According to results recently published in the New England Journal of Medicine, the addition of the chemotherapy agent Temodar® (temozolomide) to radiation therapy improves survival in patients with glioblastoma multiforme; however, only approximately half of the patients who receive Temodar® derive a great benefit from the agent. There is now a DNA test that can help predict which patients with glioblastoma multiforme are more likely to derive a major benefit from the addition of Temodar® to radiation and which patients are less likely to achieve a major benefit from treatment with the addition of Temodar® to radiation therapy, compared to radiation therapy alone. Patients who are less likely to benefit from treatment with Temodar® may wish to pursue alternative treatment options.
Approximately 20,000 people are diagnosed with primary brain cancer in the United States each year. Primary brain cancer is cancer that originates in the brain and has not spread from cancer already located elsewhere in the body. Glioblastoma is one of the most common, and fatal, types of primary brain cancer. When glioblastoma is present, glial cells become malignant and grow out of control. Glial cells are the most abundant cells present in the nervous system, providing many supportive functions that facilitate the majority of processes conducted by neurons (cells that transmit impulses between the brain, spinal column and nerves). Standard treatment options for glioblastoma consist of surgical removal of the cancer if possible, radiation therapy and/or chemotherapy. However, even with the most aggressive treatment available, most patients will survive less than one year after diagnosis. Because of the poor prognosis for patients with this disease, researchers are attempting to develop more effective treatment strategies to improve survival and/or improve quality of life of glioblastoma patients.
One obstacle in the treatment of brain cancer is the inability of the majority of chemotherapy agents to penetrate the blood-brain barrier. The blood-brain barrier is a membrane that surrounds the brain and spinal cord and protects the brain and nervous system by allowing only very select molecules to pass through. Temodar® is a chemotherapy agent that has the ability to penetrate the blood-brain barrier and provide anti-cancer effects in the brain. Results from previous clinical studies have indicated that Temodar® in addition to radiation therapy as initial treatment may provide improved survival for patients with glioblastoma multiforme.
Researchers affiliated with the European Organization for Research and Treatment of Cancer (EORTC) and the National Cancer Institute of Canada (NCIC) recently conducted a clinical trial to directly compare the combination of Temodar® and radiation therapy to radiation therapy alone in patients with glioblastoma multiforme. This trial included 573 patients with newly diagnosed, stage IV glioblastoma multiforme. Forty percent of the patients had their cancer completely removed surgically, 44% had their cancer partially removed surgically, and 16% only had a biopsy (tissue sample removed). Patients were divided into two groups: one group was treated with radiation therapy only and one group was treated with the same radiation therapy plus treatment with Temodar® during radiation therapy, followed by an additional 6 cycles of treatment with Temodar®. Overall, patients who received Temodar®/radiation had an improved survival over those treated with radiation therapy alone. The average overall survival was approximately 14.6 months for those treated with Temodar®/radiation, compared to 12.1 months for those treated with radiation alone. The average progression-free survival was nearly 7 months for patients treated with Temodar®/radiation, compared to 5.0 months for those treated with radiation therapy alone. At 2 years, overall survival was 26.5% in the group of patients treated with Temodar®/radiation, compared to 10.4% for those treated with radiation therapy alone. Progression-free survival was 10.7% for those treated with Temodar®/radiation, compared to 1.5% for those treated with radiation alone.
The researchers from this trial also performed DNA testing on 245 of the 575 cancer samples. They tested the for a molecular structure referred to as methylation within an area of the gene referred to as MGMT. Overall, patients with a “methylated” MGMT derived great benefit from the addition of Temodar® to radiation in terms of the average duration of survival as well as survival at 2 years. Conversely, patients with an “unmethylated” MGMT did not derive the major benefit from the addition of Temodar® to radiation therapy as those with methylated MGMT.
The researchers concluded that patients with newly diagnosed glioblastoma multiforme derive survival benefit from the addition of Temodar® to radiation therapy compared to radiation therapy alone. However, it appears that patients with a methylated promoter region of MGMT derive a greater benefit from Temodar® than those with an unmethylated region of MGMT. Patients with glioblastoma multiforme may wish to speak with their physician about their individual risks and benefits of treatment with Temodar®, as well as DNA testing for methylation of MGMT.
 Stupp R, Mason WP, van den Bent MJ, Weller M, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. New England Journal of Medicine. 2005;352:987-996.
 Hegi ME, Diserens A-C, Gorlia T, et al. MGMT gene silencing and benefit from temozolomide in glioblastoma. New England Journal of Medicine. 2005;352:997-1003.
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