Glioblastoma multiforme: a review of where we have been and where we are
going. Adamson C, Kanu OO, Mehta AI, Di C, Lin N, Mattox AK, Bigner DD.
Expert Opin Investig Drugs. 2009 Aug;18(8):1061-83.
Duke Medical Center, MSRB 1 Box 2624, Durham, NC 27712,
USA. cory.adamson@duke.edu
Malignant gliomas such as glioblastoma multiforme (GBM)
present some of the greatest challenges in the management of cancer patients
worldwide, despite notable recent achievements in oncology. Even with
aggressive surgical resections using state-of-the-art preoperative and
intraoperative neuroimaging, along with recent advances in radiotherapy and
chemotherapy, the prognosis for GBM patients remains dismal: median survival
after diagnosis is about 14 months. Established good prognostic factors are
limited, but include young age, high Karnofsky Performance Status (KPS), high
mini-mental status examination score, O6-methylguanine methyltransferase
promoter methylation, and resection of > 98% of the tumor. Standard treatment
includes resection, followed by concurrent chemotherapy and radiotherapy. GBM
research is being conducted worldwide at a remarkable pace, with some of the
more recent promising studies focused on identification of aberrant genetic
events and signaling pathways, tumor stem cell identification and
characterization, modulation of tumor immunological responses, combination
therapies, and understanding of the rare long-term survivors. Past treatment
strategies have failed for various reasons; however, newer strategies in
trials today and on the horizon encourage optimism. To help illustrate 'where
we have been' with this fatal disease and 'where we are going' with
contemporary studies, we include in this review a detailed history of Phase
III clinical trials for GBM, with a final emphasis on exciting new treatment
strategies that offer hope for future GBM therapy.