Afinoxifene effective therapy for cyclic mastalgia.(Gynecology)

SAN ANTONIO -- Topical afinoxifene proved effective for the treatment of cyclic mastalgia and also showed potential for reduction of mammographic breast density in separate phase II clinical trials presented at a breast cancer symposium sponsored by the Cancer Therapy and Research Center.

Afinoxifene is a highly potent tamoxifen metabolite formulated in a topical alcohol-based gel. Applied to the breast, it avoids first-pass liver metabolism, thus resulting in high levels of the antiestrogen in target breast tissue with low systemic exposure.

The result is an agent designed to have a far quicker onset of benefit than oral tamoxifen, which is prescribed for 5 years for chemoprevention--and afinoxifene also is intended to spare women from the side effects of the parent oral drug, including increased risks of venous thromboembolism, endometrial cancer, and hot flashes.

Dr. Robert E. Mansel reported on 130 premenopausal women with a history of moderate to severe cyclic mastalgia who were randomized to 2 mg or 4 mg/day of afinoxifene or placebo for four menstrual cycles in a double-blind multicenter trial. The primary end point was change in breast pain assessed by patients on a visual analog scale from baseline through the fourth treatment cycle. The 4-mg dose significantly outperformed placebo as evidenced by a mean 32-point reduction from a baseline of 72 points on the 0-100 scale vs. reductions of 19 points with placebo and 25 points with 2 mg/day of afinoxifene.

The 4-mg dose also outperformed placebo in the secondary end points of blinded physician-assessed breast pain, nodularity, and tenderness, with 67%-70% reductions being recorded relative to placebo in each of these domains, added Dr. Mansel, who is professor and chairman of the department of surgery at the University of Wales, Cardiff.

Rates of hot flashes, night sweats, and nipple discharge were similar in the three groups. Application site skin reactions occurred in 4% of women on 4 mg/day of the topical ...