Investigators Involved in Toremifene Studies Call It a Potentially Safer Antiestrogen

Toremifene (Fareston), the first new antiestrogen agent for treating advanced breast cancer available in the United States in more than 19 years, is as effective as tamoxifen (Nolvadex) in clinical trials and potentially safer, Richard Gams, md, professor of internal medicine and director of hematology/oncology, Ohio State University, said at a teleconference sponsored by Schering-Plough to introduce the recently approved agent.

Available in Finland since 1988 and in other European countries since the early 1990s, toremifene has shown “equal safety and efficacy and lower risk of other complications, especially secondary endometrial carcinoma,” over some 40,000 patient-years of experience in advanced breast cancer, Dr. Gams said.

Although physicians generally consider the increased risk of endometrial cancer with antiestrogen therapy to be relatively small, “women don’t consider it a small risk,” he said.

Result of Rational Research Program
In 1986, the National Cancer Institute (NCI), recognizing the importance of antiestrogens in preventing breast cancer recurrence, suggested adjuvant use of tamoxifen, and a hunt for alternative antiestrogens began. Toremifene resulted from a rational research program conducted in Finland, Dr. Gams said.After being favorably impressed by toremifene’s potential during a 1985 visit to Finland, he directed a large, multicenter clinical trial of the drug in advanced breast cancer.

Toremifene is currently FDA approved for use as first-line treatment for metastatic breast cancer in postmenopausal women with estrogen receptor-positive or -unknown tumors. Pivotal studies for its use as long-term adjuvant therapy in breast cancer are underway.

Lower Carcinogenic Potential
Another speaker at the briefing, Michael DeGregorio, pharmd, associate professor of internal medicine and associate director of experimental therapeutics, University of California, Davis, Cancer Center, said that it is “important to distinguish this drug from tamoxifen.” Dr. DeGregorio collaborated with Dr. Gams on the clinical trial of toremifene.

He said that toremifene is not a “me-too drug” but, rather, a “second-generation” agent, chosen from hundreds of compounds because of differences in its chemical composition that result in an altered metabolic profile. These changes in toremifene metabolism may reduce the carcinogenic potential of antiestrogen treatment.

The potentially lower risk with toremifene showed up in preclinical models and also “was clarified by a World Health Organization review,” he said. Currently, with thousands of women taking the new agent, there is “no documentation to suggest that Fareston is implicated in producing endometrial cancer,” Dr. DeGregorio added.

He said that although the mechanism of tamoxifen-induced endometrial cancer is currently “hotly debated,” the data show “a clear difference in carcinogenic potential between the two drugs.”

Chemoprevention Trials
Clinical trials to study toremifene’s usefulness in chemoprevention are also beginning. Dr. Gams pointed out that “although tamoxifen is an excellent drug that has created a standard of how women can be treated, its carcinogenic potential is a drawback to using it as a chemoprevention agent in healthy women at high risk of breast cancer.”

Dr. DeGregorio commented that the different metabolic profile of toremifene may not only lower its carcinogenic potential but also “may help in preventing cardiovascular disease and bone loss in women receiving chemoprevention for breast cancer.”