Topical tamoxifen benefits cyclic mastalgia.(GYNECOLOGY)

SAN ANTONIO--Afimoxifene, a novel tamoxifen gel applied directly to the breasts, performed favorably as topical therapy for moderate to severe cyclic mastalgia in premenopausal women in a phase II clinical trial.

Although the topical antiestrogen's developer, ASCEND Therapeutics Inc., plans to seek an initial indication for cyclic mastalgia, there also is strong interest in developing afimoxifene as a treatment for male gynecomastia as well as for breast cancer chemoprevention, Dr. Amit Goyal said at the San Antonio Breast Cancer Symposium.

Afimoxifene is 4-hydroxytamoxifen, a highly potent metabolite of tamoxifen, in a proprietary hydroalcoholic gel. Its binding affinity for the alpha and beta estrogen receptors is two- to threefold greater than that of estradiol, explained Dr. Goyal, a surgical oncologist at Cardiff (Wales) University.

Oral tamoxifen, bromocriptine, danazol, and progestins have demonstrated efficacy in treating cyclic mastalgia; however, their systemic side effects render them poorly suited for long-term treatment of a chronic problem.

In contrast, transdermal afimoxifene is highly effective within the breast yet has very low systemic levels, thus reducing the risk of systemic toxicities, he continued.

In a pharmacokinetic study, 16 healthy premenopausal women applied 4 mg of afimoxifene to their breasts daily for 21 days.

At steady state, achieved after 2 weeks of therapy, mean plasma 4-hydroxytamoxifen levels were just 1/18 of those measured in 19 healthy controls taking 20 mg/day of oral tamoxifen.