Breast-cancer drug to get Europe trial Called 4-OHA, drug discovered by UM scientist.

August 16, 1991|By Sue Miller | Sue Miller,Evening Sun Staff

An experimental drug discovered by a University of Maryland scientist that can buy up to a year of pain-free life for women with advanced breast cancer is expected to be licensed within the next month in England and elsewhere in Europe.

"It seems that it has taken forever," says Dr. Angela Brodie, a Baltimore campus pharmacologist and biochemist whose search for a compound that would block estrogen production began 15 years ago.

"But, I'm excited that we've proved that this drug works," Brodie said. "Breast cancer is a real tragedy and the leading cause of cancer death for women between the ages of 35 and 55."

The drug, known as 4-hydroxyandrostenedione or 4-OHA, can buy up to a year of pain-free life for women who have not responded to or relapsed from tamoxifen, the drug of choice for the majority of post-menopausal women. The 4-OHA shrinks tumors and the patient goes into remission.

While 4-OHA blocks the production of estrogen, tamoxifen blocks the action of estrogen so that when cancer cells attach to it, they don't grow, and that is where the cancer stops. Seventy percent of post-menopausal women with cancer are "estrogen receptor positive," meaning that their cancer cells use the body's estrogen to multiply.

The drug 4-OHA, which can be injected once every two weeks or taken daily in pill form, blocks the enzyme aromatase as well as estrogen production in a variety of sites in the body.

"The 4-OHA inhibits the enzyme, aromatase, and prevents it from making the estrogen that stimulates the tumors," Brodie explained.

The drug has been developed and is being marketed by Ciba-Geigy, one of the world's foremost pharmaceutical firms, which contends that as many as a half a million women could benefit from 4-OHA in England by 1996.

The drug is being licensed in England because that is where most of the clinical trials have been conducted by Brodie's collaborator, Dr. Charles Coombes, an oncologist.

Brodie, who did all of the basic research, testing a variety of compounds for aromatase inhibition with rats, hopes 4-OHA also will be approved by the U. S. Food and Drug Administration within the next two or three years.

Findings from early studies, showing that in 30 percent of the patients the drug shrinks tumors to at least half their size or eliminates them, have held up over the years in continuing larger trials, Brodie said.

"Thirty percent may not sound like much, but it really is a lot when you consider these patients have already advanced in their disease and been treated with other drugs," she said. "And, because 4-OHA is non-toxic, it is very well tolerated."

The collaborative work between UM's Brodie and Coombes has created interest in aromatase inhibitors and now several other drug companies have started to develop a lot of compounds that are "cousins" to the one Brodie discovered.

"We have not found a cure for breast cancer," Brodie says of her discovery. "I want to make that clear. And, we do not have any 4-OHA trials going on right now in this country. But, other researchers at the University of Maryland Cancer Center are conducting trials using a compound, Fadrosole, which, like 4-OHA, is an aromatase inhibitor."

While Fadrosole acts in fairly much the same manner as 4-OHA, it's just slightly different chemically, according to Dr. Jeffrey Abrams, an associate professor of medicine and oncology at the UM Cancer Center. It causes few side effects.

Abrams said he has a double blind study under way that is testing Fadrosole against Megace, the drug that is currently used as second line hormonal therapy for breast cancer. In a double blind study, neither the patient nor the researcher know who is getting which drug.

Abrams is enrolling pre-menopausal and post-menopausal women who have breast cancer that has spread and whose disease has progressed despite surgery and tamoxifen therapy. It's a multi-center trial that will study more than 100 women over the next year. Those interested, should call 328-7904 and ask to speak to the referral coordinator.

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