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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

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.

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