Establishing the standard of care for patients with newly diagnosed and recurrent glioblastoma.
The current standard of care for patients with newly diagnosed glioblastoma includes maximal safe tumor resection followed by concurrent external-beam radiation with daily low-dose temozolomide followed by 6 to 12 months of adjuvant temozolomide, typically by using a cycle of 5 consecutive days out of 28. Efforts to improve on these results from the European Organisation for Research and Treatment of Cancer (EORTC)/National Cancer Institute of Canada (NCIC) trial using either dose-dense chemotherapy strategies or combinations with signal transduction modulators have, to date, been unsuccessful. Two large international randomized trials examining the efficacy of adding bevacizumab, an antiangiogenic agent, to the standard treatment have been completed, with expectations of results within in the next 2 years. For recurrent glioblastoma, there are no firmly established standards of care. Although intracavitary insertion of carmustine-impregnated polymers has been approved by the U.S. Food and Drug Administration (FDA), this strategy is not widely used. Bevacizumab has been FDA approved for recurrent glioblastoma, but no randomized trial has clearly demonstrated a survival benefit. Alternative dosing schedules of temozolomide (i.e., metronomic) has modest activity even in patients with prior temozolomide exposure. Clinical trials testing small-molecule signal transduction modulators have been disappointing, although most report a small response rate, suggesting that molecularly definable tumor subpopulations may help guide treatment decisions. Successful implementation of marker-based treatment would lead to personalized care and the creation of individualized standards of care.
From the Department of Neuro-oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX.
Mark R
MR
Gilbert