- PORTLAND, Or. (UPI) Gleevec,
nicknamed the "leukemia pill" and heralded last year for its
dramatic effectiveness against chronic myelogenous leukemia, or CML, has
demonstrated its powers against a second, previously hopeless cancer, an
international team of researchers reports.
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- The researchers, who collaborated from sites in Boston,
Philadelphia, Portland and Finland, treated 147 patients with advanced
or metastatic gastrointestinal stromal tumor, or GIST. After 9 months or
more of continuous treatment, tumors shrunk significantly -- by 50 percent
to 96 percent -- in more than half of the patients. The tumors stopped
growing completely in another 28 percent, but 14 of the patients died.
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- Ordinarily, unless GIST tumors can be removed surgically,
patients die within 12 to 18 months.
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- "This is what we hope to be the first of many targeted
therapies," said Dr. Brian Druker, a study co-author and JELD-WEN
Chair of Leukemia Research at the Oregon Health & Science University
School of Medicine in Portland.
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- "This is a remarkable success story in the treatment
of cancer," Druker told United Press International. Druker collaborated
with Novartis Pharmaceuticals, of Basel, Switzerland, in the development
of Gleevec.
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- This second success by Gleevec, the first drug aimed
at a small molecule to fight cancer, "validates the idea that discovering
the things in cancer that drive the cancer's behavior is the way of the
future," Dr. Rick Van Etten, associate professor of genetics at the
Center for Blood Research at Harvard Medical School in Cambridge, Mass.,
told UPI. Van Etten was not associated with the study.
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- No patient responded completely to the treatment, Van
Etten noted, probably because numerous mechanisms in solid tumors have
gone awry. Gleevec provides a partial solution, not a cure, he said.
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- The drug works by slinging a precise arrow at a specific
aberrant kinase or enzyme -- called KIT, in the case of GIST -- thereby
shutting down the out-of-control tumor growth. KIT is very similar to another
abnormal protein, BCR-ABL, which Gleevec disables in CML.
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- Gleevec also has shown promise against a third protein,
PDGFRB, involved in chronic myelomonocytic leukemia, or CMML, with minimal
side effects, researchers said.
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- The study is "extremely well done," Charles
Sawyers, professor of medicine at Jonsson Comprehensive Cancer Center at
the University of California at Los Angeles, told UPI. The study's authors
"are the world's experts on this disease," Sawyers said, "So
it's the definitive study."
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- Not all patients in the GIST study responded to the drug,
however, Sawyers said. About 14 percent exhibited early resistance. Sawyers,
who has researched resistance to Gleevec in CML, said a change in a key
kinase, ABL, is one cause of acquired resistance. The ABL morphs into a
slightly different protein, he explained, either through genetic shifts
or mutations at the site where Gleevec binds to the tumor, and the tumor,
no longer crippled, begins begin growing again.
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- The researchers said they also are testing Gleevec with
small cell lung cancer.
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- The study is reported in the Aug. 15 issue of the New
England Journal of Medicine.
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- Copyright © 2002 United Press International. All
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