Originally published as JCO Early Release 10.1200/JCO.2008.21.6895 on July 27 2009

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Talampanel With Standard Radiation and Temozolomide in Patients With Newly Diagnosed Glioblastoma: A Multicenter Phase II Trial

From the New Approaches to Brain Tumor Therapy CNS Consortium, Baltimore, MD.

Corresponding author: Stuart A. Grossman, MD, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Cancer Research Building II – Suite 1M-16, 1550 Orleans St, Baltimore, MD 21231; e-mail: grossman{at}jhmi.edu.

Purpose Recent data suggest that the glutamatergic system is important in the proliferation and migration of glioblastoma. Talampanel is a well-tolerated, oral -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor blocker that could be beneficial in this disease.

Patients and Methods This trial was designed to estimate overall survival in adults with newly diagnosed glioblastoma treated with talampanel in addition to standard radiation (RT) and temozolomide (TMZ). A secondary purpose was to evaluate talampanel toxicity in this setting. Talampanel was initiated with RT + TMZ and discontinued for toxicity or disease progression. Survival was compared with historical controls.

Results Seventy-two patients were enrolled from December 2005 to July 2006. Their median age was 60 years (range, 37 to 85 years, with 17% > 70 years), median Karnofsky performance score was 90 (range, 70 to 100), and 77% had a debulking procedure. With a median follow-up time of 18 months, 55 patients (76%) have died, yielding a median survival time of 18.3 months (95% CI, 14.6 to 22.5 months). When the 60 patients who were 18 to 70 years old were compared with the European Organisation for Research and Treatment of Cancer (EORTC) RT + TMZ data, the median survival (20.3 v 14.6 months, respectively) and percentage of patients surviving at 24 months (41.7% v 26.5%, respectively; P = .02) seemed superior. The percentage of patients methylated at O⁶-methylguanine–DNA methyltransferase was lower than on the EORTC study (29% v 43%, respectively). Talampanel was well tolerated and did not increase the known hematologic or nonhematologic toxicities of TMZ.

Conclusion Talampanel can be added to RT + TMZ without significant additional toxicity. The encouraging survival results in methylated and unmethylated patients suggest that blocking AMPA receptors may be a useful strategy in newly diagnosed glioblastoma.

Written on behalf of the New Approaches to Brain Tumor Therapy CNS Consortium.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Clinical Trials repository link available on JCO.org.

Clinical trial information can be found for the following: NCT00567592.

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