Issued 2/18/99

Contact: Kara Villamil, 516-344-5658 or Mona S. Rowe, 516-344-5056



Encouraging initial results, clinical trial report presented at national meeting

UPTON, NY - More than 400,000 Americans with advanced-stage bone cancer may one day find non-sedating relief for their excruciating bone pain - and possible treatment for their cancer - in a promising therapy now being tested in a nationwide clinical trial.

The newly patented nuclear medicine therapy, based on a compound called tin-117m DTPA, was developed at the U.S. Department of Energy's Brookhaven National Laboratory.

"In preliminary clinical trials involving 47 patients, we showed that it totally or significantly eased the pain of more than 75 percent of patients, relief that lasted for up to a year and produced no side effects," said Brookhaven scientist Suresh Srivastava, co-developer of the therapy.

Srivastava presented those findings and an outlook for the therapy's future today at the American College of Nuclear Physicians' annual scientific meeting in Hawaii.

He also described the current nationwide clinical trial, designed to test the compound's potency in giving pain relief to patients whose cancer has spread to the bone.

Diatide Inc., a New Hampshire biotechnology company that has licensed the technology from BNL, is sponsoring and coordinating the multicenter trial, which will include 100 prostate cancer patients and 75 patients with other cancers. Patients are still being accepted at the participating hospitals, and may call Diatide at 603-621-7574 for more information.

"Based on this promising start, we're now investigating whether our approach may actually help shrink cancer lesions that have spread to the bone, in addition to relieving the pain they cause," Srivastava said. "And, we're pursuing preliminary research on its use in treating primary bone cancer and rheumatoid arthritis."

A New Option for Bone Cancer Pain

Bone cancer is a dreaded secondary result of many primary cancers, arising when tumor cells spread, or metastasize, through the bloodstream to the bones. It strikes 60 to 80 percent of all prostate and breast cancer patients, causing severe pain in more than 75 percent of patients.

Conventional treatments include strong sedatives, which decrease quality of life, hormonal treatments, and radiation therapy that treats only single lesions and requires repeated doses.

Several radio-pharmaceuticals, or short-lived radioactive drugs, have also been approved by the U.S. Food & Drug Administration for bone cancer pain. One of these products, called Metastron, is being used in the clinical trial of tin-117m DTPA to allow comparison of the effects of the two drugs.

In the early 1990s, BNL scientists began developing tin-117m DTPA as a possible addition to the arsenal of radiopharmaceuticals for bone cancer pain relief. They used the Lab's High Flux Beam Reactor research facility to turn regular tin (tin-117) into its isotope tin-117m, then attached the DTPA (diethylenetriaminepentaacetic acid), which helps the tin reach the bone without being sidetracked by interactions with the blood or being taken up into soft tissue. After initial tests, the researchers assessed the therapy in animals and then in human patients in the initial clinical trial.

In the initial clinical trial, the Brookhaven researchers found that the tin-117m targets only the bone, sparing the marrow and soft tissue, but still delivers a highly localized dose of electrons to the tumors to ease pain without sedation. Because it also emits a weak gamma ray, it allowed physicians to use sophisticated imaging equipment to pinpoint where in the body it had traveled.

Srivastava's co-inventors are George Meinken, Harold Atkins and Leonard Mausner. The U.S. patent on this invention was issued in December 1998 to Brookhaven Science Associates, which manages and operates BNL under contract with DOE.

Clinical Trial Guidelines

The new Diatide clinical trial aims to give more information about how well tin-117m DTPA works against bone cancer pain, and to compare it directly with Metastron.

In order to participate in the study, patients must have no substantial damage to their bone marrow as a result of their cancer, as well as no bone fractures. They cannot have had radiation therapy for one month, and cannot have taken Metastron or other radiopharmaceuticals in the three months before receiving the tin. Also, they may not have surgery planned.

Prospective patients are screened via a bone scan that shows physicians the location of their tumors, and a questionnaire asking them to indicate the areas of their body where they feel pain. The two are compared to make sure they correlate.

Patients in the trial receive a one-time intravenous dose of either the tin compound or Metastron, and keep a daily diary of the effect on their pain for 12 weeks afterward. They also track their use of narcotic and non-narcotic pain killers and are examined several times by a physician. Both pain relief and any toxicity to bone marrow are being gauged.

Patients receiving tin-117m DTPA during the trial are being given one of three doses, either one of the two amounts used in the previous BNL studies or a higher dose. Patients receiving Metastron receive the approved therapeutic dose.

The U.S. Department of Energy's Brookhaven National Laboratory creates and operates major facilities available to university, industrial and government personnel for basic and applied research in the physical, biomedical and environmental sciences, and in selected energy technologies. The Laboratory is operated by Brookhaven Science Associates, a not-for -profit research management company, under contract with the U.S. Department of Energy.

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