Meeting Abstract

Current status of malignant glioma chemotherapy - hype or hope?

R. Stupp

University Hospital CHUV, Multidisciplinary Oncology Center, Lausanne, Switzerland

Brain tumors are among the most debilitating diseases. 
Treatment options are limited to surgery and radiation, the role of chemotherapy has been marginal. 
Nitrosourea-based chemotherapy has shown activity in selected patients, but failed to show a benefit as adjuvant therapy for malignant glioma in a large randomized trial. 
Higher response rates to PCV-chemotherapy have been demonstrated for oligodendroglioma, in particular when associated with deletions on chromosomes 1p and 19q. 
Recently temozolomide (TMZ), a novel alkylating agent has been approved. 
The low response rates of only 5-8% in glioblastoma (higher in anaplastic astrocytoma) and the absence of phase III data have cast doubts whether TMZ offers a clinically relevant benefit over older alkylating agents. 
Some benefit may simply be derived by the closer follow-up and better supportive care in patients receiving chemotherapy. 
More intensive TMZ schedules are being explored. 
Continuous administration of alkylating agents will deplete the cells of the DNA repair enzyme O6-alkyltransferase (AGT), and may thus have a theoretical advantage over the intermittent schedules. 
No comparative data are available. 
Combining X-irradiation with TMZ has been shown to be at least additive in vitro in some glioblastoma cell lines. 
Using chemotherapy with intrinsic activity immediately after diagnosis together with radiotherapy may allow eliminating microscopic infiltrating disease early in the disease course. 
Concomitant administration of chemoradiotherapy may increase the radiosensitivity. 
In a phase II trial we treated 64 patients with newly diagnosed glioblastoma multiforme with TMZ and concomitant radiotherapy. 
At a median follow-up of now over 3 years the median survival of 14.3 mo (95% c.i. 10.4-18.3) and in particular the 2-year survival of 28% (17-39%) are promising for this poor-prognosis group of patients. 
A large international randomized trial conducted by the EORTC and the NCI Canada has accrued over 550 patients. 
Conclusive results are expected in early 2004. 
Insights into gene expression and signaling pathways have allowed identifying new and specific treatment targets for malignant glioma. 
Trials using new agents blocking EGFR, PDGF and integrins are underway and some encouraging responses have been observed. 
The challenge remains to identify the patients who are most likely to benefit from new treatment approaches and integration of the novel agents into the existing multimodality treatments.

© 2003 Elsevier Ltd. All rights reserved.