Clinical Trial Examines New Treatment for Endometrial Cancer

The University of Texas M.D. Anderson Cancer Center has opened the first clinical trial to study Mifepristone, formerly known as RU 486, as a treatment for specific types of endometrial cancers.

Mifepristone was first approved by the U.S. Food and Drug Administration in September 2000 for use in the termination of early-stage pregnancy. This will be the first study since its approval by the FDA – and only the second ever conducted in the United States – to examine the hormone therapy’s ability to act as an anti-cancer drug.

Led by Dr. Lois M. Ramondetta, assistant professor in M.D. Anderson’s department of gynecologic oncology, the phase II clinical trial is recruiting 37 women whose tumors are progesterone-receptor positive with recurrent and/or advanced endometriod carcinomas or low-grade endometrial stromal sarcomas.

"Recurrent and advanced endometrial cancer is very difficult to treat and even more difficult to cure," said Dr. Ramondetta. "With this trial of Mifepristone, we are offering patients with very few treatment options a new hormonal therapy with potential."

Endometrial cancer is the most common type of cancer of the gynecological tract. American Cancer Society figures show 36,000 new cases were reported in the United States in 2000 and 6,500 women died from the disease.

Dr. Ramondetta said the presence of estrogen and progesterone receptors in endometrial tumors has been shown to correlate directly to a patient’s survival and response to hormonal therapy. Fifty to 60 percent of primary endometrial cancers and the majority of low-grade endometrial stromal sarcomas are estrogen-receptor and progesterone-receptor positive.

Current hormonal therapy treatments Megace, Depo-Provera, and Provera are not always effective, said Dr. Ramondetta.

"The current response rate to hormonal therapy for women with progesterone-receptor positive advanced or recurrent endometrial carcinoma is 18 to 25 percent. Another 20 to 50 percent show stabilization of disease," said Dr. Ramondetta. "Similarly, patients with low-grade endometrial stromal sarcoma tumors respond to current hormonal therapy options at a rate of 33 to 45 percent.

"By binding the progesterone receptors more powerfully than progesterone, we believe that Mifepristone shows promise for treating these specific types of endometrial tumors," Dr. Ramondetta continued. "Should Mifepristone prove successful in this trial, there is potential for further studies in endometrial cancer, as well as other hormone-associated cancers, such as ovarian, prostate and breast."

Prior to FDA approval, very few studies had been conducted with Mifepristone for alternative medical applications.

Still, said Dr. Ramondetta, the hormone therapy’s potential is impressive. Mifepristone has shown promise shrinking uterine fibroids and treating endometriosis. Small, limited trials have studied Mifepristone as a cancer therapy. A trial with Mifepristone and ovarian cancer was conducted in Camden, New Jersey. Three studies outside of the United States examined the drug in patients with metastatic breast cancer. All studies showed measurable response.

"Not only will this be the first time since its approval by the FDA that Mifepristone will be studied as a cancer therapy, but it will also be the first time that the drug is administered in volume at lower doses to patients, rather than one pill at a time," said Dr. Ramondetta.

M.D. Anderson’s nonrandomized study will involve participants taking one 200-milligram Mifepristone pill a day. Throughout the trial, participants will receive physical exams and CAT scans at specific intervals to evaluate the size of the endometrial tumors. To further evaluate Mifepristone’s effect on tumors, patients may elect to undergo a biopsy two to three months after beginning treatment.

Mifepristone is manufactured by Danco Laboratories. Drug cost to participants is $500 per month. Follow-up tests, including blood-work and X-rays are considered standard, and should be covered by insurance.

Prospective participants and/or referring physicians who would like to learn more about the study, as well as additional inclusion requirements, should call (713) 794-1422 or the M.D. Anderson Information Line at (800) 392-1611. For more information about the clinical trial, visit http://www.mdanderson.org/mifepristone.

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