A phase II trial of Afimoxifene (4-hydroxytamoxifen gel) for cyclical mastalgia in premenopausal women.

Background: Many women experience symptoms of cyclical mastalgia, such as breast pain, tenderness, and nodularity. Tamoxifen and other drugs have been used to alleviate cyclical mastalgia symptoms; however, their use is associated with potentially serious side effects. The current study compared the safety and efficacy of two doses of a topical gel containing 4-hydroxytamoxifen (Afimoxifene, formerly known as 4-OHT) with placebo gel for the treatment of moderate to severe cyclical mastalgia.

Methods: Premenopausal women aged at least 18 years experiencing moderate to severe symptoms were randomized to receive placebo, 2 mg, or 4 mg of Afimoxifene daily delivered as a transdermal hydroalcoholic gel for 4 menstrual cycles. The primary efficacy parameter was change in mean pain intensity as measured by the Visual Analog Scale (VAS) for the seven worst pain score days within a cycle from baseline to the fourth cycle.

Results: After 4 cycles of treatment, statistically significant improvements relative to placebo were measured in mean VAS score in the 4-mg Afimoxifene group (-12.71 mm [95% confidence interval, -0.96 to -24.47; P = 0.034]). Patient global assessment of pain, physician's assessment of pain, tenderness on palpation, and nodularity following 4 cycles of treatment were significantly more likely to show improvements in the 4-mg group, compared with placebo (P = 0.010 [pain]; P = 0.012 [tenderness]; P = 0.017 [nodularity]). Overall, Afimoxifene was well tolerated with few adverse events and no drug-related SAE occurred in any group. There were no changes in menstrual pattern or plasma hormone levels and no breakthrough vaginal bleeding in patients treated with Afimoxifene.

Conclusion: After 4 months of treatment, daily topical breast application of Afimoxifene resulted in statistically significant improvements in signs and symptoms of cyclical mastalgia across patient- and physician-rated scales with excellent tolerability and safety.