| Indication |
For the treatment of metastatic breast cancer in postmenopausal
women with estrogen receptor-positive or receptor-unknown tumors.
Toremifene is currently under investigation as a preventative agent for
prostate cancer in men with high-grade prostatic intraepithelial
neoplasia and no evidence of prostate cancer. |
| Pharmacodynamics |
Toremifene is an antineoplastic hormonal agent primarily used in
the treatment of advanced breast cancer. Toremifene is a nonsteroidal
agent that has demonstrated potent antiestrogenic properties in animal
test systems. The antiestrogenic effects may be related to its ability
to compete with estrogen for binding sites in target tissues such as
breast. Toremifene inhibits the induction of rat mammary carcinoma
induced by dimethylbenzanthracene (DMBA) and causes the regression of
already established DMBA-induced tumors. In this rat model, Toremifene
appears to exert its antitumor effects by binding the estrogen
receptors. In cytosols derived from human breast adenocarcinomas,
Toremifene competes with estradiol for estrogen receptor protein. |
| Mechanism of action |
Toremifene is a nonsteroidal triphenylethylene derivative.
Toremifene binds to estrogen receptors and may exert estrogenic,
antiestrogenic, or both activities, depending upon the duration of
treatment, animal species, gender, target organ, or endpoint selected.
The antitumor effect of toremifene in breast cancer is believed to be
mainly due to its antiestrogenic effects, in other words, its ability to
compete with estrogen for binding sites in the cancer, blocking the
growth-stimulating effects of estrogen in the tumor. Toremifene may also
inhibit tumor growth through other mechanisms, such as induction of
apoptosis, regulation of oncogene expression, and growth factors. |
| Absorption |
Well absorbed |
| Volume of distribution |
|
| Protein binding |
Toremifen is primarily bound to albumin (92%), 2% bound to α1-acid glycoprotein, and 6% bound to β1-globulin in the serum. |
| Metabolism |
Hepatic. Mainly by CYP3A4 to N-demethyltoremifene, which exhibits antiestrogenic effects but has weak antitumor potency in vivo. |
| Route of elimination |
Toremifene is extensively metabolized, principally by CYP3A4 to
N-demethyltoremifene, which is also antiestrogenic but with weak in vivo
antitumor potency. |
| Half life |
5 days |
| Clearance |
|
| Toxicity |
Not Available |
