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Drug Hikes Rate Of Death In Cancer Cells Only

Columbia Presbyterian researchers have shown that a new drug may be a viable treatment option for slowing tumor growth in men with advanced prostate cancer. The study is the first of its kind to show a significant effect of a new class of drugs that may stabilize progressive, recurrent disease in patients with advanced prostate cancer.

Results will be presented at the annual meeting of the American Urological Association in Atlanta, Ga., today by principal investigator Dr. Erik Goluboff.

According to Dr. Goluboff, assistant professor of urology at Columbia University College of Physicians & Surgeons and Director of Urology of the Allen Pavilion at the Columbia Presbyterian Medical Center of the NewYork-Presbyterian Hospital, evidence indicates that the drug, Exisulind, increases the rate of programmed cell death in cancer cells without damaging normal cells.

"This means that the cancerous cells die and can no longer keep dividing and multiplying, which stops the cancer from growing."

Exisulind is from a new class of compounds called selective apoptotic anti-neoplastic drugs (SAANDs). SAANDs inhibit cyclic GMP phosphodiesterase and selectively induce apoptosis (programmed cell death) in abnormally growing precancerous and cancerous cells.

Because SAANDs do not induce apoptosis in normal cells, they do not produce most of the adverse reactions or serious side effects normally associated with chemotherapeutic agents used to treat cancer.

"Our study showed that Exisulind can safely and significantly arrest tumor growth with a minimum of side effects," says Dr. Goluboff. "The results provide evidence that the drug may be an effective alternative to current treatment options."

Previous studies in mice showed that Exisulind inhibits the growth of prostate cancer by 80 percent to 90 percent. In a related study of patients, researchers found that the drug also caused regression in the growth of precancerous colonic polyps, a condition that often leads to colon cancer.

This trial followed 96 prostate cancer patients, who already had their prostate glands removed, for 12 months. All had rising prostate-specific antigen (PSA) levels indicating recurrent disease. Half received Exisulind and half were given a placebo. The researchers measured the drug's ability to slow or halt disease progression by following patients' PSA levels. High levels of PSA are associated with more aggressive disease.

Imaging tests were performed before and after the study. All of the men were classified into risk groups with no statistical difference in age, race, and weight.

The study showed a significant decrease in the rate of rise in PSA in patients given Exisulind compared with placebo.

"Research indicates that Exisulind reduced the growth of prostate cancer in men with progressive, recurrent disease, thereby possibly providing long-term disease control with low incidence of side effects otherwise unattainable for this patient group," says Dr. Goluboff.

Almost 185,000 new cases of prostate cancer will be diagnosed in the United States this year. More than 39,000 men will die of the disease, making it the second leading cause of cancer death in men. While prognosis is good when prostate cancer is detected early, advanced disease has no cure.

Available therapies, such as drugs, hormones, radiation or chemotherapy, try to limit spread of the disease and increase survival time by shrinking or stabilizing tumors.

Dr. Goluboff cautions that more research needs to be conducted to determine long-term effects in these patients and in other groups of patients with prostate cancer.

The study was funded by Cell Pathways Inc., developer of the drug Exisulind. - By Carolyn Conway

[Contact: Carolyn Conway]

01-May-2000

 

 

 

 

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