TAS-108: a novel steroidal antiestrogen.
TAS-108 is a novel steroidal antiestrogen compound that has a strong binding affinity to the estrogen receptor and, in preclinical studies, has antitumor activity against tamoxifen-resistant breast cancer cell lines. Its molecular mechanisms of actions are different from those of tamoxifen and fulvestrant. TAS-108 showed tissue-selective agonist activity in the bone and cardiovascular systems and, in preclinical and phase I studies, did not show any effect on the endometrium. In a phase I study, TAS-108 was well tolerated at doses ranging from 40 to 160 mg/d with no maximum tolerated dose. Toxicities included hot flashes, headache, and nausea and vomiting. The drug has linear pharmacokinetics. In the phase I study, there was evidence of biological antitumor activity, with stable disease noted in several patients. A phase II study is ongoing, and phase III studies are being planned with the drug.
Buzdar
Aman U
AU
University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA. abuzdar@mdanderson.org
D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017321:Clinical Trials, Phase I as Topic; D004958:Estradiol / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D020847:Estrogen Receptor Modulators / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D006801:Humans
D020847:Estrogen Receptor Modulators; C482068:TS 108; D004958:Estradiol