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Glioblastoma—more questions than answers?

Nature Clinical Practice Oncology volume 3, pages 60–61 (2006)Cite this article

GLIOBLASTOMA MULTIFORME (GBM) is the most common primary tumor that occurs in the central nervous system in adults. This devastating neoplasm is characterized by progressive and profound physical and cognitive disability that ultimately culminates in death within 1–2 years of diagnosis in nearly all cases. Despite decades of intensive research, improvement in outcome has been elusive. In a recent population-based study, overall survival was 42%, 18% and 3% at 6, 12 and 24 months after diagnosis, respectively, despite access to state-of-the-art medical care.1 Surgery and radiotherapy (XRT), traditional cornerstones of therapy, provide palliative benefit, while the value of chemotherapy has been limited.2 Fortunately, the therapeutic options for GBM patients are increasing. Nonetheless, further progress hinges on overcoming long-standing hurdles, including tumoral heterogeneity, impaired drug delivery and therapy resistance, as well as resolving critical questions arising from recent therapeutic advances.

Temozolomide (TMZ), a DNA methylator, was approved in March 2005 for newly diagnosed GBM patients, based on a survival advantage demonstrated in a multinational, randomized phase III study.3 In this study, GBM patients randomized to receive TMZ (75 mg/m2/day) concurrently during XRT (75 mg/m2/day), followed by six cycles of adjuvant TMZ (150–200 mg/m2/day for 5 days every 28 days), had superior progression-free survival and overall survival (OS) compared with patients treated with XRT alone. Specifically, the median progression-free survival and OS values for these patients treated with TMZ/XRT+TMZ were 6.9 and 14.6 months, respectively, compared with 5.0 and 12.1 months for those treated with XRT alone. Of note, the OS benefit increased with time following treatment; the 24-month survival rate was 26.5% for the TMZ/XRT+TMZ group compared with 10.4% for the XRT group. Importantly, the benefit associated with TMZ was statistically significant across all patient subsets, with the exception of patients with poor performance status, in whom a trend toward statistical significance was noted. In addition, TMZ/XRT+TMZ was well tolerated, with grade ≥3 hematological toxicity observed in approximately 10% of patients.

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Acknowledgements

This work was supported by NIH Grants NS20023 and CA11898, NIH Grant MO1 RR 30, GCRC Program, NCRR, NCI SPORE 1 P20 CA096890, and additional funding support from the Pediatric Brain Tumor Foundation of the United States and the Accelerate Brain Cancer Cure (ABC2) Foundation.

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  1. associate professor in the Departments of Surgery and Pediatrics, Duke University Medical Center, Durham, NC, USA

    David A Reardon

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  1. David A Reardon
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Correspondence to David A Reardon.

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Schering-Plough, consultant (< $5000/yr) Novartis Pharmaceuticals, consultant (< $5000/yr) Genentech, stock (< $5000).

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Reardon, D. Glioblastoma—more questions than answers?. Nat Rev Clin Oncol 3, 60–61 (2006). https://doi.org/10.1038/ncponc0423

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