Bexarotene

Bexarotene is a prescription drug used for the treatment of cutaneous T cell lymphoma (CTCL). CTCL is a cancer of the T cells, which are a type of white blood cell. In the disease, T cells proliferate and migrate to the skin where they collect and form rashes, plaques, and tumors. Bexarotene is a retinoid; other retinoids include tazarotene and adapalene (Differin). These retinoids interfere with the growth of skin tumor cells. The U.S. Food and Drug Administration approved bexarotene in December 1999.

Other Names

Bexarotene is marketed as Targretin by Eisai.

Uses

Bexarotene is approved to treat the skin complications associated with CTCL in people for whom at least one previous treatment was ineffective. Bexarotene is sometimes used to treat breast cancer and lung cancer, but it is not approved to treat these cancers.

How Bexarotene is Taken

Bexarotene is available in both 75 mg capsules and a 1% topical (on the skin) gel. The recommended initial daily dose of the capsule is 300 mg/m² (per square meter of body surface area). The gel is initially applied to the skin once every other day for a week. The frequency can be increased to once daily, twice daily, three times daily, and finally four times daily according to tolerance. The gel may be effective at any of these application regimens. The gel is only applied to the skin lesions and allowed to dry before covering with clothing.

How Bexarotene Works

The exact mechanism of action of bexarotene is unknown. However, bexarotene binds and activate several types of retinoid X receptors. Once activated, these receptors bind to DNA and initiate transcription, the first step in protein synthesis. The genes that bexarotene turns on control the growth and replication of cells. As a likely result of this action, bexarotene was shown in lab studies to inhibit the growth of some tumor cell lines. It also shrinks tumors in animal models of cancer.

How the Body Affects Bexarotene

After oral administration, peak circulating levels of bexarotene are reached at about two hours. Bexarotene is partly metabolized in the liver by the CYP3A4 enzyme. Most of a dose of bexarotene is eliminated from the body in the feces.

The amount of bexarotene gel absorbed through the skin is variable but low. More bexarotene enters the blood at the high dosage regimens. Even at four applications per day though, very little bexarotene enters the circulation.

Side Effects

Side effects that are associated with oral bexarotene include the following:

• lipid (or fat) abnormalities (elevated triglycerides, elevated total and low-density lipoprotein (LDL) cholesterol and decreased high-density lipoprotein (HDL) cholesterol)
• low levels of thyroid hormone (hypothyroidism)
• headache
• feelings of weakness
• rash
• low white blood cell count (leukopenia)
• low red blood cell and/or hemoglobin levels (anemia)
• nausea
• infection
• fluid accumulation (edema)
• abdominal pain
• dry skin

Bexarotene gel may cause skin-related side effects:

• itching
• rash
• various skin disorders
• pain

Risks and Precautions

Allergic and hypersensitivity reactions could occur in people who are already allergic to other retinoids.

Bexarotene can increase the skin’s sensitivity to sunlight and extremely bright indoor light (called photosensitivity). The risk of skin damage is minimal if exposure to sunlight or artificial ultraviolet light (such as tanning beds) is limited while receiving bexarotene.

Drug Interactions

Many drugs influence the activity of CYP3A4. Becarotene could interact with drugs that influence CYP3A4 activity. The drugs below may increase blood concentrations of bexarotene (and change its effectiveness or safety) by inhibiting its metabolism:

• antifungals (e.g., ketoconazole (Nizoral), itraconazole (Sporanox))
• antibiotics (e.g., erythromycin)
• components of grapefruit juice

Gemfibrozil has been shown to elevate blood concentrations of orally-administered becarotene, likely because of CYP3A4 inhibition.

Some drugs increase the activity of CYP3A4. These drugs have the potential to reduce blood levels of bexarotene. Some of these CYP3A4 inducers include the following:

• phenytoin (Dilantin)
• rifampin
• carbamazepine (tegretol)

Retinoids act like vitamin A. Vitamin A supplements could compromise the safety of bexarotene.

Bexarotene could enhance the action of diabetic medications, resulting in low blood sugar (hypoglycemia)).

Research

More than 85% of patients with early-stage CTCL who were treated for at least one year with bexarotene gel responded to treatment.^[1]

The effectiveness of oral bexarotene was evaluated in a multicenter trial of 94 patients with advanced-stage CTCL.^[2] A partial or complete response was seen in 45% of patients given 300 mg/m² bexarotene and 55% of patients given more than 300 mg/m². The rate of relapse was 36% in patients treated initially with 300 mg/m² bexarotene.

References

1. ↑ BusinessWire. Targretin Gel Achieved 86% Response Rate in Early-Stage CTCL Patients Treated for More Than One Year, Researchers Report At AAD Meeting
2. ↑ Duvic M, Hymes K, Heald P, et al. Bexarotene is effective and safe for treatment of refractory advanced-stage cutaneous T-cell lymphoma: multinational phase II-III trial results. J Clin Oncol. 2001 May 1;19(9):2456-71. Abstract

External Links

FDA: Information Sheet