#96-37

Issued 5/9/96

BROOKHAVEN LAB STARTS SECOND ROUND
OF CLINICAL TRIALS FOR BRAIN TUMORS

Research in collaboration with University Medical Center at Stony Brook

Upton, NY - The U.S. Department of Energy's Brookhaven National Laboratory, in collaboration with the University Medical Center at Stony Brook, has begun a second round of clinical trials of an experimental treatment for brain tumors.

Called boron neutron capture therapy, or BNCT, the treatment is being tried on glioblastoma multiforme, an especially virulent type of brain cancer that affects about 7,000 Americans each year. Life expectancy of patients with this form of cancer is limited, with fewer than three percent of patients surviving beyond five years.

At present, Brookhaven Lab is the only location in the U.S. where researchers are conducting clinical trials of BNCT on brain tumors. After a single patient was treated at Brookhaven in September 1994, a multi-patient clinical trial was begun in February 1995. Encouraged by results over the past 20 months, Brookhaven researchers are continuing clinicial trials at a higher dose of radiation, under another protocol authorized by the U.S. Food and Drug Administration (FDA). In addition to increased radiation dose, the new protocol has other provisions for improving the effectiveness of the therapy.

BNCT: A Radiation Therapy

In BNCT, a compound containing the element boron is administered intravenously to the patient, in whom it accumulates preferentially in malignant tumor tissue. The tumor is then irradiated with neutrons produced by a nuclear reactor. Some of the boron atoms absorb neutrons and then self-destruct, releasing powerful but very short-range radiation selectively in the tumor.

Because the boron concentrates in the tumor cells, researchers hope that BNCT's selective radiation will control the cancer's growth without seriously affecting normal brain cells nearby.

The second phase of clinical trials will increase radiation dose to tumor in part by either increasing patient exposure time to neutrons or increasing the power of Brookhaven's medical research reactor from 2 megawatts to 3 megawatts. Increasing the radiation dose to the tumor will also increase the dose to normal brain tissue, but this dose is still well within the limits that physicians consider safe for the normal brain.

Also enhancing the radiation dose to tumor is a new collimator, a neutron guide developed at Brookhaven and installed at the reactor. Yet another change in the FDA-sanctioned protocol is an allowance for applying the neutron radiation to two sides of the brain, as is done in all standard radiation therapy. This option will make BNCT more effective for patients with deeper-seated tumors.

Of the 15 patients treated with BNCT at Brookhaven since 1994, eight are still alive. The initial clinical trial proved that the type of BNCT used had no adverse effect on normal brain function and that BNCT delayed tumor regrowth in almost all patients.

In contrast with standard radiation therapy and chemotherapy, which are delivered in multiple sessions over many weeks, BNCT is delivered during a single session. Patient survival following BNCT, as used in the first round, compared favorably with the survival achieved following standard therapy.

Patient Criteria

BNCT is still considered experimental. As a result, Brookhaven's new study is designed to investigate the safety of, identify the potential adverse effects from, and study the effectiveness of the therapy, all at a higher radiation dose. At present, the program is limited to patients with a diagnosis of glioblastoma multiforme.

Patients eligible to participate in the clinical trial must meet certain criteria. At a minimum, they must be at least 18 years old and must never have had radiation, chemotherapy and/or immunotherapy for their brain tumors. Other factors are also considered, such as the tumor's location.

Patients and physicians interested in BNCT can learn more by calling Brookhaven's BNCT Office, at (516)344-3684.

BNCT History

BNCT was first attempted at Brookhaven in the 1950s, and the Laboratory built a small nuclear reactor specifically to test the therapy. Clinical trials at Brookhaven and at another reactor at the Massachusetts Institute of Technology were halted in 1961 because of disappointing results. Boron compounds used at that time did not preferentially accumulate in the tumor. Also, the low-energy neutron beam did not penetrate deeply enough into the patient's head to control tumor growth without harming surrounding healthy brain tissue. Out of the 63 terminally ill people who volunteered for the treatment, most died of their tumors and some died from radiation-induced damage to their brains.

In recent years, two new developments improved the therapy: a new boron compound, called BPA, and an intermediate-energy neutron beam, called an epithermal neutron beam. The new combination was very successful in animal studies, leading Brookhaven researchers to reinvestigate BNCT in clinical trials with humans.

BNCT is also being studied in Japan, where a limited number of patients are treated each year. Researchers in Boston and Europe are also working on BNCT for brain tumors, although they have not yet applied the therapy to humans.

The BNCT program at Brookhaven is funded by the Office of Health and Environmental Research, within the U.S. Department of Energy's Office of Energy Research.

Brookhaven National Laboratory carries out basic and applied research in physical, biomedical and environmental sciences and in selected energy technologies. Associated Universities, Inc., a nonprofit research management organization, operates the Laboratory under contract with the U.S. Department of Energy.

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