Toremifene

Definition

Toremifene, also known as Fareston, is a synthetic compound similar to estrogen. It mimics the action of estrogen on the bones and uterus, but blocks the effects of estrogen on breast tissue.

Purpose

Toremifene is used as adjuvant hormone therapy immediately after surgery in early stages of breast cancer and also to treat advanced metastatic breast cancer (stages III and above) in postmenopausal women. Postmenopausal women at high risk of developing breast cancer may take toremifene to reduce risk.

Description

Toremifene is similar to tamoxifen in structure and action. Toremifene can be given as sole treatment, but it is often given in combination with other chemotherapeutic drugs.

Toremifene belongs to a family of compounds called antiestrogens. Antiestrogens are used in cancer therapy by inhibiting the effects of estrogen on target tissues. Estrogen is a steroid hormone secreted by granulosa cells of a maturing follicle within the female ovary. Depending on the target tissue, estrogen can stimulate the growth of female reproductive organs and breast tissue, play a role in the female menstrual cycle, and protect against bone loss by binding to estrogen receptors on the outside of cells within the target tissue. Antiestrogens act selectively against the effects of estrogen on target cells in a variety of ways, thus they are called selective estrogen receptor modulators (SERMs).

Toremifene selectively inhibits the effects of estrogen on breast tissue, while mimicking the effects of estrogen on bone (by increasing bone mineral density) and uterine tissues. The former makes toremifene an excellent therapeutic agent against breast cancer. Although researchers are unclear of the precise mechanism by which toremifene kills breast cancer cells, it is known to compete with estrogen by binding to estrogen receptors, therefore limiting the effects of estrogen on breast tissue. Toremifene may also be involved in other anti-tumor activities affecting oncogene expression, promotion of apoptosis and growth factor secretion.

Recommended dosage

Toremifene is taken orally, and the recommended dose is usually 40 to 60 milligrams once a day, although larger doses are sometimes prescribed. If a dose is missed, patients should not double the next dosage. Instead, they should return to their regular schedule and contact their doctor.

Precautions

Toremifene is not recommended for use in children. Women who are pregnant or nursing should not use this drug since it has several side effects that, although rare, can be severe. It is known to cause miscarriages and birth defects. Women are encouraged to use birth control while taking toremifene. However, oral contraceptives can negatively alter the effects of toremifene. Therefore, patients should explore other birth control options.

Great care should be exercised when toremifene is used with warfarin, an anticoagulant, because toremifene can amplify the effects of warfarin, prolonging bleeding times. The result could possibly be fatal. Patients who are predisposed to the formation of thromboembolisms should use toremifene with caution, because toremifene can increase the risk.

Side effects

Although toremifene is usually well tolerated by patients, there are some side effects. About 25% of patients experience side effects such as mild nausea, vomiting, hot flashes, weight gain, bone pain, sweating, and hair thinning which are usually not severe enough to stop therapy. Patients using tamoxifen for long periods of adjuvant therapy may face unwanted effects years into therapy, which warrant discontinued use of the drug. Some of these effects may include increased risk of forming liver carcinoma as well as uterine and ovarian cancer; eye problems such as retinal lesions, macular edema and corneal changes (most resolve themselves after use is discontinued); neurological problems such as depression, dizziness, confusion, and fatigue; and genital problems such as vaginal bleeding, vaginal discharge, and endometriosis.

Interactions

Toremifene can interfere with the anticoagulant drug warfarin, resulting in severe consequences and death. If these two drugs are used together, patients will be monitored closely. Oral contraceptives and estrogen supplements can also interfere with the action of toremifene.

KEY TERMS

Adjuvant

a treatment added to curative procedures such as surgery to prevent the recurrence of cancer

Anticoagulant

an agent preventing the coagulation of blood

Apoptosis

a type of cell death where cells are induced to commit suicide

Granulosa cells

cells that form the wall of the ovarian follicle

Oncogene

a gene whose presence can cause cancer; these genes usually arise through mutation of a normal gene

Ovarian follicle

several layers of cells that surround a maturing egg in the ovary

Thromboembolism

a blood clot that blocks a blood vessel in the cardiovascular system