Toremifene

Definition

Medroxyprogesterone acetate (MPA) is used during cancer therapy to stop new cell growth in some cancers. It is also used outside of cancer treatment as a contraceptive. MPA is known by many different brand names in the United States including Amen, Depo-Provera, Provera, Prodasone, and Progeston.

Purpose

MPA is used to treat some advanced, hormone-responsive cancers of the breast, kidney, and lining of the uterus.

Description

MPA is a synthetic derivative of the female hormone progesterone. In healthy women, progesterone plays a major role in preparing the uterus for pregnancy. MPA has been approved by the Food and Drug Administration (FDA), and its use in cancer treatment is usually covered by insurance. Outside the area of cancer treatment, it is used to prevent pregnancy.

Exactly why MPA stops tumor growth is unclear. Many cancerous tumors are sensitive to hormones. It appears that MPA, in some way, changes the hormonal climate of the tumor so that cells stop responding to other hormones and proteins that would normally stimulate their growth. This drug cannot tell the difference between normal cells and cancer cells, so some normal cells are also killed during treatment. But since cancer cells generally grow more rapidly than normal cells, more cancer cells are killed. MPA is considered very effective and relatively non-toxic.

MPA is usually given to women whose breast cancer has returned or whose cancer does not respond to tamoxifen or toremifene. Both drugs are antiestrogens, or agents that antagonize the actions of estrogen. For these women, it is an alternative to the new aromatase inhibiting drugs (anastrozole, letrozole, or aromasin). Aromatase is one of the enzymes involved in steroid biosynthesis. In endometrial cancer (cancer of the uterus), MPA is sometimes used when cancer has spread (metastasized) beyond the uterus or is inoperable.

Recommended dosage

MPA comes as tablets or as a liquid that is given as an intramuscular injection. For breast cancer, it is usually given as a tablet once a day at the same time each day. Occasionally, MPA is given in divided doses that are spaced evenly throughout the day. For kidney and uterine cancer, MPA is usually given as a shot once a week at first, then later once a month.

In 2001, clinical trials were underway testing the use of MPA in women with both breast and endometrial cancer. The selection of clinical trials underway changes frequently. Current information on clinical trials and where they are being held is available by entering the search term "medroxyprogesterone acetate" at the following web sites:

• National Cancer Institute <http://cancertrials.nci.nih.gov> or (800) 4-CANCER

• National Institutes of Health Clinical Trials <http://clinicaltrials.gov>

• Center Watch: A Clinical Trials Listing <http://www.centerwatch.com>.

Precautions

People taking MPA daily should take it at the same time each day. The time of day is unimportant, but the regular spacing of the dose is important.

Women taking MPA should not get pregnant. It is believed that MPA causes birth defects in babies born to mothers who are taking this drug during the first four months of pregnancy.

Side effects

The number and severity of side effects vary widely among people. Not only is it dependent on each person's own unique body chemistry, side effects vary with the type of cancer, the health of the patient, and the other drugs being given. There is no way to predict who will experience side effects of MPA.

among the more common side effects are:

• increased appetite and weight gain

• nausea

• swelling and fluid retention in the hands, legs, and breast

• breakthrough vaginal bleeding

• muscle cramps

• fatigue

• emotional or mood changes

• headaches

A less common, but serious, side effect is the development of blood clots that can lead to heart attack or stroke. People who have a history of clotting problems are not good candidates for using MPA.

Interactions

Aminoglutethimide (Cytadren: an inhibitor of steroid biosynthesis), when given with MPA, decreases the effectiveness of MPA.

KEY TERMS

Endometrial cancer

Cancer of the uterus.

Food and Drug Administration (FDA)

The government agency that oversees public safety in relation to drugs and medical devices, and gives the approval to pharmaceutical companies for commercial marketing of their products.