Introduction to toremifene

Toremifene, a triphenylethylene antiestrogen first synthesized in 1981, binds to the estrogen receptor with an affinity about 5% that of estradiol. Its antiestrogenicity/estrogenicity ratio in animal models is about 5 times that of tamoxifen, though it requires somewhat higher doses for full effectiveness, and it is active against breast cancer in animal and cell culture models. It has a long elimination half-life and there are several metabolites, but the principal antitumor activity appears to be due to the unchanged drug. In Phase I and Phase II clinical trials, toremifene has shown good response rates in ER-positive or ER-unknown tumors, and significant responses after failure of tamoxifen or other hormonal or chemotherapeutic regimens, with rare and mild side effects.