Toremifene |
Tamoxifen-like |
Breast cancer treatment |
Fewer genotoxic effects than tamoxifen [113], bone effects similar to tamoxifen [119] |
FDA approved for metastatic breast cancer |
Heart protection |
Phase II trial (65 women) better than tamoxifen regulating lipid metabolism [121, 122] |
Mastalgia treatment |
Phase II trials (62 and 195 women) effective [126, 127] |
Prostate cancer prevention |
Phase II trial (514 men) decreases prostate cancer incidence [128] |
Relieve side effects of androgen deprivation therapy |
Phase III trial (1,389 men) improves lipid profiles [130] |
Phase III trial (1,392 men) increases bone mineral density [129] |
|
Ospemifene |
Tamoxifen-like |
Vaginal atrophy treatment |
Estrogenic effects on vaginal epithelium that is not observed with tamoxifen or raloxifene [134–136] |
Phase III trial (826 women) relieves vaginal dryness |
Osteoporosis treatment |
Phase II trial (118 women): Comparable to or slightly better than raloxifene [139] |
Phase III trial planned (detail not available) |
Breast cancer prevention |
Inhibits tumor growth in animal models as effective as tamoxifen [140, 141] |
Not available |
|
GW5638 (DPC974) & GW7604 |
Tamoxifen-like |
Breast cancer treatment (2nd line therapy) |
Works as a SERM and as a SERD [148], effective in tamoxifen-resistant tumors [144, 145]; functions as an ER agonist in bone and cardiovascular system but an antagonist in breast and endometrium [142] |
Phase I trial (9 patients who failed first-line hormone therapy) low toxicity [ASCO meeting 2002, abstract 452] |
|
Arzoxifene (LY353381) |
Raloxifene-like |
Breast cancer treatment |
Antiestrogenic in breast and endometrium, estrogenic in bone and lipids [150] |
Phase III trial (200 patients) inferior to tamoxifen [154] |
Breast cancer prevention |
Effective to prevent ER-positive and ER-negative mammary tumors especially in combination with LG100268 [140, 155] |
Phase I trials (50 and 76 women) low toxicity and favorable biomarker profile [156] |
|
Lasofoxifene (CP-336156, Fablyn) |
Raloxifene-like |
Osteoporosis treatment and prevention |
Higher potency than tamoxifen and raloxifene [158]; higher oral bioavailability than raloxifene [160] |
Phase III trial (1,907 women) significantly increases bone mineral density compared to placebo, no endometrial effects, no association with thromboembolic disorder [159] |
Phase III trial to compare with raloxifene (CORAL trial, details not available) |
Vaginal atrophy treatment |
Phase III trail (445 patients) improves vaginal atrophy compared to placebo |
Breast cancer treatment and prevention |
Effects similar to tamoxifen to prevent and treat NMU-induced mammary tumor in rats [163] |
Phase III trial (PEARL trial with 8,556 women), reduces ER-positive breast cancer incidence compared to placebo; slightly decreases major coronary disease risk; reduces vertebral and non-vertebral fractures; increases risks of venous thromboembolic events but not stroke; no endometrial effects [SABCS 2008, abstract 11] |
Heart disease prevention |
|
Pipendoxifene (ERA-923) |
Raloxifene-like |
Breast cancer treatment |
Inhibits tamoxifen-sensitive and -resistant tumors in mice and rats no uterotrophic activities compared to raloxifene [167] |
Phase II trial to treat tamoxifen-refractory breast cancer in postmenopausal women (details not available) |
|
Bazedoxifene (TSE-424 WAY-140424) |
Raloxifene-like |
Osteoporosis treatment and prevention |
Increases bone density with little uterine or vasomotor effects |
Phase III trial (7,492 women) reduces vertebral and non-vertebral fracture incidences, while raloxifene is not effective against non-vertebral fracture [171] |
Phase III trial (497 women) reduces endometrial thickness, unique property among known SERMs [170] |
Breast cancer prevention |
Inhibits estrogen-stimulated breast cancer cells growth [169] |
Not available |
|
Acolbifene (EM-652, SCH57068) & EM-800 (SCH57050) |
Raloxifene-like |
Breast cancer treatment (2nd line therapy) |
Highest affinity for ER, inhibit growth of multiple breast cancer cells in vitro and in vivo [180] |
Phase III trial, less effective than anastrozole to treat tamoxifen-resistance breast cancer, study halted [182] |
Breast cancer treatment (1st line therapy) |
Phase III trial planned [182] |
Breast cancer prevention |
Phase II trial (started in February, 2009) for premenopausal women |
|
CHF4227 |
Raloxifene-like |
Breast cancer and osteoporosis prevention |
Prevents DMBA-induced mammary tumors and preserves bone mass in rats [184, 185]; |
Phase I trials (24 and 56 women) beneficial on bone markers and lipid metabolism; no effects on endometrium; not causing hot flashes |
|
SP500263 |
Raloxifene-like |
Breast cancer and osteoporosis treatment |
Inhibits breast cancer cell growth in vitro and in vivo without stimulating uterine weight gain [188, 189], protects bone in vitro [190] |
Not available |
|
HMR3339 |
Steroidal |
Osteoporosis and cardiovascular disease prevention |
Better than raloxifene to protect cancellous bones [191] |
Phase II trials (96 and 118 and 94 women) better than raloxifene at improving some beneficial cardiovascular markers [192–194] |
|
PSK3471 |
Steroidal |
Osteoporosis and breast cancer prevention and treatment |
Prevents bone loss in vivo, inhibits growth of breast cancer cells in vivo [197] |
Not available |
|
Trilostane (Modrenal) |
ER subtype-selective |
Breast cancer treatment |
Increases estradiol binding to ERβ, increases ERβ expression, partially inhibits estrogen production [214, 215] |
Approved in UK to treat advanced postmenopausal breast cancer after relapse to initial hormone therapy |
Phase III trial (714 women with advanced breast cancer) effective for both ER-positive and ER-negative breast cancer, effective for endocrine therapy-resistant cancer |
Phase II trial for use in premenopausal breast cancer (details not available) |
Prostate cancer treatment |
Phase II trial with hormone-refractory prostate cancer (details not available) |
|
TAS-108 (SR16234) |
Steroidal, ER subtype-selective |
Breast cancer treatment and prevention |
Inhibits growth of tamoxifen- and AI-sensitive and resistant cancer cells in vitro and in vivo; inhibits DMBA-induced tumor growth in rats [216] |
Phase I trials (16 and 15 women) effective and well tolerated [218, 219] |
Phase II trails (145 and 97 postmenopausal women with advanced breast cancer) beneficial effects, well tolerated [SABCS, 2008, abstract 2131 and 2132] |