by Stupp, R.

Changing Paradigms—An Update on the Multidisciplinary Management of Malignant Glioma

^a Multidisciplinary Oncology Center, ^b Laboratory of Tumor Biology and Genetics at the Department of Neuro-surgery, and ^f Department of Radiation Oncology, University of Lausanne Hospitals, Lausanne, Switzerland; ^c Department of Neuro-Oncology, Erasmus University Hospital Rotterdam/Rotterdam Cancer Center, Rotterdam, The Netherlands; ^d Department of Medicine, Princess Margaret Hospital and the University of Toronto, Toronto, Ontario, Canada; ^e Department of Neurology, University of Tübingen, Tübingen, Germany; ^g Department of Clinical Neurosciences, University of Calgary and Foothills Hospital, Calgary, Alberta, Canada

Key Words. Malignant glioma • Radiotherapy • Chemotherapy • Temozolomide • MGMT

Correspondence: Roger Stupp, M.D., Multidisciplinary Oncology Center, University of Lausanne Hospitals, 46 Rue du Bugnon, Lausanne 1011, Switzerland. Telephone: 41-21-314-0156; Fax: 41-21-314-0737; e-mail: Roger.Stupp{at}chuv.ch

Treatment of malignant glioma requires a multidisciplinary team. Treatment includes surgery, radiotherapy, and chemotherapy. Recently developed agents have demonstrated activity against recurrent malignant glioma and efficacy if given concurrently with radiotherapy in the upfront setting. Oligodendroglioma with 1p/19q deletions has been recognized as a distinct pathologic entity with particular sensitivity to radiotherapy and chemotherapy. Randomized trials have shown that early neoadjuvant or adjuvant administration of procarbazine, lomustine, and vincristine chemotherapy prolongs disease-free survival; however, it has no impact on overall survival. Temozolomide, a novel alkylating agent, has shown modest activity against recurrent glioma. In combination with radiotherapy in newly diagnosed patients with glioblastoma, temozolomide significantly prolongs survival. Molecular studies have demonstrated that the benefit is mainly observed in patients whose tumors have a methylated methylguanine methyltransferase gene promoter and are thus unable to repair some of the chemotherapy-induced DNA damage. For lower-grade glioma, the use of chemotherapy remains limited to recurrent disease, and first-line administration is the subject of ongoing clinical trials. Irinotecan and agents like gefitinib, erlotinib, and imatinib targeting the epidermal growth factor receptor and platelet-derived growth factor receptor have shown some promise in recurrent malignant glioma. This review summarizes recent developments, focusing on the clinical management of patients in daily neuro-oncology practice.

This article has been cited by other articles:

				Y. Cao, J. D. Lathia, C. E. Eyler, Q. Wu, Z. Li, H. Wang, R. E. McLendon, A. B. Hjelmeland, and J. N. Rich Erythropoietin Receptor Signaling through STAT3 Is Required for Glioma Stem Cell Maintenance Genes & Cancer, January 1, 2010; 1(1): 50 - 61. [Abstract] [Full Text] [PDF]

				G. D. Maurer, I. Tritschler, B. Adams, G. Tabatabai, W. Wick, R. Stupp, and M. Weller Cilengitide modulates attachment and viability of human glioma cells, but not sensitivity to irradiation or temozolomide in vitro Neuro Oncology, December 1, 2009; 11(6): 747 - 756. [Abstract] [Full Text] [PDF]

				T. S. Armstrong, Y. Cao, M. E. Scheurer, E. Vera-Bolanos, R. Manning, M. F. Okcu, M. Bondy, R. Zhou, and M. R. Gilbert Risk analysis of severe myelotoxicity with temozolomide: The effects of clinical and genetic factors Neuro Oncology, December 1, 2009; 11(6): 825 - 832. [Abstract] [Full Text] [PDF]

				E. Razis, P. Selviaridis, S. Labropoulos, J. L. Norris, M.-J. Zhu, D. D. Song, T. Kalebic, M. Torrens, A. Kalogera-Fountzila, G. Karkavelas, et al. Phase II Study of Neoadjuvant Imatinib in Glioblastoma: Evaluation of Clinical and Molecular Effects of the Treatment Clin. Cancer Res., October 1, 2009; 15(19): 6258 - 6266. [Abstract] [Full Text] [PDF]

				G. Frosina DNA Repair and Resistance of Gliomas to Chemotherapy and Radiotherapy Mol. Cancer Res., July 1, 2009; 7(7): 989 - 999. [Abstract] [Full Text] [PDF]

