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 containing4-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.
RCT Entities:
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.
Authors: Oukseub Lee; Katherine Page; David Ivancic; Irene Helenowski; Vamsi Parini; Megan E Sullivan; Julie A Margenthaler; Robert T Chatterton; Borko Jovanovic; Barbara K Dunn; Brandy M Heckman-Stoddard; Kathleen Foster; Miguel Muzzio; Julia Shklovskaya; Silvia Skripkauskas; Piotr Kulesza; David Green; Nora M Hansen; Kevin P Bethke; Jacqueline S Jeruss; Raymond Bergan; Seema A Khan Journal: Clin Cancer Res Date: 2014-07-15 Impact factor: 12.531
Authors: Amal A El Daibani; Fatemah A Alherz; Maryam S Abunnaja; Ahsan F Bairam; Mohammed I Rasool; Katsuhisa Kurogi; Ming-Cheh Liu Journal: Eur J Drug Metab Pharmacokinet Date: 2021-01 Impact factor: 2.441
Authors: Matteo Lazzeroni; Davide Serrano; Barbara K Dunn; Brandy M Heckman-Stoddard; Oukseub Lee; Seema Khan; Andrea Decensi Journal: Breast Cancer Res Date: 2012-10-29 Impact factor: 6.466
Authors: Milena Rondón-Lagos; Victoria E Villegas; Nelson Rangel; Magda Carolina Sánchez; Peter G Zaphiropoulos Journal: Int J Mol Sci Date: 2016-08-19 Impact factor: 5.923