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| |  DG DISPATCH - AAAS: Chemically-Modified Tetracycline Shows Promise In Advanced Kaposi’s Sarcoma By Ed Susman Special to DG News
SAN FRANCISCO, CA -- February 19, 2001 -- A chemically-modified form of tetracycline, Metastat®, appears to have anti-angiogenesis properties and shows promise in treating Kaposi’s sarcoma. According to researchers at the 2001 annual meeting of the American Association for the Advancement of Science here, the drug appears to have clinical impact even though the patients in the Phase I trial had advanced cancer. "We are very excited about this drug," said Dr. Bruce Dezube, associate professor of medicine at Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, Massachusetts, who is testing Metastat, an investigational drug from CollaGenex Pharmaceuticals, Inc., Newtown, Pennsylvania. "We were also pleased that the drug appeared to work the way we expected it to and that there appeared to be few side effects." Dr. Dezube said that, among the 18 patients with scores of disfiguring 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. Two patients had stabilization of their disease during the course of the six-month trial. In one patient, all evidence of cancer vanished. "We biopsied one area where there was a lesion," Dr. Dezube said, "but the pathologist could not find recognizable cancer cells." He said the histological remission has been durable. "Even though the patient had no side effects from the treatment, after one year we took him off treatment," Dr. Dezube said. He said the patient was reluctant to stop taking the medication because it had been so effective in reducing the lesions. The HIV-positive patient has been off medication for about a year and the lesions have not reappeared, he said. More than 60 percent of the patients in the study, including many of those who had dramatic responses, had more than 50 Kaposi’s sarcomas at the start of the trial. 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, DMD, a professor of oral biology and pathology at the State University of New York at Stony Brook. Dr. Golub said that, in its non-antibiotic role, tetracycline is able to inhibit the effect of enzymes known as matrix metalloproteinases (MMP), which attack connective tissue and are associated with diseases such as blood vessel aneurysms, heart disease, diabetes, periodontitis and cancer. Dr. Dezube gave his patients various doses of the experimental MMP -- also called known as COL-3. In the one patient whose Kaposi’s sarcoma disappeared, the tumors began shrinking within a month after starting the once-a-day oral medication. He said several early studies with Metastat are underway or completed. A 70-person, Phase II trial is expected to begin in the Spring, he said.
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