				G. Karpel-Massler, U. Schmidt, A. Unterberg, and M.-E. Halatsch Therapeutic Inhibition of the Epidermal Growth Factor Receptor in High-Grade Gliomas: Where Do We Stand? Mol. Cancer Res., July 1, 2009; 7(7): 1000 - 1012. [Abstract] [Full Text] [PDF]

				J.-S. Guillamo, S. de Bouard, S. Valable, L. Marteau, P. Leuraud, Y. Marie, M.-F. Poupon, J.-J. Parienti, E. Raymond, and M. Peschanski Molecular Mechanisms Underlying Effects of Epidermal Growth Factor Receptor Inhibition on Invasion, Proliferation, and Angiogenesis in Experimental Glioma Clin. Cancer Res., June 1, 2009; 15(11): 3697 - 3704. [Abstract] [Full Text] [PDF]

				S. OSHIRO, H. TSUGU, F. KOMATSU, T. OHMURA, M. OHTA, S. SAKAMOTO, T. FUKUSHIMA, and T. INOUE Efficacy of Temozolomide Treatment in Patients with High-grade Glioma Anticancer Res, March 1, 2009; 29(3): 911 - 917. [Abstract] [Full Text] [PDF]

				W. Wick, M. Platten, and M. Weller New (alternative) temozolomide regimens for the treatment of glioma Neuro Oncology, February 1, 2009; 11(1): 69 - 79. [Abstract] [Full Text] [PDF]

				T. Yamauchi, M. Ogawa, and T. Ueda Carmustine-Resistant Cancer Cells Are Sensitized to Temozolomide As A Result of Enhanced Mismatch Repair during the Development of Carmustine Resistance Mol. Pharmacol., July 1, 2008; 74(1): 82 - 91. [Abstract] [Full Text] [PDF]

				I. Vlassenbroeck, S. Califice, A.-C. Diserens, E. Migliavacca, J. Straub, I. Di Stefano, F. Moreau, M.-F. Hamou, I. Renard, M. Delorenzi, et al. Validation of Real-Time Methylation-Specific PCR to Determine O6-Methylguanine-DNA Methyltransferase Gene Promoter Methylation in Glioma J. Mol. Diagn., July 1, 2008; 10(4): 332 - 337. [Abstract] [Full Text] [PDF]

				P. Pyrko, A. H. Schonthal, F. M. Hofman, T. C. Chen, and A. S. Lee The Unfolded Protein Response Regulator GRP78/BiP as a Novel Target for Increasing Chemosensitivity in Malignant Gliomas Cancer Res., October 15, 2007; 67(20): 9809 - 9816. [Abstract] [Full Text] [PDF]

				R. Stupp, M. E. Hegi, M. R. Gilbert, and A. Chakravarti Chemoradiotherapy in Malignant Glioma: Standard of Care and Future Directions J. Clin. Oncol., September 10, 2007; 25(26): 4127 - 4136. [Abstract] [Full Text] [PDF]

				T. Fukushima, T. Tezuka, T. Shimomura, S. Nakano, and H. Kataoka Silencing of Insulin-like Growth Factor-binding Protein-2 in Human Glioblastoma Cells Reduces Both Invasiveness and Expression of Progression-associated Gene CD24 J. Biol. Chem., June 22, 2007; 282(25): 18634 - 18644. [Abstract] [Full Text] [PDF]

				R. Stupp and M. E. Hegi Methylguanine Methyltransferase Testing in Glioblastoma: When and How? J. Clin. Oncol., April 20, 2007; 25(12): 1459 - 1460. [Full Text] [PDF]

				P. Hau, D. Koch, T. Hundsberger, E. Marg, B. Bauer, R. Rudolph, M. Rauch, A. Brenner, P. Rieckmann, J. Schuth, et al. Safety and feasibility of long-term temozolomide treatment in patients with high-grade glioma Neurology, February 27, 2007; 68(9): 688 - 690. [Abstract] [Full Text] [PDF]

				M. S. Bobola, S. Varadarajan, N. W. Smith, R. D. Goff, D. D. Kolstoe, A. Blank, B. Gold, and J. R. Silber Human Glioma Cell Sensitivity to the Sequence-Specific Alkylating Agent Methyl-Lexitropsin Clin. Cancer Res., January 15, 2007; 13(2): 612 - 620. [Abstract] [Full Text] [PDF]