Boron Neutron Capture Clinical Trials to Treat Glioblastoma Multiforme

Brookhaven National Laboratories, Upton, NY

2/22/95

The U.S. Department of Energy's Brookhaven National Laboratory has begun a multi-patient clinical trial of an experimental treatment for brain tumors.Called boron neutron capture therapy (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 is limited, with fewer than three percent surviving beyond five years. Under a U.S. Food and Drug Administration protocol, Brookhaven will administer BNCT to a total of 28 patients, and the trial is expected to take several months to complete. Collaborating with the Laboratory on this project is Beth Israel Medical Center, in New York City.

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 low-energy neutrons produced by a nuclear reactor. Some of the boron atoms absorb neutrons and then self-destruct, releasing powerful but very short-lived radiation selectively in the tumor. Because the boron concentrates in the tumor cells, researchers hope that the cancer can be destroyed without the radiation seriously affecting normal brain cells nearby.

BNCT History

BNCT was pioneered 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 the results were disappointing. The boron compound 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 destroy the tumor without harming surrounding healthy 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 have improved the therapy: a new boron compound, called BPA, and an intermediate-energy neutron beam, called an epithermal neutron beam. The new combination has been very successful in animal studies, leading Brookhaven researchers to try again using BNCT in clinical trials with humans.
In September 1994, Brookhaven and Beth Israel treated one patient with BNCT, under a single-patient FDA protocol. Although that patient cannot be considered cured, so far the tumor appears to show no sign of regrowth. Brookhaven researchers, however, say that conventional radiation can also stop tumor growth initially, so the patient's condition must be viewed with caution until more time has passed.

BNCT is also being studied in Japan, where a limited number of patients are treated each year in an experimental program. Researchers in Europe are also working on BNCT, although they have not applied the complete therapy to humans. In both Japan and Europe, the boron compound being used is BSH. Brookhaven's research with animals has shown BSH to be less effective than BPA in enhancing radiation dose to tumor tissue.

The Clinical Trial at Brookhaven Lab

Because BNCT is considered experimental, Brookhaven's multi-patient study is designed to establish the safety, potential adverse effects and effectiveness of the therapy.

Patients eligible to participate in the clinical trial must meet certain criteria. At a minimum, they must be age 50 or over and must never have had any form of radiation or chemotherapy for their brain tumors. Other factors are also considered, such as location of the tumor.
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.