Research looks at new uses for mifepristone

With mifepristone now approved in the United States for use in early medical abortion, researchers are moving forward in investigating the drug for other areas of women’s health, including contraception and treatment of endometrial cancer.

The Houston-based University of Texas M.D. Anderson Cancer Center has opened the first clinical trial to study the drug’s potential endometrial cancer-fighting capabilities. The Phase II clinical trial is recruiting 37 women whose tumors are progesterone-receptor positive with recurrent and/or advanced endometrioid carcinomas or low-grade endometrial stromal sarcoma.

On the other side of the globe, a just-published preliminary report of a trial indicates the drug’s potential as an estrogen-free oral contraceptive.1 The study, which involved 98 women in Edin-burgh, Scotland, and Shanghai, China, shows that mifepristone in low daily doses inhibited ovulation and induces amenorrhea in most of the study population.

Marketed in the United States as Mifeprex by Danco Laboratories of New York City, mifepristone offers several potential avenues for exploration, says Eric Schaff, MD, professor of family medicine at the University of Rochester (NY). Developed in 1980, the drug’s ability to block the action of progesterone places it as the first of its kind in the class of anti-progestins.

"I have been working with it since 1996 in different trials, and it is just a tremendous drug," Schaff observes. "There are many potential uses for it, as emergency contraception, contraception, as an anti-cancer medication, anti-stress medication, and treatment for fibroids and endometriosis."

Researchers at the Houston Cancer Center see mifepristone as a promising weapon in the war against endometrial cancer, the most common type of cancer of the gynecological tract. According to the Atlanta-based American Cancer Society, 36,000 new cases were reported in the United States in 2000, and 6,500 women died from the disease.

Recurrent and advanced endometrial cancer is very difficult to treat and even more challenging to cure, states Lois Ramondetta, MD, assistant professor in the center’s department of gynecologic oncology. The center, which has been using the drug for the last few years through a compassionate use agreement, has seen encouraging results.

What does Ramondetta see as the three most encouraging aspects of mifepristone for treatment of this deadly cancer?

  • Mifepristone appears to bind the progesterone receptor more strongly than progesterone, and in certain instances, it can act as a progesterone or anti-progesterone.
  • The drug has been shown to have promising anti-angiogenesis properties.
  • Mifepristone appears to be easier to tolerate than Megace (megestrol acetate, Bristol-Myers Squibb, Princeton, NJ), one of the current hormonal treatments for the cancer.

Early research indicates in vitro cell growth suppression using mifepristone in endometrial cancer cell lines, says Ramondetta.2 Studies performed in France in the 1980s in patients with breast cancer (whose tumors are also hormone-responsive) showed encouraging response rates with mifepristone treatment; however, they were not prolonged responses.3

"What was noted, however, is that those patients whose tumors were progesterone receptor-positive had better responses," Ramondetta says.

Center researchers are recruiting 37 women of all ages and ethnicities for the mifepristone trial, which will last at least eight weeks. Since the trial is restricted to patients with progesterone receptor positive tumors, only a few of those evaluated are eligible, says Ramondetta. Women will take a daily 200-mg pill dose of mifepristone. (In comparison, the U.S. medical abortion regimen calls for 600 mg of the drug, provided in three 200-mg tablets, followed two days later by two 200-mcg tablets of misoprostol.) Drug cost to participants is $500 per month.

A double-blind, parallel group study in Edin-burgh and Shanghai examined the use of mifepristone as a potential contraceptive in healthy female volunteers ages 18-40. Participants were randomized to receive 2- or 5-mg mifepristone daily for 120 days. Ovarian activity was monitored by measuring urinary steroids, and participants kept a daily diary of menstrual bleeding throughout the study. Ninety women completed the study.

The drug’s anti-progesterone effect completely prevented ovulation in most women. In Edinburgh, 65% of the 2-mg group were amenorrheic throughout the 120 days of treatment, as were 88% of the 5-mg group. In Shanghai, 90% of women in both groups were amenorrheic. Women who did bleed reported a reduction in the amount of bleeding compared to their normal menstrual period, state the researchers.

Larger clinical studies are need to confirm the safety and effectiveness of this as a potential method of contraception. Research indicates the drug also holds promise as a emergency postcoital contraceptive,4 notes Schaff. Its low number of side effects would make it an attractive option, he says.


For more information on Mifeprex, call the Mifeprex hotline, (877) 4-Early Option [(877) 432-7596], or visit the web site,


1. Brown A, Cheng L, Lin S, et al. Daily low-dose mifepristone has contraceptive potential by suppressing ovulation and menstruation: A double-blind randomized control trial of 2 and 5 mg per day for 120 days. J Clin Endocrinol Metab 2002; 87:63-70.

2. Schneider CC, Gibb RK, Taylor DD, et al. Inhibition of endometrial cancer cell lines by mifepristone (RU 486). J Soc Gynecol Investig 1998; 5:334-338.

3. Romieu G, Maudelonde T, Ulmann A, et al. The antiprogestin RU486 in advanced breast cancer: Preliminary clinical trial. Bull Cancer 1987; 74:455-461.

4. Glasier A, Thong KJ, Dewar M, et al. Mifepristone (RU 486) compared with high-dose estrogen and progestogen for emergency postcoital contraception. N Engl J Med 1992; 327:1,041-1,044.