A chemically-modified common antibiotic appears to choke off the blood
supply and then dramatically shrink disfiguring tumors associated with
AIDS, researchers say.
Among the first 18 patients with scores of purplish Kaposi's sarcoma tumors
who took doses of chemically modified tetracycline, more than half had
a clinical benefit.
Eight of the patients achieved a partial response, meaning that half of
their tumors shrank or disappeared. In one patient, all the evidence of
the cancer vanished, and could not even be recognized after a biopsy, said
Dr. Bruce Dezube, associate professor of medicine at Beth Israel Deaconess
Medical Center/Harvard Medical School, Boston, Mass.
"We are very excited about this drug," said Dezube at the annual meeting
of the American Association for the Advancement of Science in San Francisco.
His excitement exudes from the fact that in preliminary studies among desperately
ill patients -- more than half of the patients in the study had more than
50 Kaposi's tumors -- rarely are major responses seen; that the patients
appeared to respond to the treatment according to the predicted mechanism
of action; and there were no unexpected side effects and very little adverse
effects at all.
Tetracycline has been used as an antibiotic for generations, but for its
use in Kaposi's sarcoma, the chemical chain that gives the drug its antibacterial
potency is clipped, said Lorne Golub, a professor of oral biology and pathology
at the State University of New York at Stony Brook.
Golub said that in its non-antibiotic role tetracycline is able to inhibit
the effect of enzymes known as matrix metalloproteinases (MMP). MMPs
attack connective tissue and are associated with diseases such as blood
vessel aneurysms, heart disease, diabetes, periodontitis -- and cancer.
Dezube gave his patients various doses of the experimental MMP Metastat,
also called COL-3. In the one patient whose Kaposi's sarcoma disappeared,
the tumors began shrinking within a month after he started taking the once-a-day
oral medication. When the tumors had been gone about a year, Dezube took
the patient off the drug. It's been a year since then and the tumors have
not recurred, he said.
He said an advanced "Phase II" study with Metastat is expected to begin
in the Spring, he said. Maria Ryan, another clinical researcher at Stony
Brook, said that tetracycline inhibits MMP. By doing so, MMP is unable
to create breaks in blood vessel walls that facilitate nourishment and
spread of the cancer.
Unable to get nutrients, the tumor is isolated, starved and dies. Ryan
said her studies with Periostat, a low-dose formulation of a doxycycline,
which is another drug in the tetracycline family, shows that the drug can
slow progression of periodontal disease as well as other diseases.
She said the drug appears to benefit people with connective tissue diseases
in which MMP plays a destructive role. At a 20 milligram daily dose, Periostat
-- which is already marketed for treatment of periodontal disease -- does
not have any effect on bacteria so it will not contribute to creation of
resistant microbes, Ryan said.
"I've had patients on sub-clinical doxycycline for more than four years,
without seeing any side effects," said Ryan, "including the expected side
effect of sun sensitivity. I put all my periodontal patients on it."
Periostat and Metastat are manufactured by CollaGenex Pharmaceuticals,
Inc., Newtown, Pa.
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2001 by United Press International.
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