Breast Cancer
Afimoxifene
Afimoxifene (4-hydroxytamoxifen or 4-OHT), the active ingredient in Afimoxifene gel, is an estrogen inhibitor that cannot be delivered orally due to high first-pass liver metabolism. Afimoxifene is one of the most active metabolites of tamoxifen – an orally administered, systemic estrogen receptor antagonist that is the most commonly prescribed adjuvant treatment for breast cancer. Tamoxifen was also the first treatment recommended as chemoprevention in women at high risk for breast cancer1,2. (Raloxifene is FDA-approved to reduce the risk of invasive breast cancer in postmenopausal women at high risk.)
Other agents are under evaluation that could reduce the frequency of undesirable side effects noted with tamoxifen. Most significant to the premenopausal population is the premature onset of menopausal symptoms, such as amenorrhea, hot flushes and night sweats. Two of the other most widely known risks with oral tamoxifen therapy are increased risk of thromboembolic events and endometrial cancer, but these serious adverse effects have not been noted in premenopausal women under age 50. Many of the side effects of oral tamoxifen therapy are due to first-pass liver metabolism and high systemic exposure.
The disadvantages of systemic tamoxifen therapy could potentially be overcome by delivering its potent 4-OHT metabolite directly to the breast tissue, and thus avoiding or minimizing systemic exposure.
BHR-Pharma has formulated Afimoxifene gel for transdermal delivery to the breast tissue using Enhanced Hydroalcoholic Gel Technology (EHG™) which enables the percutaneous absorption of certain drugs, such as Afimoxifene, that cannot be delivered orally. Afimoxifene gel is applied daily by the patient to the surface of the breast. In previous clinical trials, Afimoxifene gel has been shown to be biologically active in the breast tissue, while having systemic exposure in the plasma that is nine times lower than that of oral tamoxifen.3 In various studies, women were treated with Afimoxifene gel for up to six months. Afimoxifene gel was generally well-tolerated; headaches were the most common side effect, which were mild and similar across treatment groups. Menstrual cycles and menses were not disrupted over the course of the treatment period and hormonal plasma levels did not change.
1Fisher B, Costantino JP, Wickerham DL, Redmond CK, Kavanah M, Cronin WM, et al. Tamoxifen for prevention of breast cancer: Report of the National Surgical Adjuvant Breast and Bowel Project P-1 study. J Natl Cancer Inst 1998; 90: 1271-88.
2Fisher B, Costantino JP, Wickerham DL, Cecchini RS, Cronin WM, Robidoux A, Bevers TB, Kavanah MT, Atkins JN, Margolese RG, Runowicz CD, James JM, Ford LG, Wolmark N. J Natl Cancer Inst. 2005 Nov 16;97 (22):1652-62.
3 Rouanet P, Linares-Cruz G, Dravet F et al. Neoadjuvant Percutaneous 4-Hydroxytamoxifen Decreases Breast Tumoral Cell proliferation: A Prospective, Controlled, Randomized Study Comparing 3 Doses of 4-OHT Gel to Oral Tamoxifen. 2003 San Antonio Breast Cancer Symposium, Poster Session.
