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Table 1

Myrna R. Rosenfeld, MD, PhD, Karen Albright, CRNP, and Amy A. Pruitt, MD

University of Pennsylvania School of Medicine, Philadelphia, PA

Manuscript received December 1, 2010; accepted April 15, 2011.

Correspondence to: Myrna R. Rosenfeld, MD, PhD, Department of Neurology, 3 W. Gates, University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104; telephone: 215-746-2820; fax: 215-746-2818; e-mail: myrna.rosenfeld@uphs.upenn.edu.

Despite treatment, glioblastoma (GB) inevitably recurs, and there is often no clear standard of care to follow. This article reviews the treatment options for recurrent GB and anaplastic gliomas. The three FDA-approved treatments for recurrent GB are biodegradable carmustine-impregnated wafers; bevacizumab; and the NovoTTF-100A System, which delivers low-intensity, alternating electrical fields to the tumor bed. Treatment decisions must take into consideration prior therapies, the extent and location of recurrence, and the patient’s general medical condition, as well as the rapidity of tumor growth, extent of edema, mass effect, need for steroids, and symptoms. New treatment strategies are emerging based on the identification of prognostic and predictive markers and defining distinct molecular subtypes of GB.

Glioblastoma (grade IV glioma, GB) is the most common of the primary malignant gliomas. Advances in the past decade have clarified that adjuvant treatment can improve quality of life and survival. The current standard of care for newly diagnosed patients with GB after optimal resection is focal radiation with concurrent (chemoradiation) and post-radiation temozolomide (Temodar). This regimen was shown to improve overall survival in a randomized phase III study.1 Furthermore, a subgroup of patients whose tumors were shown to have low levels of O6-methylguanine DNA methyltransferase (MGMT), the enzyme that repairs DNA damage due to temozolomide, showed overall survival of 46% at 2 years and 14% at 5 years.2,3

Biodegradable wafers impregnated with carmustine (Gliadel) implanted at the time of resection are another approved therapy for patients with newly diagnosed high-grade gliomas (GB and anaplastic gliomas, grade III glioma).4 Although short-term survivals for GB patients are similar with Gliadel compared to focal radiation with concurrent and post-radiation temozolomide, the latter results in superior long-term survival (1.9% at 56 months for Gliadel and 9.8% at 60 months for temozolomide).3,5 The nitrosoureas lomustine (CeeNU) and carmustine (BiCNU) were approved in the 1970s for use as single agents or in combination therapy in patients with glioma who had received surgery and/or radiation. These agents no longer have a clear role in the initial treatment of malignant glioma, although practitioners use them, often in combination therapy, for patients with recurrent GB and anaplastic oligodendrogliomas, a ¬chemosensitive subtype of glioma.6