Adding Temozolomide (Temodar®) to Radiation Increases Survival in Glioblastoma Multiforme
Keywords
Brain tumor, glioblastoma multiforme, malignant glioma, temozolomide (Temodar®), Temodar®. (Definitions of many terms related to cancer can be found in the Cancer.gov Dictionary.)
Summary
Updated results from a large randomized trial conducted in Europe and Canada have shown that the survival benefit obtained by adding the drug temozolomide (Temodar®) to postoperative radiation therapy in the treatment of a brain tumor called glioblastoma multiforme persisted through five years of follow-up.
Source
Lancet Oncology, March 9, 2009 (see the journal abstract).
Background
Glioblastoma multiforme, the most common and most aggressive form of brain cancer in adults, is considered incurable. Most patients die within a year of diagnosis. Promising early results with temozolomide led many physicians in the United States to treat glioblastoma patients with radiation followed by temozolomide even before clinical trials showed that this treatment was beneficial.
In 2000, the European Organization for the Treatment of Cancer and the National Cancer Institute of Canada began a randomized phase III trial to evaluate whether adding temozolomide to standard postoperative radiation therapy would improve the survival of patients with newly diagnosed glioblastoma. Initial findings from this trial, presented at the American Society of Clinical Oncology annual meeting in 2004, showed that temozolomide delayed disease progression and improved two-year survival. These results were published in the March 10, 2005, issue of the New England Journal of Medicine (see the journal abstract). The U.S. Food and Drug Administration approved temozolomide for treatment of glioblastoma on March 15, 2005.
However, these results did not answer the question of whether the survival benefit would last over time.
The Study
The trial included 573 patients who were randomly divided into two groups. Both groups received radiation therapy following biopsy or surgery. Patients in one group received temozolomide daily during the time that they were receiving radiation treatment and then for six monthly cycles after radiation therapy ended. Patients in the control group did not receive temozolomide.
Roger Stupp, M.D., of University Hospital in Lausanne, Switzerland, led the trial. (See the protocol summary.)
Results
Median survival in the radiation-plus-temozolomide group was 14.6 months, compared with 12.1 months in the radiation-only group. After two years, 26.5 percent of patients in the radiation-plus-temozolomide group were alive, compared with 10.4 percent of those who received radiation only. After 5 years, 9.8 percent of patients in the radiation-plus-temozolomide group and 1.9 percent of those in the radiation-only group were still alive.
The side effects of the combined therapy were mostly mild to moderate. Fewer than 10 percent of patients experienced a severe drop in blood cell counts, and only three developed severe infections.
Limitations
This trial enrolled only individuals who were under 70 years of age and who were in good overall health, noted Michael Prados, M.D., of the University of California, San Francisco, who commented on the presentation at ASCO. This suggests, he said, that the results might not be applicable to all patients with glioblastoma multiforme.
There are a couple of questions left unanswered by this trial, according to Howard A. Fine, M.D., of the National Cancer Institute's Center for Cancer Research. For example, he said, it is unclear whether the survival benefit arose from the low-dose temozolomide given during radiation, from the post-radiation temozolomide that was given for six months, or from both. Previous studies of other chemotherapy drugs had found a benefit only from post-radiation chemotherapy, but this trial was not designed to answer that question for temozolomide.
Comment
The trial demonstrates that temozolomide used during and after radiation is effective as a first-line treatment of the disease. "The findings will probably change the standard of care," said Stupp, an assessment with which Fine agrees. However, said Fine, "we have a long way to go" in developing clearly superior treatments for patients with this difficult disease.
Note: The results of a related study, published in the December 2005 issue of Lancet Oncology, showed that adding temozolomide to radiation treatment did not have a negative effect on the patients' quality of life (see the journal abstract).
 Back to Top |
