Toremifene, sold under the brand name Fareston among others, is a medication which is used in the treatment of advanced breast cancer in postmenopausal women.
[14] Toremifene is approved for the treatment of metastatic breast cancer in postmenopausal women with estrogen receptor-positive or unknown-status tumors.
[16] It also has superior effects on bone mineral density and lipid profile, including levels of cholesterol and triglycerides, compared to tamoxifen.
[5] The risk of dysrhythmias can be reduced by avoiding use in patients with hypokalemia, hypomagnesemia, pre-existing QT prolongation, and in those taking other QT-prolonging drugs.
[15] It has a lower risk of venous thromboembolism (VTE) (e.g., pulmonary embolism), stroke, and cataracts.
[15] The lower risk of VTE may be related to the fact tamoxifen decreases levels of the antithrombin III to a significantly greater extent than either 60 or 200 mg/day toremifene.
[32] Toremifene has been found to have antigonadotropic effects in postmenopausal women,[33] progonadotropic effects in men,[34] to increase sex hormone-binding globulin levels,[33] and to decrease insulin-like growth factor 1 levels by about 20% in postmenopausal women and men.
[1] Concentrations of toremifene increase linearly across a dose range of 10 to 680 mg.[37][38] Toremifene is 99.7% bound to plasma proteins, with 92% bound specifically to albumin, about 6% to β1 globulin fraction, and about 2% to a fraction between albumin and α1 globulins.
[1][2][4] The long elimination half-lives of toremifene and its metabolites are thought to be due to enterohepatic recirculation and high plasma protein binding.
[13] Toremifene is the generic name of the drug and its INNTooltip International Nonproprietary Name and BANTooltip British Approved Name, while toremifene citrate is its USANTooltip United States Adopted Name and JANTooltip Japanese Accepted Name and torémifène is its DCFTooltip Dénomination Commune Française.
[46] In 2007 the pharmaceutical company GTx, Inc was conducting two different phase 3 clinical trials; First, a pivotal Phase clinical trial for the treatment of serious side effects of androgen deprivation therapy (ADT) (especially vertebral/spine fractures and hot flashes, lipid profile, and gynecomastia) for advanced prostate cancer, and second, a pivotal Phase III clinical trial for the prevention of prostate cancer in high risk men with high grade prostatic intraepithelial neoplasia, or PIN.
Results of these trials are expected by first quarter of 2008[47] An NDA for the first application (relief of prostate cancer ADT side effects) was submitted in Feb 2009,[48] and in Oct 2009 the FDA said they would need more clinical data, e.g. another phase III trial.
[49] Ultimately, development was discontinued and toremifene was never marketed for complications associated with ADT or the treatment or prevention of prostate cancer.
[15] A double-blind, placebo-controlled, randomized, 3 year clinical trial of toremifene was conducted using a sample of 1,260 men.
[51] The sponsor, GTx, who designed and managed the study, found 34.7% of the placebo and 32.3% of the toremifene groups had cancer events.
[52] Previous murine studies using transgenic adenocarcinoma of mouse prostate (TRAMP) mice showed toremifene prevented palpable tumors in 60% of the animals.