Cancer Drug Gleevec Can Interfere With Bone Growth

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From Forbes

Cancer Drug Gleevec Can Interfere With Bone Growth

05.10.06, 12:00 AM ET

WEDNESDAY, May 10 (HealthDay News) -- Gleevec, the drug that has brought

life and hope to patients with some otherwise untreatable cancers, can

interfere with bone formation, researchers have found.

It's a side effect, they say, that deserves careful watching but should not

stop use of the medication.

" This is a new type of side effect that we discovered in part because some

of our patents on Gleevec developed low levels of serum phosphate, a mineral

important in bone synthesis and modeling, " said Dr. Ellin Berman, a member

of the leukemia service at Memorial Sloan-Kettering Cancer Center in New

York City. She's also lead author of a paper on the finding that appears in

the May 11 issue of the New England Journal of Medicine.

" In some patients it developed very quickly, " Berman said. " In some

patients, phosphate levels were very, very low. Then we brought in kidney

specialists and then bone specialists. What we found was surprising. It had

not been described before. "

The patients were being treated for chronic myelogenous leukemia (CML), a

blood cancer whose outlook has been transformed by Gleevec. The drug has

changed the potential life expectancy of CML patients from a few years to

perhaps decades.

The detection of the drug's effect on bone means patients being treated with

Gleevec for either CML or intestinal cancers called gastrointestinal stromal

tumors " have to be screened for abnormalities of bone, " Berman said. " What

Gleevec appears to do is inhibit bone synthesis and bone remodeling. "

The new finding focused on just 16 patients who were found to have low serum

phosphate levels, and its ultimate importance has yet to be determined,

Berman said. " This suggests that Gleevec may have long-term effects on bone,

not bone marrow but bone structure itself, " she said. " We are trying to put

the entire picture together. Is everyone on Gleevec at risk, or just some

people? Do we need to look at the entire bone structure? "

But doctors at Memorial Sloan-Kettering are continuing to use Gleevec --

with careful monitoring of bone structure and function. " Bone is a dynamic

organ, which is constantly being made and remodeled, " Berman said.

Dr. Marshall Lichtman, executive vice president of research and medical

programs at the Leukemia and Lymphoma Society, called the Sloan-Kettering

report " an important observation. It certainly will be helpful for

physicians caring for patients with CML. But what we don't know yet are the

implications of this over the long run. "

Side effects such as the one reported now " are probably predictable, because

we are inhibiting enzymes in normal tissue as well as diseased tissue, "

Lichtman said. " The remarkable thing is how well-tolerated this drug is,

considering that it inhibits the action of critical enzymes. "

Only mild side effects of Gleevec have been reported before, such as

gastrointestinal upset and slight protrusion of the eyes. While the ultimate

impact of the newly reported effect is unknown, " we have to take steps to

prevent any long-term significant bone disease, " Lichtman said.

Berman said there may even be a positive side to the discovery. " Gleevec may

have a role in disease where bone synthesis and turnover need to be turned

off, " she said. For example, it could be helpful when cells from a cancer

elsewhere in the body move into a bone. Stopping bone synthesis could help

control that problem, she said.

More information

To learn more about Gleevec, visit the U.S. Food and Drug Administration

<http://www.fda.gov/cder/drug/infopage/gleevec/default.htm> .