SR-16234

SR-16234 is a selective estrogen receptor modulator (SERM) structurally different from approved SERM and has been reported to have estrogen receptor (ER) α antagonistic activity and strong affinity with a weak partial agonistic activity to ERβ receptor. SR-16234 showed strong inhibitory effects on transplanted endometrial cysts in the endometriosis model of rat and mouse. In this clinical trial, efficacy and safety of SR-16234 have been evaluated in endometriosis patients.

This trial was an open-label single arm clinical trial. Ten patients with dysmenorrhea and pelvic pain associated with endometriosis and adenomyosis were enrolled in this trial, and received 40 mg of SR-16234 once daily for 12 weeks. The primary endpoint was the visual analogue scale (VAS) of pelvic pain. The secondary endpoints included dysmenorrhea score, pelvic pain score, objective observations (stiffness of Douglas' pouch, limitation of uterine movement, size of ovarian chocolate cysts, thickness of endometrium, and serum CA125 concentration) and safety.

After oral administration of SR-16234 40 mg for 12 weeks, there were statistically significant decreases in pelvic pain VAS, total pelvic pain score, total dysmenorrhea score, stiffness of Douglas' pouch, limitation of uterine movement compared with the baseline values.

The present trial suggested that a selective estrogen receptor modulator could be used for treatment of pain associated with endometriosis for the first time.

This randomized phase II study was intended to identify the optimal dose of TAS‐108, a novel steroidal antiestrogen, for the treatment of breast cancer in postmenopausal Japanese women. The potential clinical effects of TAS‐108 on the uterus, bone, serum lipids, and hormones were also investigated. Postmenopausal women with hormone receptor‐positive metastatic breast cancer who had previously received one or two endocrine therapies were randomly assigned to one of the three possible dose levels of TAS‐108 (40, 80 or 120 mg/day). Oral TAS‐108 was given daily, and the efficacy and safety of the three doses were evaluated. A total of 97 patients (33, 32, and 32 in the 40‐, 80‐, and 120‐mg groups, respectively) were treated with TAS‐108. The clinical benefit rate was 30.3% for the 40‐mg, 25.0% for the 80‐mg, and 25.0% for the 120‐mg group. The 40‐mg group achieved the prespecified target threshold. TAS‐108 at all dose levels was well tolerated and appeared to have no harmful effects in terms of the variables examined in this study. We conclude that the optimal dose of TAS‐108 among the three doses is 40 mg, once daily, for further studies. JAPIC Clinical Trials Information number: Japic CTI – 121754.