A phase ii trial of afimoxifene (4-hydroxytamoxifen gel) for cyclical mastalgia in premenopausal women

• Published in: Breast cancer research and treatment Vol. 106; no. 3; pp. 389 - 397
• Main Authors: MANSEL, Robert, GOYAL, Amit, LE NESTOUR, Elisabeth, MASINI-ETEVE, Valérie, O'CONNELL, Katharine
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer 01.12.2007; Springer Nature B.V
• Subjects: Adult; Biological and medical sciences; Breast cancer; Breast Diseases - drug therapy; Cancer research; Cancer therapies; Clinical outcomes; Clinical trials; Double-Blind Method; Drug therapy; Estrogen Antagonists - therapeutic use; Female; Gels; Gynecology. Andrology. Obstetrics; Humans; Mammary gland diseases; Medical sciences; Menstrual Cycle - physiology; Middle Aged; Older people; Pain management; Pain Measurement; Tamoxifen - administration & dosage; Tamoxifen - analogs & derivatives; Tamoxifen - blood; Tamoxifen - therapeutic use; Tumors; Colloidal gel; Human; Pain; Premenopause; 4-Hydroxytamoxifen, Afimoxifene; Mastalgia, Cyclical mastalgia, Breast tenderness; Young adult; Phase II trial; Dosage form; Afimoxifene; Mammary gland; Breast pain
• ISSN: 0167-6806; 1573-7217
• DOI: 10.1007/s10549-007-9507-x

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. 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. 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. 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.