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Keywords

Brain tumor, glioblastoma multiforme, malignant glioma, temozolomide ³ (Temodar®), Temodar®. (Definitions of many terms related to cancer can be found in the Cancer.gov Dictionary ⁴.)

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

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 ⁶). 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 ⁷.)

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 ⁸).

Glossary Terms

The removal of cells or tissues for examination by a pathologist. The pathologist may study the tissue under a microscope or perform other tests on the cells or tissue. There are many different types of biopsy procedures. The most common types include: (1) incisional biopsy, in which only a sample of tissue is removed; (2) excisional biopsy, in which an entire lump or suspicious area is removed; and (3) needle biopsy, in which a sample of tissue or fluid is removed with a needle. When a wide needle is used, the procedure is called a core biopsy. When a thin needle is used, the procedure is called a fine-needle aspiration biopsy.

Cancer that continues to grow or spread.

A fast-growing type of central nervous system tumor that forms from glial (supportive) tissue of the brain and spinal cord and has cells that look very different from normal cells. Glioblastoma multiforme usually occurs in adults and affects the brain more often than the spinal cord. Also called GBM, glioblastoma, and grade IV astrocytoma.

A study to compare the results of people taking a new treatment with the results of people taking the standard treatment (for example, which group has better survival rates or fewer side effects). In most cases, studies move into phase III only after a treatment seems to work in phases I and II. Phase III trials may include hundreds of people.

After surgery.

A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial.

The percentage of people in a study or treatment group who are alive for a certain period of time after they were diagnosed with or treated for a disease, such as cancer. The survival rate is often stated as a five-year survival rate, which is the percentage of people in a study or treatment group who are alive five years after diagnosis or treatment. Also called overall survival rate.