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

  • Clinical Trial
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Abstract

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.

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Acknowledgments

Conflict of Interest: R Mansel had full access to all the data in the study and had final responsibility for the decision to submit for publication; A Goyal and K O’Connell have no conflict of interest; E Le Nestour and Valérie Masini-Etévé are full-time employees of Besins International.

Author information

Authors and Affiliations

  1. Department of Surgery, Wales College of Medicine, Cardiff University, Cardiff, CF14 4XN, UK

    Robert Mansel & Amit Goyal

  2. Besins International, Paris, France

    Elisabeth Le Nestour & Valérie Masini-Etévé

  3. Columbia University Medical Center, New York, USA

    Katharine O’Connell

Authors
  1. Robert Mansel
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  2. Amit Goyal
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  3. Elisabeth Le Nestour
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  4. Valérie Masini-Etévé
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  5. Katharine O’Connell
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Consortia

Afimoxifene (4-OHT) Breast Pain Research Group

Corresponding author

Correspondence to Robert Mansel.

Additional information

Afimoxifene (4-OHT) Breast Pain Research Group—Mansel RE (Principal Investigator and International Coordinator) and Fentiman IS (United Kingdom); Halaska M, Kudela M, Strnad P, Zivny J, Simek R, and Sak P (Czech Republic); Wisniewska-Sawicka E, Michalska M, Sirko I, Michalski A, and Haratym-Maj A (Poland); Harvey JA, Westhoff CL, and Hilt DC (USA).

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Mansel, R., Goyal, A., Nestour, E.L. et al. A phase II trial of Afimoxifene (4-hydroxytamoxifen gel) for cyclical mastalgia in premenopausal women. Breast Cancer Res Treat 106, 389–397 (2007). https://doi.org/10.1007/s10549-007-9507-x

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  • DOI: https://doi.org/10.1007/s10549-007-9507-x

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