Originally created 05/27/01

Augusta doctors find alternative cancer remedy



A recently discovered genetic flaw in prostate cancer cells has spawned a potential new treatment in Augusta that appears to be highly effective and might pose few side effects.

Researchers at the Medical College of Georgia and the Augusta Department of Veterans Affairs Medical Centers are so encouraged that they have applied for a patent on the treatment, even though it so far has only been tested on cancer cells in the laboratory. Vijay Kumar, the director of research in the section of urology at MCG, said he hopes to start testing it soon in animals, with the possibility of early clinical trials in human patients.

The treatment utilizes the abortion-inducing drug mifepristone, a powerful anti-progestin also known as RU 486, and a drug called Apo2L/TRAIL, a derivative of an anti-tumor compound called tumor necrosis factor alpha, which is being jointly developed by the biotech companies Genentech and Immunex, Dr. Kumar said.

Previous research at MCG had focused on mifepristone and the breast cancer drug tamoxifen, and that work is continuing in breast cancer, Dr. Kumar said. But against prostate cancer cells, the treatment didn't appear to be very promising, he said.

In work begun at the Mayo Clinic in Rochester, Minn., and continuing now at MCG and the VA, Dr. Kumar had been isolating genes and proteins that become more numerous when the cell turns "immortal," or begins reproducing out of control. Dr. Kumar hopes to publish the findings of work he has done on a specific gene that serves as an early marker that a cell has gone awry.

Apo2L/TRAIL appears to act on certain receptors on the cell, called death receptors 4 and 5, that then begin a cycle that leads to programmed cell suicide or apoptosis. Mifepristone, which works on the progesterone receptor on prostate cancer cells, kills a certain low percentage of prostate cancer cells, Dr. Kumar said. Adding the two together is something else.

"Lo and behold, we went from about 10 percent or 15 percent (killed) up to 57-60 percent, and that is in the first 20 hours or so," Dr. Kumar said, and that is at very low doses of TRAIL. Mifepristone also seems to make vulnerable prostate cancer cells that were otherwise resistant to TRAIL, Dr. Kumar said.

Genentech is in the process of applying to the Food and Drug Administration for permission to begin clinical trials in humans with TRAIL, but it has not decided which cancer it will be applied to first, company spokesman Neil Cohen said. MCG researchers might contact the companies to see whether they are interested in backing the MCG research, Dr. Kumar said.

So far, TRAIL seems to hold the prospect of few side effects, Dr. Kumar said.

"It seems to affect only cancer cells, for whatever reason," he said.

That could hold particular promise for the treatment of localized prostate cancer tumors. The standard treatments of surgery or radiation or both, with and without blocking the hormones the cancer cells often thrive on, come with significant risk of "life-altering" side effects, said oncologist Michael Shlaer of Medical Oncology Associates. Those can range from impotence to hot flashes to incontinence. Coupled with early detection, the chances of surviving five years after treatment have risen from 70 percent in the early '80s to 90 percent now, which can make those side effects all the more troubling for a man in his 50s, Dr. Shlaer said.

"That's a long time to have impotence and urinary incontinence and a lot of the other things these treatments are associated with," Dr. Shlaer said.

The molecular work with cancer is raising hopes that better, more targeted treatments with fewer side effects are coming.

"For the first time, we are putting the bits and pieces together," Dr. Kumar said.

Reach Tom Corwin at (706) 823-3213 or tomc@augustachronicle.com.