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Chemotherapy Offers Some Promise in Treating Brain Tumors

But experts caution the treatment delivers marginal improvements

WEDNESDAY, March 9, 2005 (HealthDay News) -- New research indicates that chemotherapy has a role in treating certain brain tumors in both adults and children.

One study found that adding chemotherapy to radiotherapy treatment reduced the risk of death by 37 percent in adults newly diagnosed with gliobastoma, one of the most common malignant brain tumors. Also, the treatment had few side effects.

Another study found that administering chemotherapy after surgery in children with medulloblastoma had a survival benefit, and also resulted in less brain damage than radiotherapy.

Radiotherapy -- or radiation therapy -- uses an invisible ray or beam to treat tumors. All the studies appear in the March 10 issue of the New England Journal of Medicine.

"This is not curative treatment. It's an incremental advance but basically these patients remain incurable," said Dr. Lisa DeAngelis, chairman of the department of neurology at Memorial Sloan-Kettering Cancer Center in New York City, and author of an accompanying editorial in the journal. "But every little bit is a step in the right direction."

Others feel that chemotherapy represents more of a dead end in treating this type of tumor.

"We can finally say with a certain degree of authority that chemotherapy in addition to brain radiation is the standard of care for patients who have these highly malignant brain tumors, but the devil is in the details and the details are not that compelling," said Dr. Robert Aiken, director of medical neuro-oncology at Beth Israel Medical Center/St. Luke's-Roosevelt Hospital Center in New York City.

"The therapies that are presently being pursued for brain tumors that revolve around chemotherapy are just not very promising," Aiken added. "I think that what is really needed is to engage in a paradigm shift. We really need to look in more creative directions" for treatment options.

Most adults diagnosed with glioblastoma will die within two years, even if they're treated with surgery and radiotherapy. No previous studies had shown any benefit to adding chemotherapy to the mix.

The new study compared radiotherapy after surgery with radiotherapy and chemotherapy after surgery. The chemotherapy was given both at the same time as radiotherapy and after radiotherapy. A total of 573 patients were randomly divided into two groups. After a median follow-up of 28 months, the median survival in the radiotherapy-plus-chemotherapy group was 14.6 months while, in the radiotherapy group, it was 12.1 months. The two-year survival rate was 26.5 percent in the combined group and 10.4 percent in the radiotherapy alone group.

There's a question as to whether that three-month prolongation of life is "biologically meaningful," Aiken said.

One big plus was that there were few side effects. "This is an oral drug and extremely well tolerated so patients really have nothing to lose and everything to gain," DeAngelis said. "It isn't as if there is some big trade-off with drug-related toxicity to get this small incremental benefit."

This is the first large trial to show a benefit to adding chemotherapy, DeAngelis pointed out. Many doctors have known about this treatment option, and have already adopted the regimen.

Not all people benefited from the combined treatment, however. Another study in the journal found that patients whose tumors had a specific characteristic, a methylated MGMT promoter, accounted for most of the benefit seen in the first study. The promoter silences a DNA repair gene so it cannot repair the damage to tumor cells caused by chemotherapy.

"This isn't going to be so readily translated to the local community doctor for a variety of reasons," DeAngelis said. "But it's the first direct clue that we have in this particular disease about things that can impact outcome."

The third study looked at young children with medulloblastoma, the most common central nervous system tumor in children. This type of tumor not only has a poor prognosis but, in this young population, radiation impairs cognitive function in survivors.

This study was the largest one conducted among children younger than 3 years old. In all, 43 children treated with chemotherapy after surgery had good survival rates, and their mean IQ was higher than that of pediatric patients who had received radiation, although lower than healthy controls.

"This basically helps to establish that these children had very good disease control, at least those that didn't have metastases at the time of diagnosis," DeAngelis said.

For Aiken, however, the true promise of treating brain tumors lies elsewhere.

"We may have done the best we can do with the drugs that we have, and now it really requires that we think of more imaginative programs," he said.

More information

Visit the National Cancer Institute for more on brain tumors.

SOURCES: Lisa M. DeAngelis, M.D., chairman, department of neurology, Memorial Sloan-Kettering Cancer Center, New York City; Robert Aiken, M.D., director, medical neuro-oncology, Beth Israel Medical Center/St. Luke's-Roosevelt Hospital Center, New York City; March 10, 2005, New England Journal of Medicine
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